Science Day
Tuesday, February 15, 2011
Vanderbilt Kennedy Center Science Day
Tuesday, February 15, 2011
10-10:45 a.m.
Morning Beverages Served (Ballroom)
Registration and poster hanging
11 a.m.
Welcome and Opening Remarks
(Board of Trust Room)
Donna Webb, Ph.D., Science Day Chair
Dennis Hall, Ph.D., Vice Provost for Research and Dean
of the Graduate School, Professor of Physics and Electrical
Engineering
Patricia Labosky, Ph.D., Director of Postdoctoral
Affairs, BRET Office; Associate Professor of Cell &
Developmental Biology and Pharmacology
Jonathan Gitlin, M.D., Assistant Vice Chancellor for
Maternal and Child Health, James C. Overall Professor
and Chair of Pediatrics
11:45 a.m.2:15 p.m.
Poster Session
11 a.m.-1 p.m.
Lunch Buffet (Ballroom)
2:15 p.m.
Faculty Research Presentations
(Ballroom)
Presenters of posters assigned to Session 1 will be available
to discuss their posters from 11:45-12:45.
Presenters assigned to Session 2 will be available to discuss
their posters from 12:45-1:45.
(Board of Trust Room)
Keynote Introduction
Louis Muglia, M.D., Ph.D., Edward Claiborne Stahlman
Professor and Vice Chair for Research Affairs in Pediatrics;
Professor of Molecular Physiology and Biophysics;
Associate Director, Vanderbilt Kennedy Center
2:15 p.m.
Keynote Address
Ronald Emeson, Ph.D., Joel G. Hardman Professor of
Pharmacology; Professor of Molecular Physiology &
Biophysics and Psychiatry; Deputy Director, Center for
Molecular Neuroscience
“Prader-Willi Syndrome and the Tyranny of
Evidence”
3 p.m.
Junior Faculty Introduction
Roger Colbran, Ph.D., Professor of Molecular Physiology
and Biophysics
Junior Faculty Presentation
Sarika Peters, Ph.D., Assistant Professor of Pediatrics
“Trajectories of Autism Spectrum Features in
Angelman and Rett Syndromes”
3:30 p.m.
Poster Awards Presentation and
Concluding Remarks
(Board of Trust Room)
Elisabeth Dykens, Ph.D., Annette Schaffer Eskind Chair
and Director, Vanderbilt Kennedy Center; Professor of
Psychology and Human Development, Psychiatry, and
Pediatrics
Wine and Cheese Reception (Ballroom)
4:30 p.m.
Posters removed
Science Day Goals
• To promote “centeredness” by providing a scientific forum for VKC faculty,
their students, and postdoctoral fellows
• To promote interdisciplinary research collaboration
• To provide faculty and trainees with an opportunity to present significant
research findings
75 O'Brien, B. (SN)
66 Barquero, L. (CBI)
58 Henninger, N. (CBI)
50 Shivers, C. (CBI)
42 Peterman, J. (CBI)
34 Fyfe, E. (CBI)
26 Thakkar, K. (SN)
18 Korade, Z. (CMN)
10 Lambert, W. (Core)
2 Allison, J. (Core)
74 Restrepo, N. (CBI)
65 Dankner, N. (CBI)
57 Yoncheva, Y. (SN)
49 Geng, F. (CBI)
41 Laryea, G. (CMN)
33 Sakrikar, D. (CMN)
25 Vazquez, M. (CBI)
17 Litt, M. (CMN)
9 Joosten, Y. (Core)
1 Barrett, R. (Core)
11 Adkins, K. (Core)
3 Henderson, L. (Core)
27 Goodman, M. (CMN)
19 Corbett, B.-SENSE (CBI)
43 Vollbrecht, P. (CMN)
35 Viarouge, A. (SN)
59 Kwakye, G. (CMN)
51 Potts, J. (CBI)
76 Chakraborty, S. (CMN)
67 Avery, S. (SN)
94 Jones, R. (CBI)
85 Armour, E. (CMN)
112 Zurkovsky, L. (SN)
103 Edery Clark, C. (CBI)
CBI — Clinical, Behavioral, and Intervention Research
CMN — Cellular and Molecular Neuroscience
SN — Systems Neuroscience
93 Majumdar,D.(CMN)
84 Erreger, K. (CMN)
111
102 Eckstrand, K. (SN)
92 Griffin, M. (CBI)
83 Doydum, A. (CBI)
110 Fan, R. (SN)
101 GillingMcIntosh, L.(CBI)
12 Ghose, D. (SN)
4 Matthews, R. (Core)
28 Lin, W. (CMN)
20 Hubbard, E. (SN)
44 Starkey, G. (CBI)
36 Martin, J. (CMN)
60 Bichell, T. (CMN)
52 Grier, M. (CMN)
77 Pryweller,J-Sensory(CBI)
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95 Baucum, A.J. (CMN)
86 Koran, M. (CBI)
113 Arnett, M. (CBI)
104 Limpert, A. (CMN)
13 Xu, L. (CMN)
5 Anderson, A. (Core)
29 Hammock, E. (CMN)
21 Varney, S. (CMN)
45 Kwakye, L. (SN)
37 Hawkins, N. (CMN)
61 Scheib, J. (CMN)
53 Downs, L. (CBI)
78 Kraemer, B. (CMN)
69 Wright, A. (CMN)
96 Essex, B. (CBI)
87 Brock, A. (SN)
114 Ulbricht, R. (CMN)
105 Simmons, A. (CBI)
14 Corbett, B.-Peer (CBI)
6 Rosemergy, J. (Core)
30 Lense, M. (CBI)
22 Werfel, K. (CBI)
46 Dang, R. (CMN)
38 Lieberman, R. (CBI)
62 Jorge, B. (CMN)
54 Tidball, A. (CMN)
79 Foss-Feig, J. (CBI)
70 Dunn, M. (CBI)
97 Wills, T. (CMN)
88 ShireyRice, J. (CMN)
115 Kulbaba, G. (CBI)
106 Kruger, J. (SN)
Poster Session
Student Life Center Ballroom
FEBRUARY 15, 2011
15 Moneta, L. (CBI)
7 Key, A. (Core)
31 Edmiston, K. (SN)
23 Ledford, J. (CBI)
47 Kliman, M. (CMN)
39 Conrad, K. (SN)
63 Rentmeester,L.(CBI)
55 Pryweller,J-Effect(CBI)
80 Bronson, S. (CMN)
71 Sawyer, E. (SN)
98 Mayer, J. (CBI)
89 Robinson, K. (CBI)
116
107 Wise, J. (CBI)
VANDERBILT KENNEDY CENTER SCIENCE DAY
16 Clauss, J. (SN)
8 Educ. NS
32 Siller, S. (CMN)
24 Schmidt, M. (CMN)
48 JalanSakrikar,N.(CMN)
40 Kale, A. (CMN)
64 Seay, A. (CBI)
56 Klug, J. (CMN)
81 Fisher, J. (CBI)
72 Borgschulte,C.(CBI)
99 Aboud, A. (CMN)
90 Fan, Q. (CBI)
117
108 Wegrzynowicz (CMN)
82 Clay, H. (CMN)
73 Muller, C. (CMN)
100 Gu, C. (SN)
91 Hardaway,A. (CMN)
118
109 Gordon, R. (CBI)
Vanderbilt Kennedy Center
for Research on Human Development
Who We Are and Who We Serve
The Vanderbilt Kennedy Center has been transforming the lives of children and
adults with disabilities through innovative research, training, and services for 45
years. It is generating new knowledge and training the next generation of
researchers as a national Eunice Kennedy Shriver Intellectual and
Developmental Disabilities Research Center (IDDRC), one of fourteen
supported by the Eunice Kennedy Shriver National Institute of Child Health and
Human Development. The Center conducts training, provides services and
technical assistance, conducts research, and disseminates information in
Tennessee and the Mid-South as a University Center for Excellence in
Developmental Disabilities Education, Research, and Service,
supported by the Administration on Developmental Disabilities. The Center
provides interdisciplinary training through the MIND Training Program, a
Leadership Education in Neurodevelopmental Disabilities Training Program
supported by the Maternal and Child Health Bureau, Health Resources and
Services Administration. The VKC Treatment and Research Institute for
Autism Spectrum Disorders (TRIAD) works to improve ASD assessment and
treatment services for individuals with ASD and their families while advancing
knowledge and training.
One in 5 children has a developmental disability. Examples include autism,
intellectual disability, genetic syndromes, brain or spinal cord injury, and
cerebral palsy. The developmental concerns of Center researchers and clinicians
are broad, including sensory impairments, learning disabilities, behavior
disorders, depression, schizophrenia, and chronic health conditions. In
understanding and treating disabilities, researchers, clinicians and educators
consider individual and family strengths and resources as well as challenges
across the lifespan.
Major Research Areas
Investigators in the VKC IDDRC conduct research within four broad thematic
areas of research:
Basic mechanisms—Scientists study fundamental principles of nervous system
development, strategies of cell signaling and neurotransmission, plasticity and
structure-function relationships through the use of novel invertebrate and
vertebrate model systems. These efforts focus on understanding factors during
fetal development that increase risk for intellectual and developmental
disabilities (IDDs), and pre- and postnatal gene-by-environment factors that
influence nervous system ontogeny and maturation. The relationships between
inherited and acquired neurodevelopmental disorders and long-term dysfunction
also are studied. Translation of basic studies to clinical investigations is done
through unique, collaborative genetic and behavioral studies in model systems
and human populations.
Cognitive processes and interventions—Scientists examine the
development and functioning of circuits and systems that underlie learning and
memory, executive functioning, and attention, from early postnatal periods of
development through adults. Central to this area are multidisciplinary studies
linking projects among various disciplines represented in the VKC, including
special education, psychology, neuroimaging, electrophysiology, and genetics.
Leveraging strengths in special education and developmental psychology, IDDRC
scientists translate research findings on fundamental cognitive processes to
interventions with children, adolescents, and adults with inherited and acquired
disorders that result in IDD and learning disorders.
Mental health and interventions—IDDRC investigators define the
fundamental features of co-occurring mental health dysfunction in individuals
with IDDs and the neurodevelopmental bases of child-, adolescent-, and adultonset mental disorders, including ADHD, anxiety, depression, schizophrenia, and
dementia. VKC investigators have major efforts in identifying the molecular and
cellular basis for the initial wiring and maturation of brain areas involved in
mood and emotion, and the resulting behavioral disorders that occur due to
altered development. Rare and common mutations in candidate genes are
identified in autism, OCD, ADHD, and other neurodevelopmental disorders. The
impact of these mutations on protein function is tested in model systems.
Genetic and environmental contributions to psychopathologies are studied in
animal models and clinical populations. VKC investigators also study
longitudinal trajectories of mental health dysfunction in syndromic IDDs and in
mental illnesses that have a neurodevelopmental basis. Research also includes
prevention in at-risk youth, and biobehavioral interventions.
Life impact—Scientists examine the functional impact, over time, of inherited
and acquired IDDs and health and mental health impact on children,
adolescents, and adults, and their families. Research projects are highly
interdisciplinary, integrating methodological strategies to examine behavioral,
psychological, educational, and medical health outcomes in individuals with
disabilities and the nuclear and extended family members. Research on best
practices to intercede on behalf of families who are most at-risk is performed.
Research Support Services
Vanderbilt faculty affiliated with the Vanderbilt Kennedy Center can access a
wide range of research support services organized into five cores, listed below.
For details on services, consult the Research section of the VKC website
(kc.vanderbilt.edu).
Basic Neuroscience Services (Karoly Mirnics, M.D., Director)
Statistics and Methodology Services (Frank Harrell, Ph.D., Director)
Clinical Neuroscience Services (Adam Anderson, Ph.D., Director)
Participant Recruitment and Assessment Services (Elisabeth Dykens, Ph.D.,
Director)
Administrative Services (Elisabeth Dykens, Ph.D., Director, Tim Stafford,
Administrator)
In the poster sessions, see posters 1-11 describing Core Services.
Taking Part in Research
Babies, children, and adults, with and without disabilities, are invited to be part
of studies. We provide two ways to find out about studies.
StudyFinder
(615) 936-0448
A website listing research projects of VKC Investigators and Members
involving children and adults, with or without disabilities; project may
provide treatment or advance knowledge.
kc.vanderbilt.edu/studyfinder
Research Family Partners
(615) 936-0448
Individuals who register at this website will be contacted when an
appropriate VKC study begins and will be able to choose whether to take
part.
www.kc.vanderbilt.edu/RFP
Vanderbilt Kennedy Center Contacts
Toll-Free & VKC UCEDD (866) 936-VUKC [8852]
General Information (615) 322-8240
Family Outreach (615) 936-5118
Giving (615) 343-4176
Fax (615) 322-8236
kc.vanderbilt.edu
The VKC IDDRC is funded by Grant No. P30 HD15052 from NICHD. The VKC UCEDD is funded
by ADD Grant No. 90DD0595. The LEND Training Program is funded by Grant No. 5 T73 MC
00050, U.S. MCH/HRSA.
In Grateful Appreciation
Vanderbilt Kennedy Center Science Day Faculty Planning Committee
Jennifer Blackford, Ph.D., Assistant Professor of Psychiatry
Roger Colbran, Ph.D., Professor of Molecular Physiology and Biophysics
Ann Kaiser, Ph.D., Professor of Special Education; Susan Gray Chair in
Education and Human Development; Professor of Psychology
Donna Webb, Ph.D., Assistant Professor of Biological Sciences and Cancer
Biology—Committee Chair
Vanderbilt Kennedy Center Staff
Kylie Beck
Sue King
Tony Maupin
Amy Pottier—Special thanks for coordination
Jan Rosemergy
Lori Ryden
Jon Tapp
Courtney Taylor
Nick Williams
Poster Session Faculty Judges (*Chair)
Cellular and Molecular Neuroscience
* Roger Colbran, Ph.D., Professor of Molecular Physiology and Biophysics
Aaron Bowman, Ph.D., Assistant Professor of Neurology
Ana Carneiro, Ph.D., Assistant Professor of Pharmacology
Kevin Ess, Ph.D., M.D., Assistant Professor of Neurology, Pediatrics, and Cell &
Developmental Biology
Maureen Hahn, Ph.D., Assistant Professor of Genetic Medicine/Department of
Medicine and Pharmacology
Elizabeth Hammock, Ph.D., Instructor, Pediatric Endocrinology
Zeljka Korade, Ph.D., Research Assistant Professor of Psychiatry
BethAnn McLaughlin, Ph.D., Assistant Professor of Neurology and Pharmacology
M. Diana Neely, Ph.D., Research Assistant Professor of Neurology
Christopher Olsen, Ph.D., Research Instructor in Molecular Physiology and
Biophysics
Sachin Patel, M.D., Ph.D., Assistant Professor of Psychiatry
Gregg Stanwood, Ph.D., Assistant Professor of Pharmacology
Jeremy Veenstra-VanderWeele, M.D., Assistant Professor of Psychiatry, Pediatrics,
and Pharmacology
Qi Zhang, Ph.D., Assistant Professor of Pharmacology
Clinical, Behavioral, and Intervention Research
* Ann Kaiser, Ph.D., Professor of Special Education; Susan Gray Chair in Education
and Human Development; Professor of Psychology
Daniel Ashmead, Ph.D., Professor of Hearing and Speech Sciences, Associate
Professor of Psychology
Carissa Cascio, Ph.D., Assistant Professor of Psychiatry
Craig Kennedy, Ph.D., Associate Dean for Research, Vanderbilt Peabody College;
Professor of Special Education and Pediatrics
Alexandra (Sasha) Key, Ph.D., Research Assistant Professor of Hearing and Speech
Sciences; Director, Vanderbilt Kennedy Center Psychophysiology Lab
Evon Lee, Ph.D., Associate Professor of Pediatrics; Psychological Assessment
Coordinator, Vanderbilt Kennedy Center Participant Recruitment and
Assessment Core
Bruce McCandliss, Ph.D., Patricia and Rodes Hart Professor of Psychology and
Human Development
Julia Noland, Ph.D., Research Assistant Professor of Psychology
Julie Lounds Taylor, Ph.D., Assistant Professor of Pediatrics and Special Education;
Quantitative Services Specialist and Education Co-Coordinator, Vanderbilt
Kennedy Center Statistics and Methodology Core
Tedra Walden, Ph.D., Professor of Psychology
Paul Yoder, Ph.D., Professor of Special Education
Additional judges to be announced.
Systems Neuroscience
* Jennifer Blackford, Ph.D., Assistant Professor of Psychiatry
Carissa Cascio, Ph.D., Assistant Professor of Psychiatry
Neil Woodward, Ph.D., Assistant Professor of Psychiatry
Bruce McCandliss, Ph.D., Patricia and Rodes Hart Professor of Psychology and
Human Development
Victoria Morgan, Ph.D., Assistant Professor of Radiology & Radiological Sciences
Undergraduate Posters
Ford Ebner, Ph.D., Professor of Psychology and Cell & Developmental Biology
Additional judge to be announced
Attention: Poster Presenters
Thank you for taking part in Vanderbilt Kennedy Center Science Day! All poster
presenters will be appointed as a Vanderbilt Kennedy Center Affiliate. All Affiliates
may compete for VKC Travel Awards.
Vanderbilt Kennedy Center Travel Awards—Eligibility and Application
Process
VKC Travel Awards supplement other funding sources. Applications (letter of
request) will be considered for travel to scientific conferences held through
December 31, 2011. Travel awards will not exceed $250. Travel Awards are available
on a first-come, first-served basis until funds set aside for this purpose are fully
committed.
Eligibility
Graduate students and postdoctoral fellows:
• who are engaged in research with a VKC Investigator or Member
• who are VKC Affiliates (i.e., who presented a poster at Vanderbilt Kennedy Center
Science Day, February 15, 2011)
• who will use the funds to travel to a research conference at which the Affiliate is
making a presentation.
Process
• The VKC Affiliate submits a letter of request, co-signed by the VKC Investigator or
Member with whom the trainee is conducting research. The letter should describe
how the travel award would be used (conference title, location, dates, presentation
title), and how the trainee’s research interests and research training would be served.
• Letter of request should be submitted to Jan Rosemergy, VKC Deputy Director, for
review and decision. (jan.rosemergy@vanderbilt.edu; 322-8238; PMB 40, 230
Appleton Place).
• VKC Communications will notify trainee of decision. If a Travel Award is made,
instructions for payment will be included in award letter.
Attention: Students Attending Science Day
Students often look for positions in research labs or programs, and in turn,
researchers often are looking for interested students to become involved in their
research. We hope you will use VKC Science Day as an opportunity to explore the
range of research in many disciplines, to talk with trainees and faculty engaged in
research, and to identify labs or research programs you may want to contact in the
future.
Poster Abstracts
1. Introducing the Rat Core of the Laboratory for
Neurobehavior
Vanderbilt Kennedy Center Core (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Randy S. Barrett, Ph.D.
Author: Randy S. Barrett, Ph.D.
Vanderbilt University Medical Center (VUMC) has recently built and furnished a state-ofthe-art rodent behavioral testing facility that operates as a core. All investigators at VUMC
and Vanderbilt University have access to this facility which is outfitted with multiple rooms
of equipment for the purpose of behavioral testing in rats and mice. Examples of assays
available for research in rats include models of anxiety, depression, drug abuse, learning and
memory, cognition, attention, social interaction, pain, motor activity and coordination.
Investigators can employ the latest technology in video capture and software-based analysis
of behavior. Additionally, a surgical suite is available, outfitted with a wide variety of
equipment such as standard rat stereotaxic frames and a stereo-microscope, as well as
perfusion tables. Core personnel are available for training and consultation. Housing takes
place inside the facility’s vivarium, which is expected to stay Virus-Antibody free. The
facility is located on the 9th floor of Medical Center North III.
2. The Mouse Neurobehavioral Core
Vanderbilt Kennedy Center Core (Session 2: 12:45-1:45 p.m.)
Presenter: John Allison, Ph.D.
Authors: John Allison, Ph.D., Gregg Stanwood, Ph.D., Danny Winder, Ph.D.
The Murine Neurobehavioral Core provides equipment, training, and consulting for
Vanderbilt personnel to investigate the behavioral phenotypes of transgenic and knockout
mice. The core provides many assays for basic neurological examination, motor
coordination, locomotor activity, anxiety, learning and memory, cognition, sensorimotor
gating, social behaviors, home-cage behaviors, drug abuse, and depression-related
behaviors. The core also has a small surgery suite to use in conjunction with behavior
studies. Many of our methods employ state-of-the-art video capture and software-based
analysis of mouse behaviors. We will present an overview of currently utilized assays and
consultation services available in the core, and information describing our facility, which is
located in the Laboratory for Neurobehavior on the 9th floor of the MCNIII tower.
3. Research Participant Recruitment and Assessment
Services: Supporting Research Teams in Connecting With
Potential Volunteers Vanderbilt Kennedy Center Core (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Lynnette Henderson, Ph.D.
Authors: Lynnette Henderson, Ph.D., Richard Urbano, Ph.D., Evon Lee, Ph.D.,
Robert Crouch, Ph.D., Elisabeth Dykens, Ph.D.
This poster will summarize services available from the VKC Participant Recruitment and
Assessment services (Core E).
The overall objectives of Core E are to provide services that promote the successful
recruitment and initial assessment of research participants, and to provide VKC
investigators with access to epidemiological-based study samples. Specifically, Core E:

Provides VKC investigators with ready access to families and participants with different
types of disabilities by
o
going directly to communities of interest locally and state-wide,
o
using web-based materials, including a research participant registry focused
on several disability groups and
o
planning recruitment strategies appropriate to the population

Offers VKC investigators easy access to epidemiological and longitudinal samples via
State of Tennessee linked administrative databases on demographic and health related
variables (e.g., birth, death, marriage, divorce, hospital discharge)

Provides consultation and training to VKC investigators in psychological, cognitive, and
behavioral assessments

Leads workshops on new assessment tools

Contributes to the accurate diagnoses of children with Autism Spectrum Disorders
(ASD) and supports autism research registry.
The goal of this poster is to summarize these services, and provide examples of their
successful implementation in clinical research conducted by VKC investigators and their
research teams. At the poster session, attendees can meet core personnel and ask questions
about the available services.
4. Cell Imaging Shared Resource
Vanderbilt Kennedy Center Core (Session 2: 12:45-1:45 p.m.) Presenter: Robert Matthews, Ph.D.
Author: Robert Matthews, Ph.D.
The Cell Imaging Core is designed to provide members of the Kennedy Center with access to
state-of-the-art biophysical and imaging technologies. Access means not just availability of
equipment, but also availability of the needed expertise for training, help with data
collection, and assistance with data analysis and interpretation. Available equipment
includes several confocal microscopes, some with live cell imaging capability and one
specialized confocal microscope for capturing images at high (msec) frequency. Widefield
microscopes are also available to do routine fluorescent and bright field imaging as well as
TIRF, calcium ratio imaging and high resolution/low magnification imaging of embryos,
large brain sections and C. elegans. Transmission and scanning electron microscopy have
recently been added to our core facilities. The Core is managed by three internationally
recognized experts, two of whom have also established independent research programs. The
service aspect of the Core is carried out by dedicated employees, but draws upon the
expertise of the research and development components within the research labs. This
strategy allows Kennedy Center researchers access to cutting edge methods immediately
after they are developed. The Cell Imaging Core is part of the Vanderbilt Cell Imaging
Resource, which is available for use by all Vanderbilt University researchers.
5. Neuroimaging Core
Vanderbilt Kennedy Center Core (Session 1: 11:45 a.m.-12:45 p.m.) Presenter: Adam Anderson, Ph.D.
Author: Adam Anderson, Ph.D.
6. Communication and Dissemination Services of the
Vanderbilt Kennedy Center
Vanderbilt Kennedy Center Core (Session 2: 12:45-1:45 p.m.) Presenter: Jan Rosemergy, Ph.D.
Authors: Jan Rosemergy, Ph.D., Amy Pottier, Courtney Taylor, Nick Williams
This poster will provide an overview of services available from VKC Communication and
Dissemination, a part of the VKC Administrative Services Core.
This core service’s overall objectives are to:
• Provide support for communicating research recruitment needs,
• Disseminate research findings,
• Plan and manage research education and research ethics programs,
• Coordinate Center governance and promote Center cohesiveness through the VKC website,
Quick Guide, Discovery newsletter, weekly Monday Morning Message, and activities such as
Science Day.
At the poster session, attendees can meet core personnel and ask questions about the
services available.
7. The Psychophysiology Services EEG/ERP Laboratory
Vanderbilt Kennedy Center Core (Session 1: 11:45 a.m.-12:45 p.m.) Presenter: Alexandra (Sasha) Key, Ph.D.
Authors: Alexandra (Sasha) Key, Ph.D., Dorita Jones, Amber Vinson
The VKC Psychophysiological Services (MRL 227-230) enables VKC members and
investigators to add human electroencephalography (EEG), event-related potential (ERP),
and eye tracking measures to their research programs. The range of research questions
addressed using these methods includes (but is not limited to) documentation of individual
differences in cognitive processes, identification of neural and behavioral markers of risk for
adverse developmental outcomes, and assessment and/or prediction of treatment effects.
The range of services includes experiment design and programming, data collection and
analyses, and training of research personnel. The lab can obtain psychophysiological data
associated with internal and/or external events from two participants at the same time with
no age restriction (from newborns through adulthood). Lab equipment includes two 128electrode EEG systems capable of functioning independently or as a 256-electrode system
ideal for integrating data with other imaging techniques (e.g., fMRI) as well as a portable
128-channel EEG system that can be used to obtain data at off-campus locations (e.g.,
schools, hospitals, residential facilities, etc.). The high-density electrode arrays used in the
lab for EEG/ERP acquisition allow for quick application and removal and, in conjunction
with the high-impedance amplifiers, provide clean electrophysiological data without the
need for skin abrasion, making it a very participant-friendly process, well-tolerated even by
young children and participants with various disabilities (e.g. autism, Down syndrome). Eye
tracking data are acquired using a table-mounted device that utilizes video images of a
person’s eyes and reflections in the eyes of near-infrared reference lights. The device does
not require any head-mounted equipment and does not interfere with the EEG/ERP data
collection.
8. Educational Neuroscience at Vanderbilt University
Vanderbilt University (Session 2: 12:45-1:45 p.m.) Author: Educational Neuroscience Initiative Consortium
Educational neuroscience is the application of neurobiological processes to areas of
educational importance including child development, educational assessment, reading/math
instruction, and psychosocial functioning. Educational neuroscience allows the placing of
important educational issues within a scientific context that compliments the social science
basis of educational research and the biological basis of learning and behavior in
neuroscience. From these collaborative questions a better understanding of how the brain is
involved in learning, as well as more effective ways of teaching, should emerge. Although a
scientific understanding of how the brain is changed by educational interventions is only
emerging, it is likely to help contribute to the future of teacher education and the
development of educational policies in the 21st century.
Contacts:
Craig Kennedy, Ph.D.
Laurie Cutting, Ph.D.
Bruce McCandliss, Ph.D.
Mark Wallace, Ph.D.
9. Support Services for Community Engaged Research:
Community Engaged Research Core
Vanderbilt University (Session 1: 11:45 a.m.-12:45 p.m.) Presenter: Yvonne Joosten Author: Yvonne Joosten Part of the Vanderbilt Institute for Clinical and Translational Research (VICTR), the
Community Engaged Research Core (CERC) offers support services and activities that bring
community and academic partners together to design, implement, evaluate, and disseminate
health-related research studies that enhance the capacity of all participants to address health
priorities among diverse communities. CERC currently offers an evolving set of services that
bring researchers and community organizations together, help partners define and refine
research questions and research designs, support initial steps in the exploration of these
questions, and enable dissemination of findings that will impact practice and policy, reduce
disparities, and improve the health of Tennessee communities.
10. Statistics and Methodology: Help is Available for VKC
Members and Associates
Vanderbilt Kennedy Center Core (Session 2: 12:45-1:45 p.m.) Presenter: Warren Lambert, Ph.D. Authors: Mary Dietrich, Ph.D., Frank Harrell, Ph.D., Warren Lambert, Ph.D., Xu Lei,
Chun Li, Ph.D., Jon Tapp, Julie Lounds Taylor, Ph.D., Andrew Tomarken, Ph.D., Lily
Wang, Ph.D.
This poster introduces the free services available from the VKC Statistics and
Methodological Core (Core C) and the Department of Biostatistics. The goal of this poster is
to reach VKC members who are unaware of the free consultation services they could be
receiving as VKC members, investigators, or associates.
At the poster session, attendees can meet consultants and ask questions about free support
available from VUMC Biostatistics Clinics (Harrell), Behavioral statistics (Lambert),
Observational Methods and software developed at VKC (Tapp), and Biostatistics and
Genetics (Wang).
11. Parent Sleep Education in Autism: Effect of a Standardized
Pamphlet on Sleep Latency
Vanderbilt Kennedy Center Core (Session 1: 11:45 a.m.-12:45 p.m.) Presenter: Karen Adkins Authors: Karen Adkins, Suzanne Goldman, Ph.D., Deborah Wofford, Diane Fawkes,
Beth Malow, M.D.
Background: Sleep difficulties are common reasons why parents seek medical intervention
in children with autism spectrum disorders (ASD).
Objectives: To determine the efficacy of a sleep education pamphlet on sleep latency (time
to fall asleep) in children with ASD.
Methods: Children were ages 2- 10 years, enrolled in the Autism Treatment Network at
Vanderbilt University and Cincinnati sites, with a clinical diagnosis of ASD, confirmed by the
Autism Diagnostic Observation Schedule. Parents were randomly assigned to receive a sleep
education pamphlet containing information about daytime habits, bedtime routine, and
sleep environment. Children wore actigraphy devices, which measure activity and rest to
estimate sleep parameters, prior to receiving the pamphlet (baseline) and two weeks after
randomization (treatment). Sample size of 36 participants was predetermined to detect a
difference in sleep latency of at least 30 minutes in children whose parents received the
pamphlet. Independent t-tests were performed to compare mean sleep parameters at
baseline, and mean change in sleep parameters by treatment.
Results: As shown in the Table, the group receiving the pamphlet showed improvement
from baseline in all sleep parameters, although statistical significance was not reached (p >
0.10). Differences observed between treatment and control groups on mean change in sleep
parameters showed significance (p = 0.04) only for sleep efficiency in the pamphlet group;
this was not clinically significant.
Sleep Education Program‐ Treatment Results in Children with ASD No Pamphlet (n = Pamphlet (n = 17) 19) Baseline (mean, Treatment (mean, Baseline (mean, Treatment (mean, SD) SD) SD) SD) Age, years 5.4 (2.4) 7.1 (2.5) Sleep Latency, min 56.7 (27.1) 49.5 (26.7) 52.1 (25.1) 61.3 (47) Sleep Efficiency, % 75.5 (6.1) 77.8 (7.0) 76.8 (6.0) 75.1 (6.7) Wake Time after Sleep 61.9 (27.4) 60.4 (32.1) 53.2 (20.2) 59.9 (24.2) Onset, min Total Sleep Time, min 465.7 (66.3) 483.0 (67.8) 461.4 (42.4) 470.8 (35.3) Fragmentation, min 36.8 (9.0) 36.3 (10.9) 32.2 (7.2) 33.3 (7.5) Conclusions: Providing a sleep education pamphlet to parents of children with ASD did
not significantly improve sleep latency. We are conducting studies to determine if more
intensive education improves sleep patterns in this population.
Support: Health Resources and Services Administration (UA3 MC11054)
12. The Influence of Spatial Receptive Field Architecture on
the Temporal Dynamics of Multisensory Interactions in the
Superior Colliculus
Systems Neuroscience (Session 2: 12:45-1:45 p.m.) Presenter: Dipanwita Ghose, Graduate Student Authors: Dipanwita Ghose, Matthew Fister, Mark Wallace, Ph.D.
Lab P.I. or Faculty Mentor: Mark Wallace, Ph.D.
Department or Program: Psychology
Spatial and temporal proximity and stimulus effectiveness play a major role in shaping
multisensory interactions. Emerging evidence suggests a strong interdependency between
these factors such that they cannot be considered in isolation. Here we continued this
analysis by focusing on how changes in stimulus location affect the temporal dynamics of
both unisensory and multisensory responses in cat superior colliculus (SC) neurons.
Confirming prior work, the initial analyses revealed a striking heterogeneity to the structure
of the unisensory (i.e., visual and auditory) and multisensory spatial receptive fields (SRFs)
of SC neurons, with dramatic differences in response magnitude being seen for stimuli
positioned at different SRF locations. In addition, it was demonstrated that the SC
multisensory neurons exhibited single as well as multiple excitatory regions within the
spatial receptive field architecture. This complex SRF architecture may support the role of
SC in motion processing in a way that will be expanded upon. Extending this analysis
further, these magnitude differences were accompanied by complex changes in temporal
response dynamics, with spatially-dependent changes being seen in response latency,
duration, peak firing times and rates, etc., resulting in the creation of spatiotemporal
receptive field (STRF) representations. The STRF structure differed for each of the
modalities and for the multisensory combination, and most importantly created a predictive
framework for examining multisensory interactions in which response efficacy appeared to
play a foundational role. Together, these data reveal a heterogeneity and complexity to SC
STRF structure whose functional role is speculated upon.
Keywords: , multisensory, superior colliculus, spatiotemporal dynamics, receptive field, integration
13. Oxysterols Formed from the Most Oxidizable Lipid
7-Dehydrocholesterol in vitro and in vivo Implications for
Smith-Lemli-Opitz Syndrome
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.) Presenter: Libin Xu, Ph.D., Assistant Professor Authors: Libin Xu, Ph.D., Zeljka Korade, Ph.D., Connor Lamberson, Richard
Shelton, M.D., Ned Porter, Ph.D. Lab P.I. or Faculty Mentor: Zeljka Korade, Ph.D., Richard Shelton, M.D., Ned Porter,
Ph.D.
Department or Program: Chemistry and Psychiatry
Smith-Lemli-Opitz syndrome (SLOS) is a devastating metabolic and developmental disorder
that is characterized by multiple congenital malformation and mental retardation. 7Dehydrocholesterol (7-DHC) is accumulated in SLOS patients due to mutations in the gene
encoding 7-DHC reductase (Dhcr7), the enzyme that reduces 7-DHC to cholesterol. In our
studies on the reactivity of lipids toward free radical-mediated peroxidation reactions, 7DHC was found to be the most oxidizable lipid ever known. Over a dozen 7-DHC-derived
novel oxysterols were discovered in peroxidation reactions in solution. More significantly,
multiple new oxysterols were identified in Dhcr7-deficient Neuro2a cells, SLOS human
fibroblasts, and Dhcr7-KO mouse brain by HPLC-MS, while they are not present in the
controls. The 7-DHC-derived oxysterols were found to reduce cell viability in a dose- and
time-dependent manner at sub-M to M concentrations. The 7-DHC oxysterol mixture
added to control Neuro2a cells also triggers the gene expression changes that were
previously identified in Dhcr7-deficient Neuro2a cells. In some preliminary tests,
antioxidants were found to suppress the formation of the oxysterols in SLOS cell models.
Thus, we propose that the 7-DHC-derived oxysterols may play important roles in the
pathogenesis of SLOS and antioxidant supplementation may be an effective therapeutic
approach toward SLOS.
Keywords: Smith-Lemli-Opitz syndrome, 7-dehydrocholesterol oxidation, oxysterol, gene expression,
antioxidant
14. SENSE Theatre Intervention Research Program for
Children with Autism
Clinical and Behavioral Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Blythe Corbett, Ph.D., Assistant Professor Authors: Blythe Corbett, Ph.D., Laura Constantine, Clayton Schupp, Ph.D., Tori
Stromp, Ritu Sharma
Lab P.I. or Faculty Mentor: Blythe Corbett, Ph.D.
Department or Program: Psychiatry
Background: Autism is defined by impairment in social interaction, reciprocal
communication and flexible adaptation to the changing environment. Actors excel in many
of these very skills that children with autism spectrum disorder (ASD) often lack; therefore,
they may serve as master models for intervention.
The purpose of these studies was to evaluate social stress and adaptive functioning in ASD
before and after a novel, community-based theatre intervention called “SENSE (Social
Emotional NeuroScience) Theatre” designed to improve social and emotional functioning.
The intervention included peer and video modeling, behavior therapy techniques, social
reinforcement and theatrical techniques, which were embedded in a full musical theatrical
production. We hypothesized that participation in the program would result in reduced
stress response as measured by cortisol. In a second study with different participants, we
examined parental report the participant’s adaptive behavior and anxiety before and after
the SENSE Theatre intervention.
Methods: In the first study eight children with ASD were paired with typically developing
peers that served as expert models. Neuropsychological and biological measures were
assessed in a pretest-posttest design using paired sample t-tests. Stress responsivity was
measured using a repeated measures approach by obtaining salivary samples at the
beginning and end of the practice for the First, Middle, and Last Rehearsal.
Results: Cortisol level showed a significant interaction between Intervention Time (First,
Middle, and Last rehearsals) and Rehearsal Time (Pre and Post Rehearsal) F(1,6)=19.302,
P=0.001. There were also main effects for Time F(1,6)=16.81 P<0.0001 and for Pre-Post
Rehearsal, F(1,6)=127.36, P<0.0001. In the second study that included 15 participants with
ASD, parental report of the child’s behavior indicated significant improvement in aspects of
adaptive functioning following the intervention (all p<0.05).
Conclusions: Findings suggest that in addition to demonstrating improvement in social
perception skills, the children with ASD exhibited reduced stress responsivity ostensibly in
response to the peer-supported, theatrical intervention. In addition, parental report
indicated improvement in aspects of adaptive functioning. The current findings suggest that
interventions that include supportive, social interaction alongside behavioral methods may
lead to reductions in heightened stress responsivity as well as improvement in other
important aspects of social and adaptive functioning.
Keywords: autism spectrum disorders, social interaction, theatre, cortisol, peer
15. Developmental Differences between Exact and
Approximate Subtraction
Clinical and Behavioral Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.) Presenter: Liane Moneta, Graduate Student Authors: Liane Moneta, Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
Exact and approximate numerical processing engage different brain networks in adults, with
exact number processing showing increased recruitment of the angular gyrus and
approximate number processing showing increased recruitment of the intraparietal sulcus.
To examine the development of these systems we created a non-symbolic subtraction
paradigm to directly contrast these two systems in early elementary school children (grades
K-3). Children viewed videos of a woman removing a small set of discs (1-7) from a bucket
and selected which of three disc pictures (1, 2 or 3) showed how many discs remained in the
bucket. By varying the exposure time of the numerosities, this paradigm isolates exact vs.
approximate arithmetic processing. In the exact subtraction version, children had ample
time to identify both operands in the subtraction problems. In the approximate version
children viewed the operands for 125ms. Performance degraded systematically with set size,
yet in different ways across the duration manipulation. For approximate subtraction, all
grades showed the same effect of set size and similar error patterns. In contrast, exact
subtraction set size effects changed dramatically across grade levels, with strongest effects
occurring in kindergarten age children. Additionally, exact subtraction error distribution
(ratio of one-away errors to two-away errors) showed a sharpening of acceptable responses
with grade level, potentially reflecting progressive sharpening of ‘number neuron’ tuning
curves. This paradigm provides cognitive metrics separating exact and approximate
processes critical to studying development of these brain systems in fMRI.
Keywords: mathematics
16. Grey Matter Volume Differences in Limbic and Prefrontal
Cortical Areas Characterize Inhibited Temperament
Systems Neuroscience (Session 2: 12:45-1:45 p.m.) Presenter: Jacqueline Clauss, Graduate Student Authors: Jacqueline Clauss, Jennifer Blackford, Ph.D.
Lab P.I. or Faculty Mentor: Jennifer Blackford, Ph.D.
Department or Program: Psychiatry
Background: Inhibited temperament is the predisposition to respond to new people,
places, or things with avoidance and is associated with an increased risk of developing social
phobia. People with an inhibited temperament have an increased amygdala response to
novel and fear faces, and a reduced prefrontal cortex response to fear faces. Preliminary
studies suggest that inhibited temperament is associated with volume differences in the
amygdala, hippocampus, and orbitofrontal cortex (OFC). While cortical thickness has been
assessed, no study has examined whole brain grey matter volumes in inhibited
temperament.
Methods: We compared grey matter volume between subjects with an inhibited (n = 45)
and uninhibited temperament (n = 46). To assess grey matter volume, we used voxel based
morphometry in SPM8 and the DARTEL toolbox. We examined the following a priori
regions of interest: amygdala, hippocampus, parahippocampal gyrus, anterior cingulate
cortex (ACC), dorsolateral prefrontal cortex (dlPFC), insula, and OFC. A cluster-based
threshold was used for a corrected p < .05 for each ROI. We also performed a whole brain
analysis. Within the inhibited temperament group, we compared those with and without
current social phobia. All analyses were performed with the following covariates: race,
gender, age, intracranial volume, and handedness.
Results: Subjects with an inhibited temperament had a significantly increased volume in
the left posterior hippocampus, left parahippocampal gyrus, right lateral dlPFC, left caudate,
and a trend in the left amygdala (p = .06). Decreased volumes in inhibited temperament
were found in a more anteromedial region of the left posterior hippocampus, bilateral insula,
bilateral medial dlPFC, and right OFC. Within inhibited temperament, social phobia was
associated with decreased volumes of the bilateral ventral ACC, hippocampus, OFC, and
dlPFC. Subjects with social phobia had an increased volume in right posterolateral dlPFC.
Conclusions: Increased volume of the amygdala and hippocampus may be the structural
basis of the increased response to novelty and avoidance behavior in inhibited temperament.
Reduced volume of prefrontal cortical regions is likely the neural basis for reduced cognitive
control over emotional responses in inhibited temperament, as well as for increased anxiety
in inhibited subjects with social phobia.
Keywords: temperament, amygdala, hippocampus, prefrontal cortex, voxel-based morphometry
17. Neural Precursor Induction from Human Induced
Pluripotent Stem Cells Using Small Molecules
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.) Presenter: Michael Litt, Undergraduate Student Authors: Michael Litt, Diana Neely, Ph.D., Andrew Tidball, Asad Aboud, M.D.,
Bingying Han, Kevin Ess, Ph.D., M.D., Charles Hong, Aaron Bowman, Ph.D.
Lab P.I. or Faculty Mentor: Diana Neely, Ph.D., Kevin Ess, Ph.D., M.D., Aaron
Bowman, Ph.D.
Department or Program: Neurology
The recent discovery of induced pluripotent stem cells (iPSC) has sparked wide-ranging
investigations into various neurological disease hypotheses previously approachable only
though animal models. The development of stem cell models for neurodegenerative diseases
must first overcome the rather formidable task of creating cheap and efficient differentiation
protocols to produce the regio-specific neurons affected in such diseases. The regulation of
the TGF- family of proteins has been shown to play essential roles during iPSC
maintenance and differentiation. Coordinately, dual inhibition of the BMP and TGF-
pathways through the use of noggin, and the small molecule SB-431542, respectively, has
been shown to induce neural precursor cell formation. Our study compares the efficacy of
noggin and DMH1, a small molecule that inhibits the BMP pathway similar to noggin, to
induce neural precursor induction. To determine neural precursor conversion efficiency, we
quantified the expression of the neural precursor markers PAX6 and SOX1 and the iPSC
markers Nanog and OCT4 by immunocytochemistry and qPCR. We assessed the neural
induction of stem cell lines of two brothers with a compound heterozygous PARK2 mutation,
of a patient with a genetic mutation in the mTOR signaling pathway, and a control patient.
By using DMH1 as a small molecule replacement for noggin, this study shows that the
combined inhibition of TGF-, and BMP-signaling pathways can be performed without the
use of expensive and highly variable recombinant proteins.
Keywords: hIPSC, neuralization, small molecules, stem cells, immunocytochemistry
18. A Novel 7-Dehydrocholesterol-Derived Oxysterol Observed
in Cells and Tissues from Different SLOS Models
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.) Presenter: Zeljka Korade, Ph.D., Assistant Professor Authors: Zeljka Korade, Ph.D., Libin Xu, Ph.D., Ned Porter, Ph.D.
Lab P.I. or Faculty Mentor: Zeljka Korade, Ph.D., Ned Porter, Ph.D.
Department or Program: Psychiatry
Reduced or absent enzymatic activity of 7-dehydrocholesterol reductase (Dhcr7) leads to
Smith-Lemli-Opitz Syndrome (SLOS), which is characterized by multiple congenital
malformations, incomplete myelination, mental retardation, and autism-like symptoms. In
SLOS, the tissue cholesterol and total sterol levels are markedly reduced while the
concentration of 7-dehydrocholesterol (7-DHC) is greatly elevated. Based on our discovery
that 7-DHC is highly prone to auto-oxidation producing a mixture of oxysterols in vitro, we
screened specific cells and tissues from different SLOS models for the presence of 7-DHC
derived oxysterols. We identified a novel oxysterol, 3β,5α-dihydroxycholest-7-en-6-ne
(DHCEO). It is present in the human fibroblasts derived from SLOS patients, in Dhcr7deficient Neuro2a cells, and in the mouse Dhcr7-KO brain samples. While the concentration
of DHCEO differs among specific brain regions and different cell populations, its level
depends on the level of 7-DHC. Since DHCEO accumulates in the mouse brain we are testing
the cellular effect of DHCEO in neuronal and glial cultures and looking for changes in
cellular survival, morphology, and gene expression.
Keywords: cholesterol, 7-dehydrocholesterol, oxysterol, Smith-Lemli-Opitz syndrome
19. Peer Social Interaction and Cortisol Responsivity in
Children with Autism
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Blythe Corbett, Ph.D., Assistant Professor Authors: Blythe Corbett, Ph.D., Clayton Schupp, Ph.D., Ritu Sharma, Tori Stromp
Lab P.I. or Faculty Mentor: Blythe Corbett, Ph.D.
Department or Program: Psychiatry
Background: Play is critical for the development of social, cognitive, and motor skills.
Even though poor reciprocal social interaction is the hallmark deficit in autism, surprisingly
few ecologically valid observational studies of play exist. The study was designed to examine
stress responsivity as measured by cortisol comparing children with autism to neurotypical
peers during an ecologically valid playground paradigm. In contrast to many studies of
physiological responsivity, which aim to solicit a stress response, the paradigm was designed
to emulate a “real life” environment of play to determine whether such environments would
be physiologically stressful.
Participants: Included 45 boys 8-12 years (21 with autism). The experimental group
consisted of children diagnosed with Autistic Disorder (APA, 2000) and corroborated by the
(ADOS-G; (Lord et al., 1999).
Results: Repeated measures analysis of cortisol revealed a model that included time of
measurement, diagnosis (autism vs. typical), age (median older vs. younger), and a
diagnosis+age interaction term. A significant model was revealed (χ²(4)=22.76, P<0.0005)
that included time of measurement, diagnosis, and age as main effects and an interaction
between diagnosis and age. Thus, older children with autism exhibited enhanced cortisol
responsivity compared to their average afternoon cortisol levels, baseline and compared to
younger peers.
Discussion: Our ecologically valid paradigm, designed to emulate naturally occurring
social interactions, resulted in a significant stress response in many of the children with
autism. Furthermore, distinct patterns emerged within the autism group based on
developmental (older), biological (cortisol responder) and behavioral patterns (engaged in
group social interaction). Since the enhanced cortisol response was observed in children
who engaged in peripheral play, it does not support the notion of a response to social threat.
Rather, the responsivity appears to reflect attendant metabolic preparedness and enhanced
arousal from engaging socially likely as a result of poor social competence and coping
strategies. The data suggest that many children with autism activate hypothalamicpituitary-adrenal responses in non-threatening social situations, which appears to be a
function of age and level of social engagement. The findings support the need to teach
coping strategies in addition to fundamental social skills to youth with autism.
Keywords: autism spectrum disorders, social interaction, stress, cortisol, play
20. Frontal vs. Parietal Contributions to Elementary School
Children’s Number Concepts
Systems Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Edward Hubbard, Ph.D., Postdoctoral Fellow Authors: Edward Hubbard, Ph.D., Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
During early elementary schooling (K-3), children’s number concepts undergo radical
changes, especially in the small number range (5-9, the “counting range”) where children
can perform exact calculations. One of these critical conceptual changes is an increased
understanding of the larger/smaller relations between numbers. While parietal regions are
sensitive to differences in non-symbolic quantity in 4-month-old infants, symbolic
processing of quantities in this range depends on frontal circuitry more in children than in
adults. To examine frontal and parietal contributions to symbolic and non-symbolic quantity
processing in the counting range, we modified an fMRI-adaptation paradigm that has
previously demonstrated quantity sensitivity in children and adults. Arrays of dots of a
standard quantity (6 or 8) were presented repeatedly, alternated with rare deviants that
were either numerically close to or far from (5 or 9) the standard, in either the same format
(dots) or a different format (digits). Children and adults showed larger responses to far
deviants than to close deviants (context-dependent dishabituation), but these responses
included frontal regions in children that were not activated in adults. Additionally, responses
to symbolic quantity differed: For adults, we observed context-dependent dishabituation for
both dots and digits, while for children context-dependent dishabituation was reliably
observed for dots, but was less reliable for digits. These results suggest that understanding
numerical relations and explicit representations of the links between quantities and symbols
are initially effortful processes, mediated by prefrontal cortex, with increasing practice and
automaticity leading to increased specialization of parietal brain regions.
Keywords: numerical cognition, parietal cortex, frontal cortex, fMRI
21. Differential Response to Chronic Unpredictable Stress in
Integrin 3 Heterozygous Mice
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Seth Varney, Undergraduate Student Authors: Seth Varney, Tammy Jessen, Ana Carneiro, Ph.D.
Lab P.I. or Faculty Mentor: Ana Carneiro, Ph.D.
Department or Program: Pharmacology
Dysfunctional information processing has been implicated in many debilitating mood
disorders, including major depressive disorder. The integrin v3, a molecule involved in
cell adhesion, has been shown to associate with and modulate the activity of the serotonin
transporter (SERT). As serotonergic dysfunction is also observed in many patients with
these disorders, the interaction between SERT and integrin v3 may represent a novel
mechanism in the regulation of mood. Chronic stress is often a significant factor in the
etiology of mood disorders such as major depressive disorder, and elucidating the role of the
integrin 3 in the response to chronic stress may help to develop more effective treatments
for these disorders. Male mice heterozygous for the Itgb3 gene were used to elucidate its
role in the behavioral response to chronic stress. A chronic unpredictable stress paradigm
was used in which mice were housed either individually or in groups, and daily mild
stressors applied for six weeks to the singly housed individuals. Nest building behavior was
measured weekly to evaluate anxiety-related behavior. Mice heterozygous for the Itgb3 gene
were demonstrated to exhibit significant differences in shredding behavior prior to the
implementation of the chronic stress paradigm. Following the six week chronic stress
treatment, anxiety and depressive related behaviors were evaluated using the elevated zero
maze, open field test, forced swim test, and tail suspension test. Preliminary analysis of
these results suggests that the Itgb3+/- mice are more resilient to chronic stress, although
further analysis needs to be done to confirm this finding. Following behavioral testing, mice
were sacrificed and hippocampal, neocortical, and midbrain tissue samples were collected
for biochemical and neurochemical analysis. We predict that heterozygosity of the Itgb3
gene will result in increased resilience to chronic stress. Understanding the modulatory
networks involved in mood regulation can aid in the development of treatments for the
disorders that arise as a result of their dysfunction. Mood disorders resulting from an
inability to cope with chronic stress may be the result of the failure of one of these
modulatory networks. The SERT/v3 interaction may represent one of these modulatory
processes, and our work aims at understanding its relevance in the regulation of mood.
Keywords: stress, integrin, serotonin transporter
22. Phonological Awareness Training with Children with
Hearing Loss
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Krystal Werfel, Graduate Student Authors: Krystal Werfel, Melanie Schuele, Ph.D.
Lab P.I. or Faculty Mentor: Melanie Schuele, Ph.D.
Department or Program: Hearing and Speech Sciences
Purpose: Some children with hearing loss have great difficulty in acquiring early language
and literacy skills. Despite technological advances in amplification for children with hearing
loss (e.g., cochlear implants), the average reading level for this population has not increased
in the past several decades. Phonological processing deficits in children with hearing loss
may contribute to poor reading outcomes. The purpose of this single subject study was to
evaluate whether initial sound segmentation training increased initial sound segmentation
ability in preschool children with hearing loss.
Method: Two preschool children with hearing loss participated in this multiple probe
design single subject study. The children participated in individual intervention that taught
initial sound segmentation (37-39 half-hour sessions). Assessment of children’s initial sound
segmentation skill occurred at the beginning of each session.
Results: Results indicated that initial sound segmentation training increased children’s
performance on the initial sound segmentation assessment measures in the children with
hearing loss. The children exhibited some maintenance of skill when training ceased, but
maintenance was not complete. Generalization to sounds not taught was generally not
observed. Error analysis gave insight to children’s skill.
Conclusions: Phonological awareness training was associated with an increase in
phonological awareness skill for these two children with hearing loss. Future research
should explore the effectiveness of phonological awareness training for all children with
hearing loss. In addition, future research should explore the effects of phonological
awareness training on literacy outcomes for children with hearing loss.
Keywords: phonological awareness, hearing loss, early literacy, intervention
23. Using Peer Models in the Context of Small-Group Direct
Instruction to Teach Social Skills to Young Children with
Autism
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Jennifer Ledford, Graduate Student Authors: Jennifer Ledford
Lab P.I. or Faculty Mentor: Mark Wolery, Ph.D.
Department or Program: Special Education
This study evaluated whether children with disabilities acquire appropriate social behaviors
via observational learning when peers modeled these skills during small group direct
instruction. A multiple probe across behaviors design was used, and was replicated across
participants. Three preschoolers with disabilities (one with Down’s syndrome and two with
autism spectrum disorders) were taught to name stimuli, using progressive time delay, in a
small group with two typically-developing peers. Prior to the group sessions, peers were
taught to share rewards given for correct responding and to say “thank you” when a peer
shared. Results from Participant 1 showed the participant (a) acquired targeted academic
behaviors (Figure 1), (b) began sharing and saying thank you during instructional sessions
(Figure 2), and (c) generalized social skills to generalization settings designed to resemble
classroom activities (Figure 2). Two additional participants with autism spectrum disorders
have completed the first and second tiers of instruction, respectively. Their data suggest
children with autism may also acquire and generalize peer-modeled social and academic
skills during small group instruction (Figures 2, 3, 4, and 5). Together, these results suggest
small group direct instruction is an effective context for using peer modeling of social skills
to increase appropriate social behavior.
Keywords: small group instruction, social interaction, autism spectrum disorders, Down syndrome
24. Functional Implications of GAD67 Downregulation in a
Subpopulation of Interneurons
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Martin Schmidt, Graduate Student Authors: Martin Schmidt, Krassimira Garbett, Ph.D., Szatmar Horvath, M.D., Ph.D.,
Karoly Mirnics, M.D.
Lab P.I. or Faculty Mentor: Karoly Mirnics, M.D.
Department or Program: Psychiatry
GAD67 is a CNS-specific enzyme that produces GABA, the main inhibitory neurotransmitter
in the brain. GABAergic interneuron subtypes can be classified by their molecular contents
(neuropeptides/calcium-binding proteins) and have distinct physiological and
morphological characteristics that contribute to differential regulation of pyramidal cell
output. GAD67 downregulation is one of the most robust and reproduced findings in postmortem tissue from schizophrenic patients across many brain regions. Mounting evidence
suggests that certain interneuron subtypes may be more GAD67-deficient than others.
Furthermore, it is not clear whether this deficit is caused by the disease process or is a cause
of the disease process. To determine empirically whether GAD67 downregulation is
sufficient to induce alterations in the brain and behavior and whether these alterations are
dependent on the interneuron subtype(s) affected, we have developed a novel method for
silencing GAD67 in distinct subpopulations of interneurons in a mouse model. Our initial
efforts have focused on interneurons containing neuropeptide Y (NPY+). We present here
our initial characterization of NPYBAC transgenic mice highlighting their molecular and
behavioral phenotypic profile which includes dopamine system dysregulation, hyperactivity,
and memory impairment. Interestingly, the profile of these mice is strikingly similar to
other mouse models of schizophrenia susceptibility genes and, taken together, may provide
evidence of disparate genetic mechanisms converging into a final common molecular and
behavioral pathway.
Keywords: schizophrenia, animal models, interneurons, gene expression, behavior
25. Student Computers: Six-Year-Olds Believe That Computers
Can Learn
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Maria Vazquez, Graduate Student Authors: Maria Vazquez, Megan Saylor, Ph.D., Daniel Levin
Lab P.I. or Faculty Mentor: Megan Saylor, Ph.D.
Department or Program: Psychology and Human Development
The benefits of peer tutoring are well known (e.g. Bargh & Schul, 1980) and, as computers
become more common in schools, some researchers have begun to investigate the use of
computers as stand-ins for peers. For example, 5th graders have been shown to benefit from
teaching computers about science topics (Wagster et al., 2007). As this practice becomes
more common it may be used as an instructional tool for younger children. However, in
order for a child to effectively engage in a “peer” tutoring session with an artificial agent, two
conditions must be met. A child must believe that the agent can learn and they must be able
to monitor the agent’s knowledge states throughout the tutoring session. These tasks may be
more difficult for younger children interacting with a computer. Therefore, a young child
who would benefit from tutoring a human peer may not benefit equally from tutoring a
computer agent. To investigate young children’s understanding of the abilities of computers,
6-year-olds were offered the opportunity to teach a computer and person how to build a set
of simple structures. An experimenter first showed children how to build a structure out of
Lego blocks and then let children demonstrate the building for each agent. When children
returned after demonstrating to each agent, the researcher found a “mistake” in her initial
build. She showed children the correct way to build the structure and asked children to fix
the error for only one of the agents. Children overwhelmingly chose to correct the error for
the computer agent. This finding indicates that young children believe that a computer can
learn and suggests that children may be able to monitor the knowledge states of artificial
agents.
Keywords: knowledge state attribution, learning by teaching, computers
26. Abnormal Cortical Activation During Action Imitation in
Schizophrenia
Systems Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Katharine Thakkar, Graduate Student
Authors: Katharine Thakkar, Joel Peterman, Heathman Nichols, Natasha Matthews,
Sohee Park, Ph.D.
Lab P.I. or Faculty Mentor: Sohee Park, Ph.D.
Department or Program: Psychology
Objective: Social impairments are cardinal features of schizophrenia. Imitative processes
play a large role in social behavior, and deficits in basic imitation ability have been reported
in schizophrenia. The goal of this study was to investigate differences in neural activity
associated with finger movement imitation between patients and controls. Specifically, we
were interested in activity in inferior frontal gyrus (IFG), superior temporal sulcus/gyrus
(STS/STG), and inferior parietal cortex (IPC), as these areas are key nodes in the imitation
network.
Methods: Schizophrenia patients and healthy controls underwent fMRI while either
executing or observing imitative or non-imitative actions. Results were examined at an
uncorrected p-value of 0.005.
Results: In controls, activity was greater when executing imitative versus non-imitative
actions in bilateral IFG and STS/STG. Schizophrenia patients did not show significantly
greater activity when executing imitative versus non-imitative actions in any of our regions
of interest. Direct group comparison revealed greater activity for controls than patients
when executing imitative versus non-imitative actions in right IFG and STS.
Conclusions: This study provides preliminary evidence for abnormal activity in neural
regions subserving imitation in schizophrenia. These data provide a first step towards a
more psychologically and biologically constrained framework for understanding social
deficits in schizophrenia.
Keywords: schizophrenia, imitation, social cognition, fMRI, mirror neurons
27. Characterization of Induced Pluripotent Stem Cell Lines
from Patients with Tuberous Sclerosis Complex
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Mark Goodman, Undergraduate Student
Authors: Mark Goodman, Bryan Cawthon, Andrew Tidball, Diana Neely, Ph.D.,
Aaron Bowman, Ph.D., Kevin Ess, Ph.D., M.D.
Lab P.I. or Faculty Mentor: Diana Neely, Ph.D., Aaron Bowman, Ph.D., Kevin Ess,
Ph.D., M.D.
Department or Program: Neurology
Tuberous Sclerosis Complex (TSC) is a genetic disorder that features the growth of benign
tumors in the brain, known as tubers, and on other vital organ systems such as the heart,
kidneys, lungs and skin. TSC is known to be caused by a mutation at one or both of two
genetic loci, TSC1 and TSC2, on chromosome 9 and 16, respectively. TSC1 and TSC2 function
as a complex to regulate the mammalian target of rapamycin (mTOR) signaling pathway,
which promotes cell growth and proliferation. A mutation of TSC1 or TSC2 leads to
disinhibition of the mTOR kinase pathway, leading to growth of tumors. Although a cure for
TSC has not been found, recent research has shown that rapamycin, a potent mTOR
inhibitor, causes a decrease in cell-proliferation in TSC patients and may also reverse many
of the clinical features.
In order to understand this interaction as well as describe the molecular basis of TSC for
future treatments, induced pluripotent stem cells (iPSCs) were developed from fibroblasts of
a skin growth (“Shagreen patch”) of a patient with TSC. The ultimate goal, in turn, was to
direct these cells towards a neural fate for future study. Intriguingly, one of these iPSC lines,
known as STS Shag B1, appears to rapidly proliferate and spontaneously generate neural
appearing cells, even in stem cell maintenance media. In addition, stark differences are
noticed between the controls and Shag B1cells in neurite polarity and process length. As we
hypothesized these deficits were due to hyperactive mTOR signaling, rapamycin was added
to both Shag B1cells and control iPSCs. Overall, we found the phenotype of promiscuous
neutralization was reversible with rapamycin giving further validation to the use of this drug
as a rational treatment for patients with TSC. Further studies will address mechanisms
causing STS Shag B1 properties unusual deficits, and will hopefully lead to a greater
knowledge of TSC and future treatments.
Keywords: iPSC, Tuberous Sclerosis, rapamycin, mTOR, characterization
28. Vasodilator-Stimulated Phosphoprotein VASP Induces
Actin Assembly in Dendritic Spines to Promote Their
Development and Potentiate Synaptic Strength
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Wan-Hsin Lin, Graduate Student
Authors: Wan-Hsin Lin, Caroline Nebhan, Bridget Anderson, Donna Webb, Ph.D.
Lab P.I. or Faculty Mentor: Donna Webb, Ph.D.
Department or Program: Biological Sciences
Dendritic spines are small actin-rich protrusions that receive the majority of excitatory
synaptic input in the brain. The actin-based dynamics of spines are thought to mediate
synaptic plasticity, which underlies cognitive processes, such as learning and memory.
However, little is known about the molecular mechanisms that regulate actin dynamics in
dendritic spines and synapses. In this study, we show that the multifunctional actin-binding
protein VASP regulates the density, size, and morphology of spines by inducing actin
assembly in these structures. Knockdown of endogenous VASP by siRNA led to a significant
decrease in spine and synaptic density while expression of siRNA-resistant VASP rescued
the defect on spines and synapses. The ability of VASP to modulate spine and synapse
formation, maturation, and spine head enlargement was dependent on its actin-binding
Ena/VASP homology 2 (EVH2) domain and its EVH1 domain, which contributes to VASP
localization to actin-rich structures. Moreover, VASP increased the amount of PSD
scaffolding proteins, including PSD95, Homer, and Shank and the number of surface GluR1containing -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) in
spines. VASP knockdown reduced surface levels of AMPAR, suggesting a role for this
protein in regulating synaptic strength. Consistent with this, VASP significantly enhanced
the retention of GluR1 in spines and increased AMPAR-mediated synaptic transmission.
Indeed, VASP induced a 2.7-fold increase in miniature excitatory postsynaptic current
(mEPSC) frequency and a 1.3-fold increase in mEPSC amplitude compared with
untransfected control neurons. Collectively, our results suggest that actin polymerization
and bundling by VASP are critical for spine formation, expansion, and modulating synaptic
strength.
Keywords: dendritic spines, actin, synaptic transmission, post-synaptic density, AMPA receptors
29. Early Life Experience and the Serotonin System:
A Mechanistic Quest
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Elizabeth Hammock, Ph.D., Instructor
Author: Elizabeth Hammock, Ph.D.
Lab P.I. or Faculty Mentor: Elizabeth Hammock, Ph.D.
Department or Program: Pediatrics
Effective care-giving and early life social support protect individuals from life insults and
risk for depression and anxiety. Effective care-giving likely signals a predictable and
resource-rich environment which could developmentally down-regulate stress and fear
circuitry to preserve future resources. Alternatively, in a resource-poor and unpredictable
environment, less social support during development would increase the probability of
future stress-coping through vigilance and high levels of fear-like behaviors. Developmental
exposure to stress has long lasting consequences on the organization and maintenance of
serotonergic tone in the central nervous system and is associated with increased anxiety-like
traits and risk for major depression. To better understand the neural mechanisms of this
experience-dependent tuning of the serotonergic system, we are implementing a mouse
model of early life stress. In this model, litters of mice are randomly assigned to one of two
conditions: they are weaned at the normal age of 21 post-natal days (P21) or they are weaned
early at 16 post-natal days (P16). After this early life manipulation, both male and female
mice are tested on a battery of anxiety, depression and social behavior tasks. Our pilot data
indicate that as predicted, the P16 group shows a persistent increase in anxiety-like behavior
and altered social behavior. After the behavioral assays are completed, animals are
harvested for brain measures of serotonin system functioning. Our current data suggest that
early weaning in mice is a reliable and robust method to dissect the neural mechanisms of
experience-dependent neurodevelopment.
Keywords: serotonin, animal models, stress, experience-dependent development, anxiety
30. Arousal and Anxiety in Williams Syndrome in Social and
Non-Social Situations: Associations Between Neuroendocrine
Markers and Performance Abilities
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Miriam Lense, Graduate Student
Authors: Miriam Lense, Elisabeth Dykens, Ph.D.
Lab P.I. or Faculty Mentor: Elisabeth Dykens, Ph.D.
Department or Program: Clinical Psychology
Introduction: Williams syndrome (WS) is a genetic neurodevelopmental disorder associated with
hypersociability and high rates of anxiety. In typical populations, hormones released by the
hypothalamic-pituitary-adrenal axis (HPA) relate to levels of arousal and anxiety, particularly in
socially evaluative situations, and also modulate memory consolidation. These hormones are
associated with the hippocampus and amygdala, brain regions known to be aberrant in WS. We
compared HPA activity (via cortisol) in individuals with WS in situations of high social/low cognitive
demands (a musical performance) and low social/high cognitive demands (a cognitive and memory
test battery).
Methods: Thirteen adults with WS provided salivary cortisol samples before and after a solo musical
performance in front of an audience. Individuals were rated for signs of performance anxiety and also
self-rated their own anxiety. Performances were rated for musical ability and parents completed
questionnaires about musical training. An additional six adults with WS (total n=19), as well as
thirteen typically developing (TD) individuals, provided cortisol samples and anxiety ratings before
and after a cognitive battery involving memory for emotional and neutral words and faces.
Results: Cortisol levels in WS measured before and after a musical performance were highly
associated with performance abilities (r’s=.725 and .556, respectively, p’s<.05). No differences
emerged in baseline cortisol levels across the music performance vs. memory battery conditions.
However, while cortisol levels remained constant during musical performances, they significantly
declined in response to the memory battery (Cohen’s d =1.22). Comparing cortisol responses to the
memory battery in WS vs. TD individuals, there was no difference in baseline levels, but the WS group
exhibited a significant cortisol decrease, whereas the TD group exhibited a cortisol increase (Cohen’s
d =.54) (see figure).
Discussion: This study is the first to examine HPA reactivity in WS, and to do so with paradigms
that reflect salient aspects of the WS phenotype. As cortisol levels have routinely been linked to
memory consolidation in TD individuals, these findings suggest important differences in links
between arousal, learning and memory in individuals with WS. Implications are discussed for
learning and memory in WS based on arousal, anxiety, and social versus non-social contexts.
Change in Cortisol Values by
2
Cortisol Change (ng/ml)
1
0
-1
-2
-3
-4
-5
WS PerformanceWS Memory TD Memor
Keywords: Williams syndrome, anxiety, arousal, cortisol, memory
31. Corticostriatallimbic Gray Matter Morphology in
Adolescents Exposed to Childhood Maltreatment
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Kale Edmiston, Graduate Student
Authors: Kale Edmiston, F. Wang, C. Mazure, L. Sinha, H. Blumberg
Department or Program: Neuroscience Graduate Program
Objective: Corticostriatal-limbic gray matter (GM) alterations have been reported in
children and adults exposed to childhood maltreatment (CM). Effects in adolescents are
implicated; however, few studies focus on adolescents. Past studies were performed largely
in psychiatric samples, limiting ability to separate CM effects, and did not assess CM
subtypes or sex. This study examines CM effects in GM in adolescents without psychiatric
diagnoses, and explores CM subtype and sex effects.
Methods: Associations between Childhood Trauma Questionnaire (CTQ) total scores and
regional GM volume were assessed in voxel-based analyses of structural magnetic resonance
scans of 42 adolescents without psychiatric diagnoses. Effects of CTQ subscales (physical,
emotional and sexual abuse; physical and emotional neglect), and sex were explored.
Results: Total CTQ scores correlated negatively with GM volumes in dorsolateral prefrontal
cortex (DLPFC), rostral PFC (RPFC), subgenual PFC (sgPFC), striatum, amygdala, sensory
association cortices and cerebellum. Physical abuse, physical neglect and emotional neglect
showed common RPFC reductions, as well as differing regions of decreases. For physical
abuse these included DLPFC, orbital PFC, insula, and ventral striatum, for physical neglect
the cerebellum, and for emotional neglect DLPFC, orbital PFC, sgPFC, striatum, amygdala,
hippocampus and cerebellum. These latter emotion regulation regions were also associated
with CTQ scores in females; caudate reductions, which may relate to reduced impulse
control, were seen in males.
Conclusions: CM was associated with corticostriatal-limbic GM reductions in adolescents.
These may contribute to vulnerabilities to behavioral difficulties experienced by exposed
adolescents, who may not meet criteria for psychiatric diagnoses. Vulnerabilities may be
moderated by CM type and sex.
Keywords: child abuse/neglect, MRI
32. Minocycline Allieviates Neural Circuit Defects in the
Drosophila Fragile X Model via a Tissue Inhibitor of Matrix
Metalloprotease-Dependent Pathway
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Saul Siller, Undergraduate Student
Authors: Saul Siller, Kendal Broadie, Ph.D.
Lab P.I. or Faculty Mentor: Kendal Broadie, Ph.D.
Department or Program: Biological Sciences, Cell and Developmental Biology
Fragile X Syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1)
product (FMRP), is the most common cause of inherited intellectual disability and autism
spectrum disorders. FXS patients suffer multiple behavioral symptoms, including
hyperactivity and disrupted circadian cycles in addition to learning/memory deficits.
Recently, a mouse FXS model study showed that the tetracycline derivative minocycline may
effectively remediate the disease state via a proposed matrix metalloproteinase (MMP)
inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess
the effects of minocycline treatment on multiple neural circuits and to test this MMP
hypothesis. We first treat Drosophila FMR1 (dfmr1) null animals with minocycline to assay
effects on mutant synaptic architecture in 3 disparate locations: the neuromuscular junction
(NMJ), clock neurons in the circadian activity circuit, and Kenyon Cell neurons in the
Mushroom Body learning/memory center. We find that minocycline strongly restores
normal synaptic structure in all these contexts, suggesting promising therapeutic potential
for FXS treatment. We next test the MMP hypothesis by assaying effects of over-expressing
the sole Drosophila Tissue Inhibitor of MMP (TIMP) on dfmr1 null phenotypes. We find
that TIMP over-expression effectively prevents mutant synaptic architecture defects.
Moreover, removal of Drosophila FMRP (dFMRP) rescues TIMP over-expression
phenotypes, including cellular defects and adult viability. However, of the two Drosophila
MMPs, secreted MMP-1 expression/activity does not appear detectably altered in the dfmr1
null condition. The effect on membrane-anchored MMP-2 is currently unknown due to a
lack of tools. We conclude that minocycline and TIMP over-expression both similarly rectify
neural circuit defects in the Drosophila FXS model, but may be acting through a mechanism
broader than MMP inhibition.
Keywords: autism spectrum disorders, translational regulator, neuromuscular junction, circadian
clock circuit
33. Disrupted Trafficking and Catalytic Modulation of a Novel
ADHD-Associated Dopamine Transporter Coding Variant
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Dhananjay Sakrikar, Graduate Student
Authors: Dhananjay Sakrikar, M. Mazei-Robison, E. Bowton, Aurelio Galli, Ph.D., M.
Gill, Randy Blakely, Ph.D.
Lab P.I. or Faculty Mentor: Randy Blakely, Ph.D.
Department or Program: Neuroscience Graduate Program
The human dopamine (DA) transporter (hDAT) is a presynaptic protein responsible for the
reuptake of DA after vesicular release. Multiple lines of evidence indicate that alterations in
DA signaling contribute to Attention-Deficit Hyperactivity Disorder (ADHD) and its
pharmacotherapy. We have identified multiple, novel, coding variants in a DNA screen of
ADHD subjects, including A559V, that shows anomalous voltage-dependent DA efflux and
response to amphetamine (AMPH). Recently, in an Irish cohort of ADHD subjects, we
identified an additional coding variant hDAT-R615C that is located in a generally wellconserved region of the transporter C-terminus. Prior studies indicate that mutations in the
C-terminus of DAT result in altered interactions of DAT-associated proteins, basal and PKCdependent endocytic defects, and disrupted ER-Golgi export (Torres et al, Neuron, 2001,
Holton et al, Nature Neuroscience, 2005, Fog et al, Neuron, 2006). In both transiently
transfected and stable cells, we observe that the R615C mutation produces a modest
reduction in total and surface DAT protein expression, as well as altered DA transport
kinetics. Although the hDAT-R615C lacks anomalous DA efflux under basal conditions, the
mutant exhibits greatly reduced AMPH-mediated internalization compared to wildtype
hDAT. Functional studies reveal that the hDAT-R615C variant also lacks AMPH-mediated
down-regulation of DA transport. Pre-incubation with the CaMKII inhibitor, KN-93, prior to
AMPH treatments reduced DAT activity in both wildtype and hDAT-R615C. Surprisingly,
cell surface expression of hDAT-R615C did not change upon KN-93/AMPH co-application
whereas the inhibitor attenuated AMPH-mediated surface DAT reduction in wildtype DAT.
These data suggest a heretofore-unrecognized role for CaMKII in DAT catalytic activation
that manifests in the R615C background. Finally, R615C fails to internalize or demonstrate
DA transport down-regulation with PMA treatments. Taken together, these data describe a
prominent alteration of posttranslationally modulated transporter localization and
regulation for the hDAT-R615C coding variant.
Keywords: dopamine transporter, ADHD
34. Benefits of Concreteness Fading for Children with Low
Knowledge of Mathematical Equivalence
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Emily Fyfe, Graduate Student
Authors: Emily Fyfe, Nicole McNeil
Lab P.I. or Faculty Mentor: Bethany Rittle-Johnson, Ph.D.
Department or Program: Psychology and Human Development
A longstanding controversy concerns the use of generalized, abstract symbols versus
perceptually rich, concrete materials to facilitate learning. Although recent evidence suggests
that concrete materials may hinder transfer relative to abstract symbols, many theorists
specifically recommend beginning with concrete materials and fading to the more abstract.
We tested this “fading hypothesis” in the context of children learning mathematical
equivalence. Sixty-three children (M age = 8 years, 5 months) with low knowledge of
mathematical equivalence were given instruction in one of four conditions: (a) concrete only,
(b) abstract only, (c) concrete-to-abstract fading, or (d) abstract-to-concrete fading. Children
in the concrete-to-abstract fading condition performed significantly better than children in
the other conditions on transfer problems designed to assess understanding of mathematical
equivalence. These results suggest that children’s understanding of mathematical concepts
may benefit when problems are presented with concrete materials that are explicitly faded
into more abstract representations.
Keywords: mathematics, concrete manipulatives, learning, symbolic understanding
35. White Matter Structure Underlying Individual Differences
in Children’s Math and Reading Abilities Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Arnaud Viarouge, Ph.D., Postdoctoral Fellow
Authors: Arnaud Viarouge, Ph.D., Suzanne Avery, Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
Microstructural properties of distinct white matter tracts correlate with individual
differences in academic performance in both typically and atypically developing children.
For example, multiple studies demonstrate a consistent association between fractional
anisotropy (FA) in the left Superior Corona Radiata (lSCR) and children’s reading scores
that are distinct from other cognitive abilities such as short term memory (Niogi &
McCandliss, 2006). However, recent investigations linking mathematical abilities to FA in
the lSCR (Van Eimeren et al., 2009, 2010) raise new questions regarding cognitive
specificity. To examine this issue, 3T HARDI DTI scans were collected on 28 typically
developing children (ages 6 to 16) along with standardized behavioural measures of math
and reading skills, and non-verbal IQ. LSCR regions of interest (ROIs) were individually
selected using the Reproducible Objective Quantification Scheme (ROQS).
Results replicated previous findings associating standardized reading scores with FA in this
region, which remained significant after controlling for age and IQ. In contrast, although
scores of mathematical abilities were only marginally associated with FA in this region,
multiple regression analyses demonstrated that math skills accounted for unique variance in
FA after controlling for reading, suggesting that this region plays a role in both reading and
math development.
Keywords: diffusion tensor imaging, numerical cognition, reading
36. Neuronal Oxidative Dysfunction Initiates Temporally and
Spatially Controlled Stress Signaling Through p66Shc
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Jacob Martin, Undergraduate Student
Authors: Jacob Martin, J. Brown, BethAnn McLaughlin, Ph.D.
Lab P.I. or Faculty Mentor: BethAnn McLaughlin, Ph.D.
Department or Program: Neuroscience Graduate Program, Neurology, Neurosurgery
In conditions such as ischemic stroke and perinatal hypoxia-ischemia, blood flow
interruption results in oxygen and glucose deprivation. When coupled with tissue
reperfusion, cells experience a massive increase in oxidative stress. Reactive oxygen species
(ROS) have historically been considered solely as destructive mediators of aging and disease.
Yet others and we have found that precise covalent modifications induced by redox reactions
are emerging as a major category of posttranslational modification acting as an on/off switch
in much the same way as kinases and phosphatases. Redox sensitive kinases are a small
group of such proteins that undergo post-translational modification by oxidation and
reduction resulting in their redistribution, co-association with other proteins, and activation
of signaling cascades. Among these cascades are several recognized for their role as
neuroprotective pathways in the cells of the CNS. The oligomerization of the adapter protein
p66Shc following disulfide formation induced by Cys59 oxidation is a necessary activation
step. The competing, reducing reaction that keeps p66Shc in an inactive state is based upon
activity of the cell’s free radical scavengers. Thus, the sensitivity of p66Shc lies in its ability to
detect when and to what extent oxidative stress surpasses baseline antioxidant capacity. We
address the hypothesis that p66Shc redox regulation directs cell survival via its subcellular
distribution and report that neuroprotection induced through mild mitochondrial stress is
dependent upon ROS-mediated p66Shc activation. Higher levels of ROS, however, can more
aggressively activate p66Shc and induce apoptosis. This newfound, bimodal activity of p66Shc
suggests temporal and spatial regulation of the kinase by redox stress may occur with other
redox sensitive kinases and is an essential mediator of cell fate in response to stress.
Keywords: oxidative stress, neuroprotection, redox signaling, p66Shc, reactive oxygen species
37. Voltage-Gated Ion Channels Are Genetic Modifiers of
Generalized Epilepsy with Febrile Seizures Plus
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Nicole Hawkins, Graduate Student
Authors: Nicole Hawkins, Jennifer Kearney, Andrew Escayg, Melinda Martin, Wayne
Frankel
Lab P.I. or Faculty Mentor: Jennifer Kearney, Ph.D.
Department or Program: Neuroscience Graduate Program
Mutations in the neuronal voltage-gated sodium channel genes SCN1A and SCN2A are
associated with inherited epilepsies, including Generalized Epilepsy with Febrile Seizures
Plus (GEFS+) and Dravet Syndrome (Severe Myoclonic Epilepsy in Infancy). Clinical
severity of these epilepsies vary widely even in people who possess the same mutation. This
variation may be due to the presence of modifier genes. To test the hypothesis that genetic
modifiers can influence monogenic epilepsy, we studied the effect of combining SCN1A,
SCN2A and KCNQ2 mutations using mouse models. Knock-in mice carrying the GEFS+
mutation Scn1aR1648H have decreased thresholds to induced seizures and rare spontaneous
seizures as adults. Scn2aQ54 transgenic mice have a mutation in Scn2a that results in
spontaneous, partial motor seizures in adults. Combining the Scn1aR1648H/+ and Scn2aQ54
mutations in double heterozygous mice results in early-onset, generalized tonic-clonic
seizures and premature death by postnatal day 24 (P24). Electrocorticograph (ECoG)
recordings of Scn1aR1648H/+;Scn2aQ54 double mutants revealed frequent, generalized tonicclonic and partial motor seizures. The voltage-gated potassium channel gene mutation
Kcnq2V182M results in reduced M current which normally controls neuronal excitability by
limiting repetitive firing. Mice carrying the Kcnq2V182M allele exhibit increased susceptibility
to induced seizures, but no spontaneous seizures. Combining the Scn1aR1648H/+ and
Kcnq2V182M/+ mutations in double heterozygous mice results in early-onset, generalized
tonic-clonic seizures and premature lethality, with 42% dying by P25. ECoG monitoring of
Scn1aR1648H/+;Kcnq2V182M/+ mice revealed frequent myoclonic jerks, and infrequent
generalized tonic-clonic and partial motor seizures. Our results demonstrate that variants in
Scn2a and Kcnq2 can dramatically influence severity of the Scn1aR1648H/+ phenotype. These
studies demonstrate that variants in neuronal ion channel genes can modify the GEFS+
phenotype in a mouse model. This suggests that genetic interactions between ion channel
variants may contribute to clinical variation in patients with inherited epilepsy.
Keywords: epilepsy, ion channels, GEFS, genetics, animal models
38. Object Play as a Moderator of Intervention Effects on
Responding to Joint Attention in Children with ASD
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Rebecca Lieberman, Graduate Student
Authors: Rebecca Lieberman, Allison Nahmias, Seniz Celimli, Daniel Messinger,
Wendy Stone, Ph.D., Alice Carter, Paul Yoder, Ph.D.
Lab P.I. or Faculty Mentor: Paul Yoder, Ph.D.
Department or Program: Special Education
Children with autism spectrum disorders (ASD) may demonstrate deficits in responding to
bids for joint attention (RJA). Flexible and consistent allocation of attention may allow
children to map adult linguistic input more accurately to objects to which their attention has
been drawn. Previous findings suggest children with ASD who are more competent
responders to bids for joint attention may make larger language gains over time. Early
prelinguistic skills such as RJA are important targets for early intervention.
Many early intervention strategies are implemented during play involving objects. A child’s
knowledge of objects may influence their ability to engage in triadic interactions and access
the content of interventions. As children become competent in object knowledge, they may
direct more cognitive resources to new skills, such as RJA.
The current study examined whether object knowledge moderated the effects of a parentmediated social-communication intervention (More Than Words [MTW]) on frequency of
RJA acts in young children with ASD.
Forty-five out of 63 children from a multi-site, randomized controlled trial had analyzable
data. Twenty-three children were randomized to the control group; 22 were randomized to
intervention. Object knowledge was measured pretreatment using the Developmental Play
Assessment. Responding to joint attention was measured at five months follow up using the
Early Social Communication Scales (ESCS). The ESCS was administered by an unfamiliar
examiner using different materials, setting, and interactional style, providing a measure of
far generalization of RJA skills.
Findings indicate treatment led to changes in RJA conditional upon pretreatment object
knowledge (t(45) = -2.60, p = .013). Children with lower levels of object knowledge showed
greater gains in RJA when assigned to treatment; children with higher levels of object
knowledge showed greater gains in RJA when assigned to the control condition.
Children with lower levels of object knowledge may have experienced increases in object
knowledge due to treatment, which allowed greater access to intervention strategies
targeting RJA. It is not yet understood why children with more play skills showed greater
gains in RJA when assigned to the control condition. These findings highlight the
importance of research into child characteristics influencing effects of treatment.
Keywords: autism spectrum disorders, play, RJA, early intervention
39. Orexin Receptor Antagonists Attenuate YohimbineInduced Impairment of Extinction of Cocaine-Conditioned
Place Preference and Excitatory Transmission in the Bed
Nucleus of the Stria Terminalis (BNST)
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Kelly Conrad, Ph.D., Postdoctoral Fellow
Authors: Kelly Conrad, Ph.D., A. Davis, Y. Silberman, D. Sheffler, H. Matthies, S.
Saleh, C. Lindsley, Danny Winder, Ph.D.
Lab P.I. or Faculty Mentor: Danny Winder, Ph.D.
Department or Program: Molecular Physiology and Biophysics
Yohimbine is a widely used pharmacological stressor that is thought to act via its inhibition
of noradrenergic autoreceptors (2-adrenergic receptors, 2-ARs). Recent research has
demonstrated that yohimbine 1) impairs extinction of cocaine conditioned place preference
(cocaine CPP) in C57Bl/6J as well as 2a-AR knockout mice, 2) impairs extinction of cocaine
self administration in rats, and 3) increases alcohol self administration. In acute brain slices
containing the bed nucleus of the stria terminalis (BNST), yohimbine has been shown to
depress excitatory transmission. However, these effects of yohimbine are intact in 2a-AR
knockout mice and not fully mimicked by the more selective 2-AR antagonist atipamezole,
suggesting that they are mediated by targets other than 2-ARs. Recent studies using
yohimbine have proposed an interaction between the noradrenergic and orexinergic
systems. Thus, the purpose of this study was to assess the potential role of orexin receptors
in the actions of yohimbine on reward-related behavior as well as synaptic function in the
BNST. Wildtype and 2a-AR knockout mice were trained in the cocaine CPP paradigm and
the effects of the orexin receptor antagonist, SB-334867, on yohimbine-impaired extinction
were investigated. The effects of SB-334867 as well as a newly synthesized specific orexin
receptor antagonist, 2-{4-{5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1yl}quinazoline (MTBDQ), on yohimbine-induced depression of excitatory transmission in
the BNST were also examined. Our results indicate that SB-334867 attenuated yohimbineinduced impairment of extinction. In addition, both SB-334867 and MTBDQ had no effect
on excitatory transmission but blocked yohimbine-induced depression in BNST field
potential recordings. Taken together, these results suggest that the orexin signaling system
may be a direct target for the actions of yohimbine on reward related behaviors and
excitatory transmission in the BNST.
Keywords: orexin, bed nucleus of the stria terminalis, long-term potentiation, cocaine, Yohimbine
4o. The Role of C-Terminus of HSC70 Interacting Protein in
Mediating Response to Acute Ischemic Injury
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Alixandra Kale, Undergraduate Student
Authors: Cozette Kale, Jeannette Stankowski, Amy Palubinsky, BethAnn
McLaughlin, Ph.D.
Lab P.I. or Faculty Mentor: BethAnn McLaughlin, Ph.D.
Department or Program: Neurology
Stroke is one of the most prevalent neurological disorders in the United States, serving as
the primary cause of long-term, adult disability as well as the third leading cause of death. In
2009 the American Heart Association Statistics Committee and Stroke Statistics
Subcommittee reported that disabled, adult stroke patients alone accumulated $68.9 billion
in health care costs. Within the first hours of oxygen and glucose deprivation, an increase in
reactive oxygen species and a loss of the major intracellular antioxidant, glutathione, result
in protein injury and increased protein misfolding. Specifically, Hsp70 is the major stress
inducible neuroprotective protein upregulated in stroke that can either refold oxidized
proteins or signal for their degradation. Binding with the E3 ubiquitin ligase, C-terminus
HSC70 interacting protein (CHIP), causes client protein degradation. Moreover, CHIP
regulates both the upregulation of Hsp 70 as well as its degradation, suggesting that this
protein plays an essential role in determining cell fate in response to injury. The goal of this
work was to evaluate the neurodevelopmental expression of CHIP and to evaluate if CHIP
deficiency alters responsiveness to CNS stress. Furthermore, we have found that CHIP is
enriched in stroke prone regions such as the cortex, hippocampus and striatum. In addition,
in our oxygen glucose deprivation (OGD) in vitro studies, we found that the overexpression
of CHIP during instances of acute neurological stress, such as ischemic stroke, is in fact
detrimental to cell survival. We have also found, however, that CHIP deficiency alone results
in increased levels of total oxidized proteins in both CNS and peripheral tissue. These
studies can lead to new and better understandings of potential therapeutic targets for
treatment of ischemic injury.
Keywords: ischemic injury, E3 ubiquitin ligase, C-terminus of HSC70 interacting protein, HSP 70
41. Tetracycline-Regulated Corticotropin-Releasing Hormone
Expression in Transgenic Mice as a Model for Isolating BrainRegion Specific Function in the Stress Response
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Gloria Laryea, Graduate Student
Authors: Gloria Laryea, Louis Muglia, Ph.D., M.D.
Lab P.I. or Faculty Mentor: Louis Muglia, Ph.D., M.D.
Department or Program: Neuroscience Graduate Program
Stress initiates or exacerbates psychiatric disorders such as depression and anxiety, and
increases the risk of cancer, heart attack and stroke. The hypothalamic-pituitary-adrenal
(HPA) axis is one of the pathways that mediate the stress response, and does so by
increasing CRH in the limbic system. The central nucleus of the amygdala (CeA) is a known
mediator of behavioral response to stress, anxiety and fear and is the major output region of
the amygdala. The CeA also has the highest concentration of CRH in the brain and has
effects on the HPA axis as well as autonomic output. Previous research shows that CeA CRH
mediates the consolidation of contextual fear memory. Here, we over-express CRH in the
CeA of transgenic mice as a model of stress, isolating only amygdala function in the
response. We also investigate the effects of forebrain CRH over-expression on anxietyrelated behavior. This study uses stereotaxic injections of lentiviral reverse tetracycline
transactivator into the CeA of transgenic mice with the CRH gene under the control of the
tetracycline responsive promoter to over-express corticotropin-releasing hormone (CRH).
Effects of this overexpression were evaluated in fear-based learning tests, as well as anxiety
and despair behavioral tests.
Preliminary behavioral data suggest that CeA CRH plays a role in contextual fear
conditioning. Contrary to expectation, we find decreased learning. Future studies will test
whether chronic CRH overexpression leads to down-regulation of CRH responses at this
brain site.
Keywords: corticotropin-releasing hormone, stress, tetracycline-inducible system, stereotaxic
injections
42. Affective Biological Motion Recognition in Schizophrenia
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Joel Peterman, Graduate Student
Authors: Joel Peterman, M. Giese, A. Christensen, Sohee Park, Ph.D.
Lab P.I. or Faculty Mentor: Sohee Park, Ph.D.
Department or Program: Psychology
Individuals with schizophrenia (SZ) consistently show impairment of facial emotion
recognition, but underlying mechanisms that give rise to this difficulty have not been
elucidated. Given the findings of abnormalities in the fusiform face area and deficits of visual
information processing in SZ, it is possible that these patients may have a perceptual
difficulty in extracting appropriate affective cues from visual stimuli. We thus investigated
the potential perceptual underpinnings of this emotion recognition deficit. The human face
and body are rich sources of social and emotional cues, but only the face stimuli have been
used to examine emotion processing in SZ. Past studies have found that healthy individuals
can accurately detect social information such as personality traits, gender, and affect from
sparse, point-light displays that depict humans in motion (i.e. biological motion). Yet very
little data exist on the role of biological motion perception in affect recognition in SZ. In the
present study, we examined the ability to detect social cues from gait patterns presented by
computer-generated volumetric walking figures. We hypothesized that SZ patients would
show deficits in extracting affective cues from biological motion and that this difficulty might
be associated with social deficits. Outpatients with SZ and demographically matched healthy
controls (CO) viewed 1-second video clips of a “digital” walker in motion. In the Affect
condition they were asked to decide whether the walker is angry or happy in a forced-choice
task. In the Gender condition, they were asked to judge whether the walker is a male or a
female. For each category (e.g. Happy Female), there were 3 levels of intensity. A previous
study validated the stimuli on their intended affect and traits. Overall accuracy and bias were
measured. Clinical symptoms (SAPS, SANS) and social functioning (SFS), mood (PANAS)
and the Theory of Mind (Eyes Test) were also assessed. SZ patients were less accurate and
less sensitive than CO on the Affect condition but similar on the Gender condition. Neither
group differed in their response bias to the stimuli in either condition. These results suggest
that SZ patients are impaired in extracting affective information from biological stimuli and
that this deficit may cascade into misinterpretation of social signals in the real world.
Keywords: schizophrenia, affect, social cognition
43. Astrocytes, Glutamate, and Dendritic Spines in
Schizophrenia
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Peter Vollbrecht, Graduate Student
Authors: Peter Vollbrecht, Huidong Wang, Ariel Deutch, Ph.D.
Lab P.I. or Faculty Mentor: Ariel Deutch, Ph.D.
Department or Program: Neuroscience Graduate Program
Dystrophic changes in the dendrites of pyramidal cells are present in the prefrontal cortex
(PFC) in schizophrenia. These structural changes may contribute to cognitive deficits in the
illness. Dopamine plays an important role in PFC function, with changes in dopamine tone
in the PFC contributing to deficits in including working memory, attention, and executive
function, all of which are impacted in schizophrenia. We have previously shown that
dopamine denervation of the PFC causes dystrophic changes in PFC pyramidal cells,
including a decrease in dendritic spine density. However, the mechanism by which
decreased dopamine leads to decreased dendritic spine number is unclear.
Glutamate plays a critical role in determining dendritic spine development and
maintenance, and changes in glutamatergic transmission in the PFC figure prominently in
current concepts of the pathophysiology of schizophrenia. We show here that dopamine loss
in the PFC causes changes in the expression of proteins involved in glutamate homeostasis,
including GLT-1 and mGluR2/3. The changes we observe in GLT-1 and mGluR2/3 levels are
consistent with a decrease in extracellular glutamate levels. We hypothesize that dopamine
depletion causes changes in extracellular glutamate levels that culminate in dendritic spine
loss.
Keywords: schizophrenia, dopamine, glutamate, dendritic spines, prefrontal cortex
44. Cognitive Relationships Between Nonsymbolic
Enumeration and Symbolic Math Fluency
Cognitive, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Gillian Starkey, Graduate Student
Authors: Gillian Starkey, Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
Functional neuroimaging studies of symbolic arithmetic skill development indicate a
developmental shift from frontal to parietal activity with increasing math fluency (Rivera et
al., 2005), yet such developments are critically dependent on earlier cognitive developments
in exact enumeration skills (Barth et al., 2005). The present study investigates two forms of
cognitive development supporting fluency in nonsymbolic exact enumeration: the ability to
sequentially enumerate random arrays, versus the ability to more rapidly enumerate arrays
arranged in subgroups such that early arithmetic insights can facilitate enumeration.
Although previous fMRI studies in adults suggest both abilities are subsumed by the same
cortical systems (Piazza et al, 2002), these abilities are likely dissociated in cognitive
development of number skills. In the present study, children in kindergarten through third
grade were asked to enumerate random and grouped arrays of dots while naming latencies
were recorded. Enumeration was facilitated for grouped relative to random arrays, as
evidenced by discrepancies between enumeration latencies for the two types of stimuli.
Furthermore, this facilitation increased with age, and correlated with children’s fluency
scores in symbolic arithmetic. This paradigm lays the basis of novel developmental
neuroimaging research to explore the neural correlates of nonsymbolic exact enumeration in
children.
Keywords: numeracy, elementary school
45. Temporal Multisensory Processing: An Event-Related
Potential Analysis
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Leslie Kwakye, Graduate Student
Authors: Leslie Kwakye, Mark Wallace, Ph.D.
Lab P.I. or Faculty Mentor: Mark Wallace, Ph.D.
Department or Program: Neuroscience Graduate Program
We receive information from all our senses that allows us to respond quickly and accurately
to external events. The benefit of multisensory stimuli is crucially dependent on the
temporal structure of the component unisensory stimuli. The neural networks that underlie
this temporal dependence have not been fully elucidated. Previous research has shown that
participants respond faster to simultaneous audiovisual stimuli than would be predicted by
the race model. The event-related potential (ERP) waveform produced in response to
audiovisual stimuli differs from the summed unisensory waveforms at several time points
and scalp locations. By introducing temporal disparities of varying durations we can observe
how the well-characterized behavioral and electrophysiological effects are altered by the
temporal structure of the audiovisual stimuli. Preliminary findings suggest that the
multisensory ERP waveform resulting from short SOAs (100 ms) show similar deviations
from the summed unisensory waveform. Longer SOAs (200 and 400 ms) resulted in a
different pattern of deviations from the summed unisensory waveform (particularly a
marked sub-additivity around 300 ms) indicating a change in the multisensory network that
underlies this behavioral benefit. Future analyses will focus on characterizing these key
changes to further increase of understanding of the networks that subserve temporal
multisensory processing.
Keywords: multisensory integration, ERP, temporal processing
46. Gulping Up Some Death: The Interaction of the Adaptor
Protein Gulp with Engulfment Receptors Jedi-1 and MEGF10
in Neuronal Corpse Clearance
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Rajan Dang, Undergraduate Student
Authors: Rajan Dang, Jami Scheib, Chelsea Cupp, Bruce Carter, Ph.D.
Lab P.I. or Faculty Mentor: Bruce Carter, Ph.D.
Department or Program: Biochemistry
During development, approximately half of developing neurons in the peripheral nervous
system undergo apoptosis as part of a normal pruning process. These corpses need to be
cleared in order to prevent an inflammatory response and the possible development of
autoimmunity. We have recently shown that apoptotic neurons in the developing
mammalian dorsal root ganglia are cleared by satellite glial cell (SCG) precursors; moreover,
Jedi-1 and MEGF10 have been identified as engulfment receptors on the membranes of SCG
precursors involved in phagocytosis. The adaptor protein Gulp may also be involved in this
process, as its homolog in C. elegans, Ced-6, interacts with the engulfment receptor Ced-1,
which is homologous to Jedi-1 and MEGF10. In particular, Ced-6 interacts with Ced-1
through an NPXY domain on Ced-1; Jedi-1 and MEGF10 also have NPXY domains.
Furthermore, like Ced-6, Gulp has a phosphotyrosine-binding domain, which binds to NPXY
domains. Engulfment assays have shown that a mutation in the NPXY domain (NPXY 
NPXF) on Jedi-1 or MEGF10 reduces engulfment. Also, preliminary coimmunoprecipitation data shows that Gulp binds to Jedi-1 and MEGF10. We are still
investigating Gulp and Jed-1 / MEGF10 association, as well as mapping these interactions.
Also, we plan to explore the role of Gulp in engulfment through shRNA knockdown. Because
Ced-6 binds to Ced-1 through an NPXY domain, and thus plays a critical role in engulfment,
we predict that Gulp plays a similar role in mammalian cells through interaction with the
engulfment receptors Jedi-1 and MEGF10 via the NPXY domain.
Keywords: engulfment, Jedi-1, MEGF10, Gulp
47. Relative Quantitation and High-Resolution Mass
Spectrometry Imaging of Cholesterol and
7-Dehydrocholesterol Oxysterols in Smith-Lemli-Opitz
Syndrome Mouse Model
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Michal Kliman, Graduate Student
Authors: Michal Kliman, Zeljka Korade, Ph.D., Libin Xu, Ph.D., John McLean, Ned
Porter, Ph.D.
Lab P.I. or Faculty Mentor: Zeljka Korade, Ph.D., Ned Porter, Ph.D.
Department or Program: Chemistry
In human Smith-Lemli-Opitz Syndrome (SLOS), mutations in the gene encoding 7dehydrocholesterol reductase (Dhcr7) enzyme, which catalyzes the conversion of 7dehydrocholesterol (7-DHC) to cholesterol, lead to elevated levels of 7-DHC and reduced
level of cholesterol in tissues and fluids. The symptoms of SLOS include incomplete
myelination, developmental defects, and autism-like mental impairment. Recently, oxidative
metabolites of 7-DHC, i.e., oxysterols, that were identified in the nervous tissue of SLOS
mice and human fibroblasts, were shown to be potentially critical in the pathophysiological
changes seen in SLOS. Using mass spectrometry imaging and relative quantitation, we
confirmed drastic differences in cholesterol, 7-dehydrocholesterol and its oxysterols
distributions between normal and knock-out mouse SLOS model brain tissues. We are
developing sample preparation methodologies and high resolution imaging approaches to
follow the spatial distributions of these metabolites in SLOS tissues.
Keywords: SLOS, cholesterol, spectrometry, quantitation, imaging
48. Role of Alpha-Actinin in Modulating CaMKII-Dependent
Regulation of NMDA Receptors
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Nidhi Jalan-Sakrikar, Graduate Student
Authors: Nidhi Jalan-Sakrikar, Roger Colbran, Ph.D.
Lab P.I. or Faculty Mentor: Roger Colbran, Ph.D.
Department or Program: Molecular Physiology and Biophysics
Ca2+/Calmodulin-dependent protein kinase II (CaMKII), a downstream mediator of Ca2+signaling is critical for synaptic plasticity, learning and memory. Ca2+ influx causes
Ca2+/calmodulin (CaM)-dependent activation of CaMKII and transient translocation of
cytosolic CaMKII to the postsynaptic density (PSD). Activated CaMKII binds to and
phosphorylates NR2B at S1303 to enhance NMDAR desensitization (Sessoms-Sikes et al.
2005 Mol Cell Neurosci. 29: 139). Moreover, CaMKII binding to the NR2B subunit of NMDA
receptors (NMDARs) is essential for normal synaptic plasticity. However, the molecular
mechanisms underlying dynamic translocation of CaMKII to PSDs are incompletely
understood. Clustering of both CaMKII and -actinin-2 at synapses was previously shown
to be dependent on the F-actin cytoskeleton (Allison et al. 2000 J Neurosci. 20: 4545) and
-actinin and CaMKII independently interact with NR2B. -Actinin is a F-actin binding
protein that directly interacts with CaMKII competitively with Ca2+/CaM. The structure of
Ca2+/CaM bound to CaMKII regulatory domain peptide (PDB: 1CM1) is similar to that of actinin-2 bound to titin kinase (PDB: 1H8B). Thus, we hypothesized that -actinin at least
partially mimics Ca2+/CaM in binding to CaMKII. Indeed, mutations in the CaMKII
regulatory helix that disrupt binding of Ca2+/CaM also affect the Ca2+-independent
interaction with -actinin-2. However, unlike CaM, which fully activates CaMKII only in
presence of Ca2+, -actinin-2 can partially activate CaMKII phosphorylation of S1303 in
NR2B independent of Ca2+ in vitro. Based on the crystal structures, we also made mutations
in the CaMKII binding domain of -actinin-2. These mutations disrupt the interaction with
CaMKII, both in vitro and in HEK293 cells. -Actinin, NR2B and CaMKII can be coimmunoprecipitated in the same complex from mouse brain. Preliminary studies indicate
that -actinin can enhance the interaction of CaMKII with NR2B in HEK293 cells.
Mutations in the C-terminal domain of -actinin that disrupt CaMKII binding also reduce
the association of CaMKII with NR2B in HEK293 cells. Currently, we are investigating the
role of -actinin in regulating CaMKII interaction with NR2B and phosphorylation at S1303
in NR2B in the whole NMDAR. These studies will improve our understanding of the role of
-actinin in regulating CaMKII activation and the interaction with NMDAR, and thus the
modulation of synaptic plasticity.
Keywords: CaMKII, alpha-actinin, NMDA receptors, signaling, synaptic plasticity
49. Alerting and Executive Attention: Their Interaction on LPC
Amplitude in Children
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Fengji Geng, Graduate Student
Authors: Fengji Geng, Yuzheng Hu, Yunqi Wang, Feiyan Chen
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
The Attention Network Task (ANT) has been used to investigate separate brain networks
associated with alerting and executive functions, as well as to explore how these networks
interact in adults and develop in children. Little is known, however, about how these brain
systems interact during development. This study used event related potential (ERP) to test
how these networks interact in children by examining alerting, cue-target interval (CTI), and
conflict manipulations of the Late Positive Complex (LPC) response. Participants consisted
of 17 children (8 boys, Mean age = 11.15) with 3 excluded from ERP analyses due to technical
problems. Repeated measures ANOVA indicated: (1) With 400-ms CTI children got higher
conflict scores (F (1, 16) = 7.90, p < .02) in trials with cue than without cue; (2) in LPC we
detected the salient effects of Cue (F (1, 13) = 7.79, p < .03), CTI (F (1, 13) = 10.14, p < .01),
Cue × CTI (F (1, 13) = 6.21, p < .04), and Flanker × CTI × Hemisphere (F (1, 13) = 5.91, p <
.04). Planned contrast revealed that with 400-ms CTI the LPC amplitude was larger in trials
with cue than without cue (p < .02); with 100-ms CTI the LPC amplitude in the right
hemisphere was larger in incongruent versus congruent trials (p < .01); with the presence of
cue LPC amplitude was larger in trials with 400-ms versus 100-ms CTI (p < .01). This study
detected the interaction between alerting and executive functions in children under certain
CTI. The strategy in allocating attentional resource rather than the competition for resource
was proposed to interpret this interaction.
Keywords: alerting, executive attention, late positive complexity
50. Guilt Among Adult Siblings of Individuals with
Developmental Disabilities
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Carolyn Shivers, Graduate Student
Authors: Carolyn Shivers, Julie Lounds Taylor, Ph.D., Robert Hodapp, Ph.D.
Lab P.I. or Faculty Mentor: Julie Lounds Taylor, Ph.D., Robert Hodapp, Ph.D.
Department or Program: Developmental Psychology
Though the extant research cites guilt as a possible outcome for typically developing siblings
of individuals with developmental disabilities, no studies have measured levels of guilt or
correlates of guilt among siblings. The present study examines how likely siblings are to
report increased guilt in relation to growing up with a brother or sister with a disability, as
well as factors that are related to increased guilt.
We addressed this question using data from the Adult Siblings’ Questionnaire, a national
web-based survey. A total of 1,021 respondents included individuals from all 50 states, with
an age range of 18 to 85.
The variable of interest was taken from a single question asking how participants’ level of
guilt has changed as the result of growing up with a brother or sister with a disability.
Variables related to the following constructs were analyzed to determine their relationship
with sibling guilt: sibling relationship; characteristics of the brother/sister with a disability;
characteristics of the sibling; future caregiving. Responses to two open-ended questions
were coded for qualitative analysis: 1) What would help you now to better support your
brother or sister with a disability, and 2) What would have helped you growing up as a
sibling of a child with disabilities?
Initial analyses determined that 53% of siblings reported an increase in guilt. Multivariate
analyses showed that increased guilt was predicted by the following variables: lower sibling
relationship quality, fewer brother/sister functional abilities, increased brother/sister
behavioral problems, higher percentage of brother/sister unmet service needs, more sibling
plans for future caregiving, and female sibling gender. Analyses of responses to open-ended
questions showed that siblings reporting increased guilt were more likely to cite needs for
personal support and improvements on the part of their family.
These findings suggest that guilt is a relatively common emotion among siblings of
individuals with disabilities. Quantitative analyses showed that characteristics of the
brother/sister with disabilities, quality of the sibling relationship, and plans for future
caregiving were all related to guilt. Qualitative analyses suggest that additional family factors
may also be important in the development of guilt.
Keywords: guilt, families, siblings
51. Negative Cognitive Style and Coping with Stress in
Children of Depressed Parents
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Jennifer Potts, Graduate Student
Authors: Jennifer Potts, Laura McKee, Rex Forehand, Jennifer Champion, Bruce
Compas, Ph.D.
Lab P.I. or Faculty Mentor: Bruce Compas, Ph.D.
Department or Program: Psychology and Human Development
Parental depression is a major risk factor for depression and psychopathology in children (Jaser et al.,
2005). Two sources of individual differences in the risk for depression are negative cognitive style and
how children cope with the stress of living with a depressed parent. Negative cognitive style includes
attributing causes of negative events to global and stable sources and expecting future adverse
outcomes (Hankin & Abramson, 2002). Negative cognitive style accounts for a portion of the variance
in depressive symptoms in children of depressed parents (Morris et al., 2008). Conversely, in
response to stressful interactions with their depressed parents, children’s secondary control coping
(acceptance, reappraisal, distraction) is related to fewer depressive symptoms (Jaser et al., 2008).
Previous research has examined these sources of individual differences independently, but
understanding their relative contributions to depressive symptoms in children of depressed parents is
also significant.
The current study examines how negative cognitive style and secondary control coping contribute to
depressive symptoms in 166 9-to-15-year-old children of depressed parents. Parents had at least one
depressive episode (Mdn=4) in their child’s lifetime, diagnosed by the SCID. Children’s depression
was assessed via parent and child reports on the K-SADS (2.85 mean depression symptoms endorsed)
and a composite of the YSR and CBCL Affective Problems Scale (Achenbach & Rescorla, 2001). The
ACSQ (Hankin & Abramson, 2002) assessed children’s negative cognitive style, and a composite of
parent and child reports on the RSQ (Connor-Smith et al., 2000) measured children’s secondary
control coping.
Children’s negative cognitive style correlated positively with depressive symptoms (Affective
Problems Scale: r=.36, p<.001; K-SADS: r=.27; p<.001), and children’s secondary control coping
correlated negatively with depressive symptoms (Affective Problems scale: r=-.50, p<.001; K-SADS:
r=-.35, p<.001). Children’s secondary control coping correlated negatively with negative cognitive
style (r=-.20, p<.05).
In regression analyses, negative cognitive style (=.27, p<.001) and secondary control coping (=-.45,
p<.001) were independent predictors of children’s depressive symptoms on the Affective Problems
Scale. Similar results occurred using the K-SADS as the dependent variable (=.21, p<.01 ; =-.31,
p<.001). Therefore, at higher levels of negative cognitive style and at lower levels of secondary control
coping, children and their parents report higher levels of children’s depressive symptoms via
questionnaires and structured clinical interviews.
This study replicates prior findings of negative cognitive style and secondary control coping predicting
depressive symptoms in children of depressed parents and provides the first evidence that negative
cognitive style is related to poorer coping (less secondary control coping). Although negative cognitive
style and secondary control coping are correlated, they independently predict depressive symptoms.
This suggests two avenues for prevention in this high-risk population—decreasing negative cognitions
and enhancing secondary control coping can potentially prevent depressive symptoms in children of
depressed parents.
Keywords: coping, negative cognitive style, depression
52. Disrupted Thalamic Physiology in Angelman Syndrome:
The Role of GABAergic Signaling
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Mark Grier, Graduate Student
Authors: Mark Grier, Carl Weitlauf, Lisa Herrington, Kevin Haas, Andre Lagrange
Lab P.I. or Faculty Mentor: Kevin Haas, Ph.D., M.D., Andre Lagrange, Ph.D., M.D.
Department or Program: Pharmacology
Angelman syndrome (AS) is a neurogenetic disorder associated with profound intellectual
disability, sleep disturbances and refractory epilepsy. AS results from a neuronal deficiency
of functional UBE3A (also known as E6-AP), an E3 ubiquitin ligase encoded by the UBE3A
gene. The seizure types, sleep disturbances, and EEG changes seen in AS suggest that
dysfunction of thalamocortical circuitry plays a prominent role in the phenotype. In
maternal Ube3a knockout (AS) mice, we have shown that Ube3a expression is imprinted in
reticular nucleus (nRT) and ventrobasal (VB) nucleus neurons of the thalamus.
Intrathalamic GABAergic inihbition plays a key role in generating both normal sleep and
generalized seizures. To begin to understand the role of Ube3a in regulating thalamocortical
function, we evaluated GABA-A receptor (GABAR) expression and function in AS and wildtype (WT) mice. GABARs are pentameric receptors composed primarily of a combination of
α, β and either a δ or γ subunits. Most subunits have multiple isoforms, which is a key
determinant of GABAR function.. Immunoblotsfound increased α4 and δ GABAR subunit
expression in the thalamus of P17-28 AS mice relative to WT littermates. Whole cell patchclamp recordings from acute thalamic slices (P8-21) detected alterations in the
developmental profile of spontaneous GABAR-mediated transmission. Additionally, we
tested the response of GABAergic transmission to α4 and δ subunit subtype-preferring
agents including Ro15-4513 and DS2. The response to DS2, an 4δ preferring drug, was
unchanged in neurons from AS mice. Ro15-4513 is a benzodiazepine-like drug that inhibits
(1,2,3,or 5) receptors but enhances 42 GABAR responses. While this drug had no
effect on VB neurons, Ro15-4513 application to WT nRT neurons decreased decay time and
charge transfer, which is predicted to lead to intra-thalamic disinhibition. Consistently, we
found that sIPSC frequency in this region was increased by Ro15-4513. In contrast, Ro154513 application to AS nRT neurons lead to increased IPSC amplitude, with a blunted
reduction in decay time resulting in no overall change in change transfer or disinhibition.
Our findings suggest that altered thalamic GABAR subunit expression contribute to
thalamocortical dysfunction in AS and will help to inform the development of new
treatments for this devastating disorder.
Keywords: Angelman syndrome, epilepsy, GABA receptors
53. Sex Differences in the Effects of Depression Prevention
Programs
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Lindsay Downs, Graduate Student
Authors: Lindsay Downs, Judy Garber, Ph.D.
Lab P.I. or Faculty Mentor: Judy Garber, Ph.D.
Department or Program: Psychology and Human Development
Several recent qualitative and quantitative reviews of depression prevention programs in youth have
reported low to moderate effect sizes (EF). Few reviews, however, have examined sex differences in
the effects of these prevention programs. The present meta-analysis evaluated the effects of targeted
(selective and indicated) and universal depression prevention programs by sex and intervention type.
Data were available by sex for 23 studies (22 EFs for females, 19 for males) at post-test, and from 22
studies at follow-up (22 for females, 18 for males). Of those studies, 14 used targeted samples and 9
were with universal samples. Unbiased weighted EFs were computed for self-report measures of
depressive symptoms, the most common being the Children’s Depression Inventory (i.e., used in
11/24 studies). ESs for each study were calculated for each sex by dividing the post-intervention
difference between the control group and intervention group scores by the pooled standard deviation
of the groups. Between-groups meta-ANOVAs were conducted comparing the weighted mean EF for
males and females at post-test and follow-up (closest to 6 mo.). Finally, separate analyses were run
for studies using targeted samples only.
Across targeted and universal samples at post-test, the weighted mean ES for females in 22 studies
was 0.17 (95% CI 0.11-0.24), which was significantly different from zero (z = 5.06, p< 0.001); for
males in 19 samples, the mean ES was 0.22 (95% CI 0.14-0.29), which also was significantly different
from zero (z=5.37, p< 0.001). At follow-up, the mean ES for females (N=22) was 0.08 (95% CI 0.010.15), significantly different from zero (z=2.28, p=.02); the mean ES for males (N=18) was 0.20 (95%
CI 0.12-0.28), also significantly different from zero (z=4.71, p<0.001). At post-test, meta-ANOVA
analyses revealed that there were no significant differences in ES by sex (QB= 0.56; df =1; p=.46). At
follow-up, the mean ES was significantly higher for males than for females (QB= 4.53; df=1; p=.03).
Within targeted samples at post-test, the weighted mean ES for females across 13 studies was 0.18
(95% CI 0.09-0.28), and significantly different from zero (z=5.03, p<0.001); for males across 12
studies, the mean ES was 0.12 (95% CI 0.01 - 0.24), significantly different from zero (z = 2.11, p =
.03). At follow-up, the mean ES for females was 0.04 (95% CI -0.05 - 0.14), which was not different
from zero (z = 0.91, p = .36); for males the mean ES was 0.23 (95% CI 0.11 - 0.34), which was
significantly different from zero (z = 3.84, p<0.001). At post-test, meta-ANOVA analyses revealed
that there were no significant differences in outcome by sex (QB= 0.62; df=1; p=.43). At follow-up,
the mean ES was significantly higher for males than for females (QB= 5.8; df=1; p=.016).
Overall, mean effect sizes were moderate for both males and females at post-test in targeted and
universal samples, with no significant differences as a function of sex. At follow-up, the mean effect
size for males was significantly higher. This pattern was similar when analyses were conducted for
studies using targeted programs only.
Keywords: depression, gender
54. Human iPSC-Derived Neural Progenitors Demonstrate
Patient-Specific Vulnerability to Copper Toxicity
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenters: Andrew Tidball, Graduate Student, and Asad Aboud, M.D., Postdoctoral
Fellow
Authors: Andrew Tidball, Asad Aboud, M.D., Diana Neely, Ph.D., Gary Li, Michael
Litt, Kevin Ess, Ph.D., M.D., Aaron Bowman, Ph.D.
Lab P.I. or Faculty Mentor: Diana Neely, Ph.D., Kevin Ess, Ph.D., M.D., Aaron
Bowman, Ph.D.
Department or Program: Neurology
Although heavy metals, lead and mercury, along with some organic compounds have been
discovered to be developmental neurotoxicants, the difficulty in obtaining developing
human neural tissue has made it difficult to screen for additional toxicants and the
concentrations at which they become harmful. Additionally, environmental toxicants are
thought to interact with genetic disease mechanisms potentially increasing severity or
producing earlier age-at-onset. We utilize induced-pluripotent stem cells differentiated into
PAX6+ neural progenitors as a model of patient-specific neurotoxicity. Using lines generated
from control individuals and patients with familial Parkinson’s disease (PARK2 -/-) and
Tuberous Sclerosis Complex, we have measured cell viability at increasing concentrations of
metals including cadmium, copper, manganese, and methylmercury. We found a statistically
significant difference in the cell viability of neural progenitors between patients based on
calculated EC50 values for copper. These differences remained constant after comparing
multiple clonal iPSC lines from each patient indicating a potential gene-environment
interaction. The establishment of this screening protocol will allow the identification of
potential neurotoxicants, toxicological variability due to individuals’ genetic differences, and
potential disease-specific gene-environment interactions. These interactions could play a
role in age-at-onset variability in many hereditary diseases and be targeted for prophylactic
treatment.
Andrew Tidball and Asad Aboud contributed equally to this project.
Keywords: neurotoxicity, induced pluripotent stem cells, gene-environment interaction, Parkinson’s
disease, Tuberous Sclerosis
55. The Effect of Intellectual Ability on Functional Brain
Activation in Williams Syndrome: An fMRI Study
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Jennifer Pryweller, Graduate Student
Authors: Jennifer Pryweller, Elisabeth Dykens, Ph.D., Tricia Thornton-Wells, Ph.D.
Lab P.I. or Faculty Mentor: Tricia Thornton-Wells, Ph.D.
Department or Program: Interdisciplinary Studies: Neuroimaging of
Neurodevelopmental Disorders
Introduction: Williams Syndrome (WS) is a rare genetic disorder caused by the deletion of
~26 genes on chromosome 7q11.23 and is characterized by mild to moderate intellectual
disability (ID), although some individuals with WS have normal intelligence and some have
severe ID. People with WS or other developmental disorders who have ID have been
excluded from functional neuroimaging studies based on the assumption that low IQ is
associated with substantially higher functional activation in the brain. If this were true, IQ
would be a confounding factor, limiting the ability of the researcher to attribute group
differences in brain activation to the particular task or behavior under study. We aimed to
test the status quo hypothesis that IQ is correlated with brain activation.
Methods: Participants included 16 subjects with WS (age [meanSD]: 27.110.1; 6 females,
10 males), demonstrating a range of standardized IQ scores ([range, meanSD] composite
IQ: 40-102, 69.320.9; verbal IQ: 40-107, 76.318.7; non-verbal IQ: 40-98, 67.621.6). We
measured blood-oxygenation level dependent (BOLD) response during passive listening
tasks in each of 30 anatomically defined regions of interest (ROIs) across the whole brain in
each individual and correlated those measures with composite, verbal and non-verbal IQ
scores. We also dichotomized IQ and performed t-tests to evaluate group differences in
BOLD response.
Results: There were no significant group (low vs. high IQ) differences in BOLD response
across 30 ROIs (t-test p < 0.05). There also were no significant correlations (Spearman’s
rho p < 0.05) between BOLD response and composite IQ in any of the 30 ROIs. Nominally
significant (uncorrected p < 0.05) correlations were found for 4 ROIs, although none
support the hypothesis that IQ is negatively correlated with BOLD response.
Discussion: These data suggest that the inclusion of subjects with below normal IQ does
not introduce a confounding factor. By including subjects representative of the range of ID
in the disorder being studied, findings are more likely to generalize to that population.
Ongoing analyses will investigate whether this finding holds for a variety of fMRI studies in
WS, and future work should involve other populations with intellectual and developmental
disabilities.
Keywords: Williams syndrome, intellectual quotient, neuroimaging
56. Genetic Inhibition of Dorsal Striatal CaMKII Generates
“Silent” Synapses on Medium Spiny Neurons and Deficits in
Striatal-Based Learning
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Jason Klug, Graduate Student
Authors: Jason Klug, T. Kash, C. Olsen, Robert Matthews, Ph.D., A. Robison, E.
Watt, E. Epstein, M. Anderson, Roger Colbran, Ph.D., Danny Winder, Ph.D.
Lab P.I. or Faculty Mentor: Roger Colbran, Ph.D., Danny Winder, Ph.D.
Department or Program: Neuroscience Graduate Program
The striatum plays a key role in both motor and habit learning and pathological disruptions
in this brain region have been implicated in drug addiction, Huntington’s disease and
Parkinson’s disease. Activity-dependent changes in synaptic strength are postulated as a
neural correlate of learning and memory. Deletion of striatal NMDA receptors disrupts
motor learning and synaptic plasticity. Downstream of NMDA receptor activation,
Ca2+/calmodulin-dependent protein kinase II (CaMKII), present at high levels in
glutamatergic synapses, is an important player in the induction of NMDA receptordependent long-term potentiation (LTP) and in regulating the dynamics of glutamatergic
synapses. However, little is known about how CaMKII modulates glutamatergic synaptic
transmission in the striatum. Therefore, we are studying glutamatergic synapses in a
transgenic mouse strain expressing a pseudosubstrate inhibitor peptide fused to EGFP
(EAC3I) that can inhibit both calcium-dependent and independent CaMKII activity. The
EAC3I transgene is expressed with a mosaic pattern in both direct and indirect pathway
medium spiny neurons (MSNs) in the dorsal striatum, though expression in the ventral
striatum is very low. Consistent with minimal expression in the accumbens, cocaine-induced
locomotor sensitization was unaltered in these mice. However, EAC3I expressing mice
compared to controls have deficits in random ratio responding for food, a behavioral assay
that has been useful to investigate the neural circuits and the cellular and molecular
mechanisms involved in goal-directed actions and habits. Whole-cell voltage clamp
recordings in acute brain slices comparing basal glutamatergic synaptic transmission in
CaMKII-inhibited versus neighboring non-inhibited cells in the dorsal lateral striatum
reveals markedly distinct basal electrophysiological characteristics. Convergent lines of
evidence suggest that EAC3I-expressing cells have greater numbers of “silent” synapses synapses that lack AMPA receptors. In addition, we observed changes in synaptic AMPA
receptor and NMDA receptor current kinetics in CaMKII-inhibited MSNs. These data
suggest that CaMKII inhibition is not only involved in the trafficking of glutamate receptors
at striatal glutamatergic synapses, but may also affect their functional properties. These
findings offer new insights into CaMKII regulation of glutamatergic synapses in the
striatum.
Keywords: striatum, CaMKII, silent synapses, habit learning, GluN2B
57. Attentional Focus While Learning Impacts Perceptual
Expertise for Reading Novel Word Forms: An ERP Training
Study
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Yuliya Yoncheva, Ph.D., Postdoctoral Fellow
Authors: Yuliya Yoncheva, Ph.D., Jessica Wise, Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
Reading instruction can highlight different unit sizes in print-to-speech mappings, ranging
from whole words to grapheme-phoneme relationships within words. Thus, attentional focus
on specific unit sizes during learning might influence the neural mechanisms recruited later
in skilled reading, as indexed by the characteristically left-lateralized N170 event-related
potential (ERP) response. The present study tested this hypothesis by training literate adults
in an artificial writing system consisting of word characters (glyphs) containing embedded
letters. Subjects learned to associate sets of auditory English words with corresponding
glyphs under two instruction conditions. For one set, participants were instructed to focus
on linking entire characters to whole auditory words (whole-word focus); for another set,
they were instructed to focus on linking the embedded letters to the vowels and consonants
within the auditory words (grapheme-phoneme focus). Following training, ERPs to both sets
of glyphs were recorded during a reading verification task. Glyphs trained under graphemephoneme focus elicited a more left-lateralized N170 topography relative to the rightlateralized N170 topography observed in response to glyphs trained under whole-word focus.
These results demonstrate that focusing learners’ attention on certain unit size mappings
can impact the neural circuitry subsequently recruited by specific stimuli during reading.
The current findings support the notion that attentional focus plays a key role in early
reading acquisition.
Keywords: language learning, reading acquisition, selective attention, ERP, N170 lateralization
58. What Is a Successful Transition to Adulthood for
Individuals with Disabilities?
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Natalie Henninger, Undergraduate Student
Authors: Natalie Henninger, Julie Lounds Taylor, Ph.D.
Lab P.I. or Faculty Mentor: Julie Lounds Taylor, Ph.D.
Department or Program: Vanderbilt Kennedy Center
Introduction: Researchers often evaluate the “success” of the transition from adolescence to
adulthood for individuals with disabilities in terms of independence in living and employment and the
development of reciprocal social relationships. The present study surveyed individuals with
disabilities and parents of individuals with disabilities to see which elements of adult outcomes they
see as most important for a successful transition.
Methods: An Internet survey targeting adults and parents of individuals with intellectual,
developmental and physical disabilities was disseminated through various disability networks and
local chapters of disability organizations (n = 85). Basic demographic information was collected, and
participants were asked to rank, in order of importance, 7 elements of transition success (e.g., making
decisions for oneself, having good friends). Participants also answered an open-ended question asking
what they personally consider to be a successful transition.
The sample consisted of 73 parents and 12 adults with disabilities. Nearly all of the parents (93.2%)
were female, and the mean age was 51.5 years (range 34-74). Their son or daughter with a disability
had a mean age of 20.4 years (range 5-45), and the most common diagnosed disabilities were Autism
Spectrum Disorder (43.8%), and Intellectual/Developmental Disability (32.9%). Most (90%) of the
children were residing with the parent. Just over 20% were younger than high school, 22.1% were in
high school, 13.2% were in post-secondary training or college, and 44.1% were done with high school
but not in any post-secondary education. Of the 12 adults with disabilities who responded, 7 were
female, with a mean age of 34 years (range 18-54). The majority (75%) had an
Intellectual/Developmental Disability, and 33.3% had Cerebral Palsy. Seven were currently living
with parents, 4 independently, and 1 in the home of another relative. Three were currently in high
school, 3 were in college, one was out of high school but not in college, and 4 had completed college.
Results: The element of transition success rated as most important was being happy, followed by
making decisions for oneself; having good physical health; working in a job that pays attention to a
person’s interests, strengths, and weaknesses; and having good friends. The two elements ranked
least important were working independently or with supports in community, and living independently
in one’s own house or apartment. When analyzing data based on the type of respondent, parents
placed the most importance on happiness and good physical health, and adults with disabilities
placed the most importance on making decisions for themselves and working independently or with
supports in the community. Responses to the open-ended question about a successful transition
revealed two broad themes: the importance of gaining independence from the family and positively
contributing to society. Common topics of the responses were work, living arrangements,
relationships, and community involvement.
Discussion: Our results indicate that the aspects of the transition to adulthood traditionally
measured (e.g., independence in living and working) may not be most salient for individuals with
disabilities or their families. Additionally, there seem to be differences between what the adult with
disabilities and the parent sees as most important for a successful adult outcome.
Support: Marino Autism Research Institute, NCCR (1 UL1 RR024975), NICHD (P30 HD15052)
Keywords: transition, autism spectrum disorders, adult outcome
59. High-Throughput Assessment of Cellular Manganese (Mn)
Status Suggests Novel Mechanisms Underlying Mn Transport
Deficit in a Striatal Cell and Rodent Models of Huntington’s
Disease
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Gunnar Kwakye, Graduate Student
Authors: Gunnar Kwakye, Olympia Kabobel, Daphne Li, Keith Eriksson, Michael
Aschner, Ph.D., Aaron Bowman, Ph.D.
Lab P.I. or Faculty Mentor: Aaron Bowman, Ph.D.
Department or Program: Neuroscience Graduate Program, Center for Molecular
Toxicology, Neurology
Expression of mutant Huntingtin (Htt) is associated with impaired manganese (Mn)
accumulation in a striatal cell line and mouse models of Huntington’s disease (HD). To
evaluate this mechanism, we have developed and validated a high-throughput fluorescencequenching based assay (Cellular Fura-2 Manganese Extraction Assay - CFMEA) to measure
Mn transport kinetics and storage properties in cultured striatal cells and rodent tissues. We
have applied CFMEA to confirm the impaired Mn uptake observed in mutant striatal cells
following 27 hours Mn exposure. Here, we demonstrate that the impaired Mn phenotype in
mutant striatal cells is observed as early at 1 hour following 200 µM Mn exposure. In
addition, mutant Mn deficit is not dependent on other di or trivalent metals, serum proteins,
or known co-transporter ions in the culture media and exposure buffers. Moreover, mutant
striatal cells’ Mn uptake deficit is independent of the divalent metal transporter 1 (DMT1)
and 2-APB blockable channels. Importantly, mitochondrial function has been reported to be
impaired in mutant striatal cells. Thus, we hypothesized that expression of mutant Htt
would impair the mitochondria regulator functions of metal ion homeostasis via the PPAR
mediated pathway in mutant cells. To test this hypothesis, we utilized PPAR agonist
(rosiglitazone) and antagonist (GW9662) and fail to observe an influence of the PPAR
mediated pathway on the Mn deficit observed in mutant striatal cells. In spite of similar
instantaneous Mn uptake and efflux rates in wildtype and mutant striatal cells, we
demonstrate that there is significant decrease in mutant net Mn storage capacity compared
to wildtype. Finally, we have applied CFMEA in mouse brain tissues to assess temporal and
spatial Mn accumulation. In conclusion, we have demonstrated that the Mn deficit in
mutant striatal cell lines is likely due to impairment in Mn uptake and storage capabilities
rather than efflux.
Keywords: manganese, Huntington’s disease, high-throughput assay, metal transport, Fura2
60. Human and Mouse Neurons Developed from iPSCs as a
Model for Disease Pathogenesis and Drug Discovery in
Angelman Syndrome
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Terry Jo Bichell, Graduate Student
Authors: Terry Jo Bichell, Andrew Tidball, Diana Neely, Ph.D., Bryan Cawthon,
Charles Hong, Aaron Bowman, Ph.D., Kevin Ess, Ph.D., M.D., Kevin Haas, Ph.D.,
M.D.
Lab P.I. or Faculty Mentor: Diana Neely, Ph.D., Aaron Bowman, Ph.D., Kevin Ess,
Ph.D., M.D., Kevin Haas, Ph.D., M.D.
Department or Program: Neuroscience Graduate Program
Angelman syndrome (AS) is a severe neurodevelopmental disorder of imprinting caused by a
deletion or mutation of the ubiquitin protein ligase (UBE3A) gene on the maternally
inherited 15th chromosome. UBE3A is imprinted only in brain, making its action impossible
to study in living humans, except by external studies, such as clinical examinations or MRI
scans. Although many targets of UBE3A have been identified, their contributions to the
mechanisms underlying this disease process are not yet understood, and thus there are
currently no effective treatments for the disease other than palliative care. In order to
elucidate the function of UBE3A and hasten the drug discovery process, new highthroughput assays must be found. We developed induced pluripotent stem cells (iPSCs) from
fibroblasts obtained from human patients with deletion positive AS and normal controls as
well as from Ube3a mutant and wildtype mouse fibroblasts. These cells are then used for
directed differentiation to neurons. This exciting new approach will allow us to make a
comparison of human versus mouse UBE3A/Ube3a gene function and will serve as a
platform for high-throughput drug discovery to hopefully ameliorate the neurological
features seen in people with AS.
Keywords: Angelman syndrome, iPSC, neuronal differentiation, stem cells, drug discovery
61. The Engulfment Receptors Jedi1 and MEGF10 Involved in
Neuronal Corpse Clearance Interact with Syk Gulp and Src
Family Kinases
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Jami Scheib, Graduate Student
Authors: Jami Scheib, Chelsea Cupp, Rajan Dang, Bruce Carter, Ph.D.
Lab P.I. or Faculty Mentor: Bruce Carter, Ph.D.
Department or Program: Neuroscience Graduate Program
Approximately 50% of neurons in the developing peripheral nervous system undergo
apoptosis as part of a normal pruning process. These neuronal corpses need to be cleared in
order to prevent an inflammatory response and the possible development of autoimmunity.
We recently demonstrated that apoptotic neurons in the developing mammalian dorsal root
ganglia are cleared by satellite glial cell (SGC) precursors. Furthermore, Jedi-1 and MEGF10
were identified as engulfment receptors on the membranes of SGC precursors involved in
this phagocytic process. Overexpression of Jedi-1 or MEGF10 in SGC precursors increased
the engulfment of apoptotic neurons, whereas knock-down of Jedi-1 or MEGF10 decreased
engulfment. The signaling pathways activated by Jedi-1 and MEGF10 are currently
unknown. However, Jedi-1 and MEGF10 are homologous to the engulfment receptor Draper
in Drosophila, which is phosphorylated by Src42A then bound by Shark. Draper and
another homolog in C. elegans, Ced-1, also interact with a phosphotyrosine (PTB) domaincontaining adapter protein, Gulp/Ced-6, and all of these interactions are necessary for
phagocytosis. We found that Src and Lck can phosphorylate Jedi-1 and MEGF10 on their
intracellular NPXY and ITAM motifs, respectively. We also found that Jedi-1 interacts with
both Gulp and Syk, a mammalian homolog of Shark, by co-immunoprecipitation, and the
interaction of Jedi and Syk is promoted by Lck overexpression. We are currently
investigating the role of Src Family Kinases, Syk, and Gulp in the engulfment of apoptotic
neurons.
Keywords: engulfment, Jedi-1, MEGF10, Gulp
62. KCNV2 (Kv8.2) Influences Epilepsy Susceptibility in Mice
and Humans
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Benjamin Jorge, Graduate Student
Authors: Benjamin Jorge, Courtney Campbell, Alison Miller, Elizabeth Rutter,
Christina Gurnett, Carlos Vanoye, Alfred George, Jr., M.D., Jennifer Kearney, Ph.D.
Lab P.I. or Faculty Mentor: Alfred George, Jr., M.D.
Department or Program: Neuroscience Graduate Program
A number of genes responsible for monogenic epilepsy have been identified in the last 15 years. Most
of the responsible genes are components of neuronal signaling, including voltage-gated sodium and
potassium channels. Mutations in the voltage-gated sodium channels SCN1A and SCN2A are
responsible for several types of human epilepsy. Variable expressivity among family members is a
common feature of these inherited epilepsies, suggesting that genetic modifiers influence clinical
severity. The mouse model Scn2aQ54 has an epilepsy phenotype caused by a mutation in Scn2a that
results in persistent sodium current. Clinical severity of the Scn2aQ54 phenotype is influenced by
genetic background, with a more severe phenotype on a (B6xSJL)F1 background compared to the B6
strain. This indicates that SJL carries dominant modifier alleles that influence severity of the epilepsy
phenotype. We previously mapped two modifier loci that influence epilepsy severity in Scn2aQ54
mice: Moe 1 on Chromosome 11 and Moe2 on Chromosome 19 (Bergren et al, Mamm Genome 16:683,
2005). Candidate gene analysis identified Kcnv2 as a potential modifier gene at the Moe2 locus
(Bergren et al, Mamm Genome, 20:359, 2009). Kcnv2 encodes the voltage-gated potassium channel
subunit Kv8.2 which forms heterotetramers with Kv2 family members. Kv8.2 influences membrane
translocation and channel properties of Kv2 channels which play an important role in controlling
membrane excitability.
Non-synonymous SNPs in Kcnv2 result in two amino acid differences between strains B6 (resistant)
and SJL (susceptible). In addition, strain SJL has a 3.5 fold increased expression of Kcnv2 transcript
in hippocampus compared to B6. In order to evaluate Kcnv2 as a modifier, we generated transgenic
mice expressing Kcnv2 with either the SJL or B6 sequence. For each version we generated multiple
lines expressing varying levels of transgene transcript. Kcnv2 transgenic mice were crossed with
Scn2aQ54 and offspring were phenotyped for spontaneous seizures. The level of Kcnv2 transgene
expression correlated with Scn2aQ54 seizure incidence and survival, regardless of whether the
transgene contained B6 or SJL sequence. This suggests that strain differences in Kcnv2 expression
levels may underlie the modifier effect. Increased expression of Kcnv2, which suppresses Kv2mediated delayed-rectifier potassium current, would be predicted to increase neuronal excitability
under conditions of repetitive stimulation.
To determine if KCNV2 plays a role in human epilepsy, we screened patient DNAs for variants in
KCNV2. We identified novel non-synonymous variants in two unrelated patients. Functional testing
of these variants in a heterologous expression system revealed greater suppression of Kv2.1-mediated
currents compared to wildtype KCNV2. This would be predicted to increase neuronal excitability,
suggesting a potential mechanism for seizure susceptibility.
Our results support a role for KCNV2 in epilepsy and demonstrate that isolation of genetic modifiers
in mice can lead to discovery of human epilepsy genes. Identification of genes that influence
susceptibility and disease progression will provide insight into the molecular events of
epileptogenesis, and may identify novel therapeutic targets for improved treatment of human
patients.
Keywords: epilepsy, Kv 82, Kcnv2
63. Young Children’s Attitudes Toward Their Peers Who Wear
Hearing Aids
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Lindsey Rentmeester, Graduate Student
Authors: Lindsey Rentmeester, Anne Marie Tharpe, Ph.D.
Lab P.I. or Faculty Mentor: Anne Marie Tharpe, Ph.D.
Department or Program: Hearing and Speech Sciences
The “hearing aid effect” is a phenomenon that describes negative attitudes toward children
wearing hearing aids when compared to their normal hearing peers. The hearing aid effect
has been found in adult observers and child observers as young as 10 years of age. The
purpose of this study was to determine whether the hearing aid effect is present in young
children and if there is a difference between the attitudes of young children (aged 6-7 years)
and older children (aged 9-10 years). Children with normal hearing were asked to rate
photos of their peers with a hearing aid and without a hearing aid in social acceptance, and
physical and cognitive competence. The findings from this study suggest that when directly
compared to their peers without hearing aids, children who wear hearing aids are more
likely to be viewed as being less capable physically and may be less socially accepted by their
peers.
Supported by the NIH National Institute on Deafness and Other Communication Disorders
(NIDCD) Short Term Research Traineeship (T35)
Keywords: hearing aids, attitudes, social development, hearing loss
64. Larger Amygdala and Hippocampus Volume as a
Biological Marker for Inhibited Temperament
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: April Seay, Graduate Student
Authors: April Seay, Jennifer Blackford, Ph.D.
Lab P.I. or Faculty Mentor: Jennifer Blackford, Ph.D.
Department or Program: Psychiatry
Background: Temperament refers to biologically-based differences in mood, emotions,
and behavior. One dimension of temperament is how a person responds to new and
unfamiliar situations. Inhibited individuals avoid novelty whereas uninhibited individuals
typically approach novelty. Inhibited and uninhibited are the two extremes that describe
approach to novelty. Inhibited temperament is a risk factor for anxiety disorders, and the
amygdala has been implicated as an important neural substrate. Using functional magnetic
resonance imaging (fMRI), previous studies have shown differences in amygdala function
between inhibited and uninhibited individuals. The purpose of this study was to explore
whether structural differences underlie the observed functional differences.
Methods: Seventy individuals (ages 18-40 years) with either extreme inhibited (n=36) or
uninhibited (n=34) temperament both as children and adults participated in the study.
Structural MRI images were collected on a 3T scanner. To assess volume, the amygdala and
hippocampus were manually segmented following standardized protocols. Temperament
group differences in amygdala and hippocampus volume were tested using analysis of
variance with age, gender, handedness, and race as covariates.
Results: In individuals with an inhibited temperament, the left amygdala and left posterior
hippocampus were significantly larger than in individuals with an uninhibited temperament.
Conclusion: This study demonstrates there are structural differences in the amygdala and
hippocampus between inhibited and uninhibited individuals. This study provides initial
evidence for a structural basis to the previously observed functional amygdala differences in
individuals with an inhibited temperament. Increased amygdala volume may contribute to
the higher incidence of anxiety disorders seen in inhibited temperament, and these
differences could correlate to risk factors for anxiety.
Keywords: inhibited temperament, amygdala , volumetry , hippocampus, segmentation
65. Parenting Stress, Coping, and Health: A Comparison Study
Across Disability Groups
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Nathan Dankner, Graduate Student
Authors: Nathan Dankner, Nancy Miodrag, Ph.D., Elisabeth Dykens, Ph.D.
Lab P.I. or Faculty Mentor: Elisabeth Dykens, Ph.D.
Department or Program: Vanderbilt Kennedy Center
Introduction: Parents of children with intellectual and developmental disabilities
experience high levels of stress. Variation across different disorders leads to unique
behavioral phenotypes, but at the same time, different disorders show high similarity to one
other. Given these similarities and differences, are maternal responses generalized or
disability-specific? Maternal psychological stress, coping, physical health, depressive
symptoms, and positive views on life and parenting have yet to be examined in the context of
multiple disorders.
Method: Data from 306 mothers of offspring with WS (n = 109), Prader-Willi syndrome
(PWS; n = 107); Down syndrome (DS; n = 19); and Autism Spectrum Disorders (ASD; n =
71) were drawn from a larger longitudinal study. Mothers and offspring ranged in age from
23-79 (M = 44.51) and 2-48 (M = 13.96), respectively. Mothers completed a battery of
questionnaires assessing stress, coping, physical and mental health, and positive life and
parenting.
Results: A series of MANCOVAs controlling for demographics were conducted to determine
the effect of the four child diagnostic groups on the testing battery. There were no significant
differences among the four groups on coping and depressive symptoms. There was a trend
for significant differences among the groups for both health problems and positive life and
parenting.
Significant group differences were found on psychological stress. ANCOVAs on the stress
variables produced significant group differences for each subscale: parental distress, parentchild dysfunctional interaction, difficult child, total stress, and life stress. Post hoc analyses
revealed significant differences between mothers of children with WS and ASD as well as WS
and PWS with the former reporting less distress, parent-child problems, difficult child
behaviors, overall stress, and fewer life stressors.
Discussion: The findings suggest differential stress effects for mothers of children with WS
compared to mothers of children with other disability groups, in that raising a child with WS
is perceived as less stressful. Other maternal responses (e.g., coping or depression) are not
differentiated by child diagnosis. The data indicate that raising a child with ASD or PWS can
be particularly stressful, while mothers of children with WS may benefit from protective
factors associated with the disorder.
Keywords: stress, parent health, Williams syndrome, Prader-Willi syndrome, autism spectrum
disorders
66. Neurobiological Correlates of Sentence Comprehension in
Adolescent Struggling Readers
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Laura Barquero, Graduate Student
Authors: Laura Barquero, Aanandhi Venkatadri, Lindsay Wilson, Nicole Davis,
Ph.D., Sheryl Rimrodt, M.D., Laurie Cutting, Ph.D.
Lab P.I. or Faculty Mentor: Sheryl Rimrodt, M.D., Laurie Cutting, Ph.D.
Department or Program: Pediatrics, Special Education
Purpose: We examined the neurobiological correlates of sentence comprehension (SC) and
single word reading (WR) in participants with reading disabilities and control participants.
Though previous work has explored differences in sentence and word-reading activations,
this study further expanded upon previous work by examining sentences (without
comparison to words), as well as isolated words themselves.
Method: Adolescents with reading disabilities (n=9) and control participants (n=8)
performed two in-magnet reading tasks in a block design. One task involved reading single
high frequency words visually presented on a screen. The second task differed in that
sentences were presented. Participants determined whether the words were real or not and
whether sentences were meaningful or not and responded by button presses. BOLD
response indicated activation. Whole-brain t-contrasts were performed for condition and
group contrasts.
Results: Contrast maps for SC-WR showed greater activation for participants with RD in
the LH insula. Individual contrasts with sentences and words versus fixation also revealed
differences between groups, particularly in traditionally seen areas (e.g., RD showed lower
activation in occipito-temporal areas as compared to controls for both SC and WR).
Conclusions: Results from the SC-WR contrasts replicate findings from an earlier study
(Rimrodt et al., 2009) in showing increased LH superior frontal gyrus activation in controls
and increased LH insula activation in RD. In addition to these findings, the exploration of
sentences as well as words as compared to baseline fixation may reveal further aspects of
differences in the neural correlates of higher level comprehension in adolescents with RD.
Keywords: reading, fMRI, sentence comprehension
67. Altered White Matter Integrity in Prefrontal-Amygdala
Pathways in Williams Syndrome
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Suzanne Avery, Graduate Student
Authors: Suzanne Avery, Tricia Thornton-Wells, Ph.D., Jennifer Blackford, Ph.D.
Lab P.I. or Faculty Mentor: Tricia Thornton-Wells, Ph.D., Jennifer Blackford, Ph.D.
Department or Program: Psychiatry
Williams Syndrome (WS) is a rare neurodevelopmental disorder caused by a hemizygous
microdeletion on chromosome 7q11.23. Individuals with WS are engaging and socially
disinhibited, but surprisingly have significant nonsocial fears. Consistent with this elevated
nonsocial fear, individuals with WS show an abnormally increased amygdala blood oxygen
level dependent (BOLD) response to fearful nonsocial stimuli. Amygdala activity is
modulated through dense reciprocal white matter connections with the prefrontal cortex
(PFC). Individuals with WS show abnormal BOLD activity in the PFC while viewing fearful
nonsocial images, suggesting that a functional uncoupling of normal PFC-amygdala
modulation may underlie the extreme amygdala activity and nonsocial fears observed in WS.
It is unknown if this modulatory signaling deficit in WS is a result of aberrant structural
connectivity in PFC-amygdala pathways. We used diffusion tensor imaging (DTI) to
investigate potential PFC-amygdala white matter integrity differences in WS. We recruited 8
individuals with WS and 9 controls. We used a control group of individuals who were
typically developing but demonstrated high rates of nonsocial fear. Probabilistic
tractography was used to isolate PFC-amygdala white matter pathways in each individual.
Within each tractography pathway, we examined two diffusion measures for potential
between-group differences: fractional anisotropy (FA) and radial diffusivity (RD). FA is a
general measure of white matter integrity, while RD, a component of FA, is a more specific
measure of fiber coherence and myelination. White matter diffusion was significantly
altered in WS compared to controls in several PFC-amygdala modulatory pathways. WS
individuals showed decreased FA compared to controls, which indicates a general loss of
white matter integrity in WS. To further investigate this FA difference, we tested for
between-group differences in RD values. RD was significantly increased in WS compared to
controls, suggestive of decreased fiber coherence or axon myelination in PFC-amygdala
paths. These results suggest that deficits in the structural integrity and coherence of PFCamygdala pathways may underlie the extreme nonsocial fears observed in WS.
Keywords: Williams syndrome, amygdala, prefrontal cortex, diffusion tensor imaging
68. Open board
69. GTF2IRD1: Temperamental, or Not? Copy Number
Variation in WS and Controls
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Alison Wright, Graduate Student
Authors: Alison Wright, Jennifer Blackford, Ph.D., Tricia Thornton-Wells, Ph.D.
Lab P.I. or Faculty Mentor: Jennifer Blackford, Ph.D., Tricia Thornton-Wells, Ph.D.
Department or Program: Center for Human Genetics Research
Williams Syndrome (WS) is a rare genetic disorder caused by the hemizygous microdeletion
of approximately 25 genes on chromosome 7q11.23. In persons with WS, hypersociability, a
lack of social inhibition, and a very empathetic nature coexist with non-social fears and
anxiety. However, in the general population, social inhibition and non-social anxiety often
go hand-in-hand. GTF2IRD1, a gene within the WS deletion region, has been hypothesized
to have a direct and independent affect on sociability and anxiety in Williams Syndrome
patients. It was shown by Young, et al. (2008) that mice heterozygous or homozygous for
Gtf2ird1 exhibit lower fear and aggression but increased social interaction reminiscent of
traits in WS patients. In this study, we compared individuals with WS to two novel typicallydeveloping control groups—persons with inhibited (IT) who are shy and have elevated rates
of anxiety, and persons with uninhibited temperament (UT), who are outgoing and have low
rates of anxiety. We analyzed three high-quality copy number variant (CNV) markers within
GFT2IRD1. All but one WS subject had the expected 1 copy for each marker. However,
unexpectedly, 3 persons with IT and 6 persons with UT also had 1 copy of each of the 3
markers. This is the first report of CNVs in GTF2IRD1 in typically developing individuals,
and is an important finding that might aid in the interpretation of genotype-to-phenotype
mappings in WS. Palmer et al. (2010) have shown that Gtf2ird1 is autoregulated in mice and
that transcript levels of GTF2IRD1 in WS-patient-derived cell lines exhibit dosage
compensation. If this mechanism is similar in vivo, one might expect that isolated CNVs
involving this gene would have only a subtle phenotypic effect and that, from an
evolutionary genetics standpoint, that such variants would not undergo selection. We are in
the process of obtaining CNV data from an existing cohort of typically developing individuals
to estimate the frequency of such copy number variants in the general population.
Keywords: Williams syndrome, temperament, anxiety, copy number variation
70. Coping and Regulation of Positive Affect in Children with
Cancer
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Madeleine Dunn, Graduate Student
Authors: Madeleine Dunn, Erin Rodriguez, Teddi Zuckerman, Kelly Haker, Julie
Grossenbacher, Kimberly Miller, Kathryn Vannatta, Cynthia Gerhardt, Bruce
Compas, Ph.D.
Lab P.I. or Faculty Mentor: Bruce Compas, Ph.D.
Department or Program: Psychology and Human Development
Previous research suggests that the ways that children cope with cancer may contribute to
resilience for some children (Aldridge & Roesch, 2007). Resilience has been conceptualized
as the ability to maintain positive affect in the face of adversity (Davidson, 2000). The
current study examined how children’s coping strategies with regard to their cancer were
associated with resilience (observed positive affect) and negative affect (observed sadness).
Twenty-five children diagnosed with cancer and on active treatment, ages 10 to 17 (M = 13.1,
SD = 2.6), completed the Responses to Stress Questionnaire (Connor-Smith et al., 2000)
and the Youth Self-Report (YSR; Achenbach et al., 2001). The RSQ measures self-reported
coping strategies: primary control coping (PCC; e.g. emotional expression), secondary
control coping (SCC; e.g. acceptance), and disengagement (DIS; e.g. avoidance). The
Affective (AFF) and Anxiety (ANX) Problems scales of the YSR measure psychological
adjustment. Children were rated on positive affect (PA) and sadness (SD) during a 15-minute
recorded conversation with their mother about their cancer using the Iowa Family
Interaction Rating Scales (Melby & Conger, 2001). Children’s reports of coping were related
to their adjustment: PCC was related to lower ANX symptoms (r = -.42, p < .05); SCC to
lower AFF and ANX symptoms (r’s = -.50, -.67, p < .05, respectively); DIS to more ANX
symptoms (r = .52, p < .05). Children’s observed SD (M = 5.5, SD = 1.32) was not related to
reports of coping (ns). Observed PA (M = 5.4, SD = 1.67) was related to PCC (r = .47, p <
.05), SCC (r = .39, p < .05), and DIS (r = -.42, p < .05). Observed levels of PA were related to
lower AFF (r = -.42, p < .05). These findings add to previous work that PCC and SCC have
been related to better psychological adjustment in children and DIS to poorer adjustment
(e.g., Jaser et al., 2005). In addition, this work supports the idea that more adaptive coping
strategies are associated with resilience (positive affect) during a stressful conversation
(Davidson, 2000). Overall, these findings suggest the potential importance of teaching
specific coping strategies to children with cancer in order to increase PA and relieve
psychological distress.
Keywords: coping, cancer, resilience, positive affect
71. Asymmetry of the Face Processing Region of the Neocortex
Distinguishes Homo sapiens from Chimpanzees
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Eva Sawyer, Graduate Student
Authors: Steven Chance, Eva Sawyer, Linda Clover, Bridget Wicinski, Patrick Hof,
Timothy Crow
Department or Program: Neuroscience Graduate Program
Humans show a propensity to use their right fusiform gyrus when processing faces and their
left when processing written words. Leftward functional asymmetries are also found when
humans listen and speak. Functional language asymmetry have been linked to anatomical
brain asymmetries found only in humans, such as wider connective spacing between the
minicolumns of neurons in the left planum temporale, an auditory association area, than in
that area on the right. We tested the principle that minicolumn asymmetry should follow the
direction of language dominance, and tested the human uniqueness of such asymmetric
architecture by measuring minicolumn width, neuronal size and density in fusiform face
cortex in humans and chimpanzees. We found a human-specific leftward microanatomical
asymmetry matching the skew seen in language areas. Human minicolumns are therefore
expanded in the hemisphere dominant for language, a novel function, whereas minicolumns
are narrow in the hemisphere dominant for face processing, an evolutionarily conserved
function. Our findings are consistent with the mechanistic hypothesis of minicolumn
organization that proposes that wider minicolumns facilitate featural processing (suitable
for language dominance) whereas narrow minicolumns facilitate holistic processing
(suitable for faces). These results may show an anatomical basis for lateralization of
communication in the human fusiform.
Keywords: cerebral asymmetry, minicolumn, face processing, chimpanzee
72. Children of Depressed Parents Are at Increased Risk for
Depression
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Claire Borgschulte, Undergraduate Student
Authors: Claire Borgschulte, Sarah Frankel, Judy Garber, Ph.D.
Lab P.I. or Faculty Mentor: Judy Garber, Ph.D.
Department or Program: Psychology and Human Development
Children of depressed parents are at increased risk for depression themselves. The current
study examined whether the relation between risk (i.e., having a parent with depression) and
children’s depressive symptoms (Children’s Depression Inventory) varied as a function of
children’s age, sex, pubertal status (Pubertal Development Scale), and parent-child conflict
(Conflict Behavior Questionnaire). Participants were 227 parent-child dyads; 129 parents
were in treatment for depression (high-risk) and 98 parents were lifetime-free of
psychopathology (low-risk). Linear regression analyses revealed that high-risk children
reported significantly higher levels of depressive symptoms than low-risk children. There
was a nonsignificant trend for the relation between risk and children’s depressive symptoms
to be moderated by child sex. The parent-child depression relation did not differ as a
function of children’s age, but was moderated by pubertal development. The relation
between risk and children’s depressive symptoms also was moderated by parent-child
conflict. Thus, children of depressed parents who are more pubertally developed or report
more parent-child conflict may be at greater risk for depression and therefore should be
targeted for intervention.
Keywords: depression, gender, families
73. The Serotonergic and Somatosensory Systems in
Serotonin Transporter Ala56 Knockin Mice
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Chris Muller, Graduate Student
Authors: Chris Muller, A. Bonnin, J. Sauer, T. Kerr, P. Levitt, James Sutcliffe, Ph.D.,
Randy Blakely, Ph.D., Jeremy VeenstraVanderWeele, M.D.
Lab P.I. or Faculty Mentor: James Sutcliffe, Ph.D., Randy Blakely, Ph.D., Jeremy
Veenstra-VanderWeele, M.D.
Department or Program: Center for Molecular Neuroscience
Elevated whole blood serotonin (5-HT) levels are present in approximately a quarter of
individuals with autism spectrum disorders (ASD). In addition, there is robust evidence of
genetic linkage with ASD in the 17q11 region that contains SLC6A4, the gene encoding the
serotonin transporter. A rare serotonin transporter (SERT) coding variant, Gly56Ala, that
causes elevated 5-HT transport, is associated with sensory aversion and rigid-compulsive
behaviors in male ASD probands. We have developed mice that express the SERT Ala56
variant to characterize its effect on behavior and brain development. The Ala56 mice exhibit
increased clearance of 5-HT in the hippocampus in vivo. Initial behavioral studies in the
Ala56 mice demonstrate abnormal social and sensory phenotypes. The mutant mice exhibit
reduced dominance in the tube test. The Ala56 mice also exhibit decreased pre-pulse
inhibition. Ongoing studies are examining other sensory phenotypes and repetitive behavior
in the Ala56 variant mice. Furthermore, pharmacological manipulation of the serotonergic
system revealed both presynaptic and postsynaptic receptor hypersensitivity in the Ala56
mice. Current work is focusing on the Ala56 variant’s effect on brain cytoarchitecture and
development. Several studies have implicated the serotonergic system in the formation of
mouse barrel field architecture in primary somatosensory cortex. 5-HT also influences
thalamo-cortical axon guidance via 5-HT1B/1D receptor modulation of netrin-1 (Bonnin et
al. 2007). We are evaluating the impact of the Ala56 variant’s effect on barrel cortex
architecture with cytochrome oxidase staining. We are also using Netrin-G1a
immunostaining of E18.5 embryos to characterize the Ala56 variant’s effect on thalamocortical axon pathfinding during development. Our studies to date reveal multiple
physiological, pharmacological and behavioral phenotypes in the SERT Ala56 mice that
provide insights into the role of the serotonergic system in ASD.
Keywords: autism spectrum disorders, serotonin transporter, serotonin, animal models, sensory
74. Regional Brain Atrophy Measurements Are Associated
with Gene-Gene Interaction Models in Alzheimer Disease
Neuroimaging Initiative (ADNI)
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Nicole Restrepo, Graduate Student
Authors: Nicole Restrepo, Tricia Thornton-Wells, Ph.D.
Lab P.I. or Faculty Mentor: Tricia Thornton-Wells, Ph.D.
Department or Program: Chemical and Physical Biology Program
Alzheimer’s disease (AD) is the most prevalent form of dementia and currently affects more
than 4 million Americans. Current treatments for patients are limited and often ineffective
by the time a patient is clinically diagnosed. Early biomarker research aims to shorten the
time between disease development and diagnosis in an attempt to medically intervene when
damage is minimal. Neuroimaging methods have the ability to detect and quantify early,
preclinical changes in brain structure and function. These neuroimaging measures can also
be used as intermediate phenotypes in genetic association studies, to address clinical and
genetic heterogeneity that exists in this common, complex disease. Numerous studies have
shown an association between AD and MRI measures of regional brain atrophy, particularly
in the hippocampus and entorhinal cortex (Risacher SL et al., 2009). More recently,
genome-wide association studies of AD have reported single SNP associations with MRI
measures of hippocampal and entorhinal cortex atrophy (Potkin SG et al., 2009; Furney SJ
et al., 2010). We aimed to test for association with gene-gene interactions, which might more
closely model the complex genetic architecture of AD. We utilized a two-stage bioinformatics
and imaging genetics approach. We first used Biofilter software to mine existing databases
(e.g., KEGG, GO, Pfam, etc.) for biological evidence regarding which genes are likely to
interact and to be associated with AD. We then tested a prioritized set of 4814 SNP-SNP
interactions for association in the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
dataset, which contained approximately 200 elderly controls, 400 subjects with mild
cognitive impairment, and 200 patients with mild AD. Annual rate of atrophy was
determined for the hippocampus, parahippocampal gyrus, and the entorhinal cortex using
structural MRI data. Linear regression was used to test how well the selected SNP-SNP
interaction models could predict these quantitative MRI atrophy measures. There were 46
unique models with a significance of p≤0.01. Top models suggest a possible correlation
between atrophy and the Hexokinase family of proteins. A top snp-snp model associated
with hippocampal atrophy identifies hexokinase IV (glucokinase) as a risk factor. This
enzyme plays a major role in glycolysis, with implications in Alzheimer’s and diabetes.
Keywords: Alzheimer’s disease, linear regression, epistasis, neuroimaging, brain atrophy
75. To Be or Tonotopy: Implications of Tonotopic
Representation in the Mouse Auditory Thalamus
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Barbara O’Brien, Graduate Student
Authors: Barbara O’Brien, Troy Hackett, Ph.D., Vivek Khatri, Michelle Howell
Young, Zachary Barnett, Daniel Polley, Ph.D.
Lab P.I. or Faculty Mentor: Troy Hackett, Ph.D.
Department or Program: Neuroscience Graduate Program
The ear is constantly sampling auditory stimuli in the environment, and the role of the
central auditory system is to take auditory cues presented to the ear and decipher meaning
such as where the signals come from and what they are. One property of auditory stimuli
that the auditory system codes for is frequency. Tonotopy is the topographic representation
of frequencies to which neurons give an optimal response and is the most-studied
characteristic of auditory stimulation. While the tonotopy of other subcortical structures has
been well described, the physiology of the auditory thalamic nucleus, the medial geniculate
body (MGB), has not been explored in depth. Here, we investigated the tonotopic
organization of the ventral division of the medial genciculate body (MGBv), which
constitutes the main input to the primary auditory cortex area 1 (A1). We presented pure
tone pips (4 kHz to 40 kHz) to the contralateral ear of anesthetized mice while recording
multiunit activity on a sixteen-channel multi-electrode array in the MGBv. We also recorded
multi-unit activity in the middle layers of A1 to establish a tonotopic map based on bestfrequency (BF), the frequency to which cells respond at minimum intensity. Two retrograde
tracers of cholera toxin subunit B (CTB) (conjugated to either fluorescent green or
fluorescent red) were injected into the low- and high-frequency representations of A1 in
order to address if topographic representation in A1 arose from topographic projections
from MGBv. Electrophysiological recordings in the MGBv showed a progression of BF-shift
from low-to-high in a caudolateral-to-rostromedial organization. Supporting this
physiological shift, injections patterns identified separation in neuronal labeling in a similar
manner, confirming a caudolateral-to-rostromedial organization of the MGBv and its
projections to A1. Our findings indicate that mouse MGBv possesses a tonotopic organized
that is preserved in its projections to A1.
Keywords: auditory, tonotopy, medial geniculate body
76. Examining a Potential Gene-Environment Interaction
Between the PD-Associated Gene Parkin and Manganese in a
C. elegans Model
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Sudipta Chakraborty, Graduate Student
Authors: Sudipta Chakraborty, Michael Aschner, Ph.D.
Lab P.I. or Faculty Mentor: Michael Aschner, Ph.D.
Department or Program: Neuroscience Graduate Program
The heavy metal manganese (Mn) is a trace element that serves as an imperative
micronutrient in our diet. However, environmental overexposure can lead to a toxic
condition known as manganism. This disorder shares similar neuropathology with
Parkinson's disease (PD), implicating dopaminergic (DAergic) cells of the substantia nigra
(SN) as the primary target of death. Both manganism and PD lead to neurological and motor
deficits, along with increased mitochondrial dysfunction. The mechanisms behind these
disorders, however, are still unknown. Of recent interest are methods to elucidate a potential
gene-environment interaction, using C. elegans as a genetic model that contains the
necessary DAergic machinery. Many genes associated with PD have been identified in the
literature, including the parkin/PARK2 (pdr-1 in worms) gene that encodes for an E3ubiquitin ligase protein that is also involved in inducing autophagy of damaged
mitochondria (mitophagy). It has been previously shown that Mn toxicity exhibits specificity
to DAergic cells, and that parkin confers protection to these cells from Mn exposure in vitro.
We, therefore, hypothesized that a loss-of-function mutation in parkin increases the
vulnerability of C. elegans to Mn toxicity. Synchronous L1 worms from wildtype N2 and pdr1 mutant strains were acutely treated with a range of Mn doses (0-1000 mM MnCl2) for 30
minutes, followed by lethality scoring of approximately 200 worms 24 hours after treatment.
Using transgenic worms containing a pdr-1 deletion, we show that a loss in parkin increases
vulnerability to Mn toxicity (LD50=33.64 mM MnCl2) compared to wild-type N2 worms
(LD50=59.27 mM MnCl2), seen with a leftward shift in the dose-response curve. This data
indicate that parkin is protective against Mn toxicity in vivo, with loss of parkin potentially
producing increased oxidative stress from impaired mitophagy.
Keywords: manganism, parkin, neurodegenerative disease, neurotoxicity, metal transport
77. Sensory Modulation in Williams Syndrome
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Jennifer Pryweller, Graduate Student
Authors: Jennifer Pryweller, M. Choo, Elisabeth Dykens, Ph.D., Carissa Cascio,
Ph.D., Tricia Thornton-Wells, Ph.D.
Lab P.I. or Faculty Mentor: Elisabeth Dykens, Ph.D., Tricia Thornton-Wells, Ph.D.
Department or Program: Interdisciplinary Studies, Neuroimaging of
Neurodevelopmental Disorders
Sensory modulation involves filtering and gating of multiple sensory inputs and is essential
for efficient processing of sensory signals. Regulation of neural messages in a graded and
adaptive manner is given by facilitation or inhibition of responses to sensory input, allowing
isolation of relevant or salient information from the array of sensations experienced. Sensory
modulation gives meaning to an individual’s sensory experiences related to the environment
or from within his or her own body and is imperative to day-to-day functioning, learning and
social behavior. Impairments in sensory modulation are often reflected in individuals as
difficult temperaments, problem behaviors, inattention, difficulty regulating arousal levels,
and trouble establishing relationships.
The Sensory Profile Caregiver Version (SP; Dunn, 1999) is a 125 item parent report that
measures sensory processing abilities and profiles the effect of sensory modulation
differences on functional performance in the daily life of an individual. Reported frequencies
of itemized behaviors are scored along a 5-point Likert scale, yielding raw scores and
classification categories for both a total score and nine scales that characterize individuals by
their responsiveness to sensory input.
Williams Syndrome (WS) is a rare genetic disorder caused by the deletion of ~26 genes on
chromosome 7q11.23 and is characterized by mild to moderate intellectual disability,
visuospatial deficits, congenital heart defects and dysmorphic facial features. The personality
profile of individuals with WS includes socially-expressive language, heightened empathy
and facial processing abilities, auditory fetishes (aversive and attractive), non-social anxiety
and fears, and a strong musical interest and/or ability.
Atypical sensory modulation has been described in multiple neurodevelopmental disorders,
including ADHD, Autism, Angelman Syndrome and Fragile X Syndrome. We aimed to
characterize sensory modulation in WS. Caregivers of 37 individuals with WS aged 3.5 – 49
years (age [meanSD]: 13.410.6; 18 females, 19 males) completed the SP at the 2010
Williams Syndrome National Convention. Data entry is complete and analyses are ongoing
to characterize sensory modalities in William’s Syndrome that have not been explored
previously. These results will be compared to published data from typically developing
individuals as well as individuals with ADHD and Autism.
Keywords: Williams syndrome, sensory modulation
78. The Role of p75NTR Cleavage During the Developmental
Apoptosis of Sympathetic Neurons in vivo
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Bradley Kraemer, Graduate Student
Authors: Bradley Kraemer, Rajappa Kenchappa, Jami Scheib, Bret Mobley, Bruce
Carter, Ph.D.
Lab P.I. or Faculty Mentor: Bruce Carter, Ph.D.
Department or Program: Neuroscience Graduate Program, Biochemistry
Within the vertebrate nervous system, the p75 neurotrophin receptor (p75NTR) has
numerous functional roles, including regulating neurite outgrowth, myelin formation, and
cell survival. In developing superior cervical ganglia, activation of p75NTR by BDNF or proBDNF produces an apoptotic signal. We have previously shown in cultured sympathetic
neurons that p75NTR is cleaved by gamma-secretase in response to pro-apoptotic ligands,
and this proteolysis was required for the subsequent ubiquitination and nuclear
translocation of the transcription factor NRIF. Inhibition of p75NTR cleavage by a γsecretase inhibitor or by expression of a mutant, noncleavable form of the receptor
(p75FasTM) stopped the nuclear translocation of NRIF and prevented programmed cell
death. In the present study, we investigated the role of these signaling events in vivo using
transgenic mice expressing p75FasTM under the control of the neuronal promoter Tα1tubulin. Sympathetic neurons of early postnatal p75FasTM mice have reduced p75NTR
cleavage in vivo and are resistant to BDNF-induced cell death in culture. We are currently
assessing how p75FasTM expression affects the developmental apoptosis of SCG neurons in
vivo. In addition, we are analyzing other aspects of p75NTR signaling, including NGFdependent cell survival signaling through its interaction with TrkA. The effects of p75FasTM
expression on p75NTR signaling in other regions of the nervous system are also being
investigated. This work will enhance our understanding of the signaling mechanisms
through which p75NTR regulates neuronal survival during the development of the
mammalian nervous system.
Keywords: p75, neurotrophin, gammasecretase, BDNF, NGF
79. Association of Tactile Symptoms with Core Features of
Autism: Evidence from Direct Observation and Parent Report
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Jennifer Foss-Feig, Graduate Student
Authors: Jennifer Foss-Feig, Jessica Heacock, Celina Jacobi, Cara Damiano, Jennifer
Pryweller, Alyson Hasty, Bradley Stirling, Margaret Choo, Carissa Cascio, Ph.D.
Lab P.I. or Faculty Mentor: Carissa Cascio, Ph.D.
Department or Program: Psychology and Human Development
Background: Differences in sensory processing have been noted in autism spectrum
disorders (ASD) across modalities, and sensory processing differences discriminate children
with ASD from those with both typical development (TD) and generalized intellectual
disability (ID). Evidence exists for both sensory seeking and defensiveness in ASD, and for
both hypo- and hyper-responsiveness to sensory input. Of note, at least one study found
that hyporesponsiveness best discriminated individuals with ASD from those with ID. While
visual and auditory processing have been the focus of many studies, less is known about
tactile processing and its relation to core symptomatology in ASD.
Methods: Tactile processing was examined in 33 children with ASD between 5 and 7 years
(mean CA=6.8 years, mean MA=5.2 years) using the Tactile Defensiveness and
Discrimination Test-Revised (TDDT-R). Parent report of tactile processing was collected
using the Sensory Profile (SP) and the Sensory Experiences Questionnaire (SEQ). ASD
symptomatology was assessed directly with the ADOS, and parent report was obtained from
the ADI-R. Correlations were conducted between measures of tactile processing and
assessments of social, communicative, and behavioral differences in ASD.
Results: Increased tactile seeking behaviors indexed on the TDDT-R and SEQ were
associated with increased social impairment on the ADOS and ADI-R and increased
repetitive behaviors on the ADOS. In contrast, increased tactile defensiveness on the
TDDT-R was associated with decreased repetitive behaviors on the ADOS. Greater tactile
hyporesponsiveness, measured by the SP, was related to increased social impairment on the
ADOS and ADI-R, increased nonverbal communication impairments on the ADI-R, and
increased repetitive behaviors on the ADOS. The SEQ tactile hyporesponsiveness index was
correlated with ADI-R report of increased social and non-verbal communication symptoms.
However, neither the SP or SEQ measures of tactile hyperresponsiveness were correlated
with any core ASD symptom domain.
Discussion: Results suggest that increased hyporesponsiveness to external tactile input as
well as increased internally-driven tactile seeking behavior are associated with increased
social-communicative impairment and higher levels of restricted and repetitive behaviors.
Tactile defensiveness and hyper-responsiveness, however, seem less related to core ASD
symptoms. Future research exploring the neural mechanisms underlying these relations is
warranted.
Keywords: autism spectrum disorders, sensory, tactile, assessment
80. Binge Cocaine Administration in Adolescent Rats Affects
Amygdala Gene Expression Patterns and Alters AnxietyRelated Behavior in Adulthood
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Stephanie Bronson, Graduate Student
Authors: Stephanie Bronson, Y. Black, A. Naydenov, F. Vassoler, R. Hanlin, Christine
Konradi, Ph.D.
Lab P.I. or Faculty Mentor: Christine Konradi, Ph.D.
Department or Program: Neuroscience Graduate Program
Cocaine is a psychostimulant drug that has long lasting behavioral and neurobiological
consequences. Administration of cocaine during adolescent periods has been shown to affect
neurotransmission, synaptic development, and behavioral sensitization. In previous studies
we reported that binge cocaine administration in rodents during adolescence produces
deficits in prefrontal cortex (PFC)-mediated behavior and alters gene expression patterns of
cell adhesion molecules and transcription factors (Black 2006). In addition to attentional
processing and executive functioning, the PFC relays information to the amygdala about
fear-provoking stimuli and participates in the acquisition of fear memories. The goal of the
present study is to understand the molecular and behavioral effects in the amygdala that
arise from binge cocaine administration in adolescent rodents. Adolescent male Sprague
Dawley rats (P35) were injected intraperitoneally three times daily with either 0.9% saline or
cocaine HCl in an ascending binge paradigm that corresponds to human adolescent drug use
observed in teenagers. On P70, rats were evaluated for anxiety-related behaviors using open
field, elevated plus maze, and conditioned freezing tests. Rats injected with cocaine during
adolescence display less anxiety when placed in an open field chamber, and spend
significantly more time in the center of the chamber. Since healthy levels of anxiety mediate
cautious behavior in novel or dangerous situations, our data indicate that cocaine treatment
causes the animals to be less cautious and more “risk-taking” during adulthood. In a gene
expression microarray analysis of the amygdala from a subset of animals that were sacrificed
22 hours after the last injection, we detected significant changes in components of the Wnt
signaling pathway, including GSK 3-beta, TGF 3-beta, beta catenin, cadherin, and integrin
beta-6. This signaling pathway is believed to be involved in the acquisition of fear memories,
suggesting that cocaine interferes with this process. The data show that cocaine exposure
during adolescence may affect the proper development of a circuitry that mediates anxiety
and normal fear responses in adulthood, leading to higher risk-taking and a deficit in normal
fear behavior.
Keywords: adolescents, binge, cocaine, anxiety, amygdala
81. Preschool Teacher Talk: How Much Complex Syntax is in
There?
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Jamie Fisher, Graduate Student
Authors: Jamie Fisher, Karen Barako Ardnt, Kathryn Guillot, Sandra Combs, C.
Melanie Schuele, Ph.D.
Lab P.I. or Faculty Mentor: Melanie Schuele, Ph.D.
Department or Program: Hearing and Speech Sciences
Teacher talk was examined during an art activity and dramatic play. The amount and types
of complex syntax were analyzed as well as the purpose for which teachers used complex
syntax. Complex syntax consisted mostly of infinitival complements used in the context of
directing children's activities. Clinical implications are discussed.
Keywords: complex syntax, teacher talk
82. Effect of Glucose Deprivation and Valproic Acid on
Mitochondrial DNA Copy Number in Psychiatric Illness
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Hayley Boyd Clay, Graduate Student
Authors: Hayley Boyd Clay, Alison Walden, Stephan Heckers, M.D., and Christine
Konradi, Ph.D.
Lab P.I. or Faculty Mentor: Stephan Heckers, M.D., Christine Konradi, Ph.D.
Department or Program: Psychiatry
Psychiatric illnesses are among the most common causes of disability, yet their disease
mechanisms are poorly understood. Recent data from our lab suggest that one particular
psychiatric illness, bipolar disorder (BPD), may involve mitochondrial abnormalities:
postmortem hippocampus samples from BPD patients exhibit reduced expression of
mitochondria-related genes, and lymphocytes from BPD patients failed to up regulate
mitochondria-related genes in response to glucose deprivation. To expand our analysis of
glucose-deprivation-induced changes in gene expression, we are culturing lymphocytes
derived from psychiatric patients and controls in normal- or low-glucose media for 5 days,
followed by RNA extraction and microarray analysis. In addition, we are investigating
whether alterations in mitochondria-related gene expression correlate with changes in the
levels of mitochondrial DNA (mtDNA). In this study, we subject lymphoblastoid cell lines to
the same glucose-deprivation paradigm used for the lymphocytes, followed by DNA
extraction and real-time quantitative PCR to assess mtDNA levels relative to nuclear DNA
levels. Since our initial lymphocyte study found mitochondria-related changes in BPD, we
are also exposing glucose-deprived lymphoblastoids to therapeutic concentrations of
valproic acid, a mood stabilizer commonly used to treat BPD, to investigate whether this
drug affects mtDNA copy number in a disease- or stress-dependent manner. Disease-related
abnormalities in mtDNA copy number regulation, whether at baseline or during cell stress,
could introduce a new facet to the understanding of the pathophysiology of psychiatric
disease, as well as further indicate that mitochondria-targeted drugs may serve as a
promising avenue for the treatment of mental illnesses.
Keywords: bipolar disorder, glucose, mitochondria
83. Effects of a Year of Kindergarten on Executive Functions
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Ayzit Doydum, Graduate Student
Authors: Ayzit Doydum, Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
Executive functions (EFs) encompass domain-general abilities to control one’s focus, think
flexibly, and resist distraction, and have been found to be one of the most important
predictors of subsequent academic success in elementary school children. Although
educational success is clearly linked to development of EFs in children, little research has
investigated the effect of education on EF development in school-aged children. This study
utilizes schools’ cut-off dates as a natural experiment that separates children of roughly the
same age into young Kindergarteners and old preschoolers and then tracks changes in
performance on EF tasks and math ability tests over the course of a school year. Use of the
school cut-off allows us to isolate and compare the effects of schooling and age.
Our EF tasks: (1) In the Flanker Task, a central target fish is flanked by fish on the left and
right that either point in the same direction (congruent) or opposite direction (incongruent)
compared to the target fish. (2) In the Rule-Switch Task, children are instructed that red fish
swim forwards and blue fish swim backwards. Each trial is either a switch trial (e.g., red fish
trial preceded by blue fish trial) or a non-switch trial (e.g., red fish trial preceded by red fish
trial). These tasks are administered along with math subtests from the Woodcock-Johnson
III Tests of Achievement.
We have currently tested 35 students at the beginning of their Kindergarten (n=17) or firstgrade year (n=18) to assess the effects of Kindergarten education. In the Flanker Task,
younger children have higher conflict scores on incongruent trials compared to congruent
trials (Fig 1). In the Rule-Switch Task, younger children have higher switch costs, indicating
the extra effort needed when switching rules between successive trials (switch) compared to
trials in which there is no rule switch (same) (Fig 2). The figures hint there may be an
interaction across these two tasks suggesting they measure different EF components.
Further data collection, comparison with math ability, and an assessment at the end of the
school year will provide us with a clear picture of how Kindergarten versus a first-grade
curriculum shapes EFs.
Keywords: executive function
84. Glucagon-Like Peptide-1 is a Novel Regulator of Striatal
Dopamine Homeostasis
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Kevin Erreger, Ph.D., Postdoctoral Fellow
Authors: Kevin Erreger, Ph.D., Adeola Davis, Sabrina Robertson, Erin Watt, Kelly
Rogers, Heinrich Matthies, C. Saunders, Roxanne Vaughan, Anthony West, Nigel
Greig, Kevin Niswender, M.D., Ph.D., Aurelio Galli, Ph.D.
Lab P.I. or Faculty Mentor: Aurelio Galli, Ph.D.
Department or Program: Molecular Physiology and Biophysics
Glucagon-like peptide-1 (GLP-1) is secreted from the gastrointestinal tract in response to
nutrient ingestion and regulates glucose homeostasis by increasing insulin release. GLP-1 is
known to decrease food intake by both peripheral and central mechanisms. While GLP-1
clearly contributes to homeostatic regulation of food intake by the hypothalamus, a growing
body of work indicates that homeostatic mechanisms can be modulated and even overridden
by dopaminergic signaling in the striatum. While the GLP-1 receptor (GLP-1R) is expressed
throughout the brain, GLP-1R signaling in the striatum and in particular the effects on
dopamine (DA) neurotransmission have not yet been elucidated. Here we identify a novel
signaling pathway in the striatum whereby the activation of the GLP-1R decreases nitric
oxide synthase (NOS) activity and as a consequence increases DA transporter (DAT) cell
surface expression. The GLP-1R is specifically localized to the subpopulation of striatal
interneurons expressing neuronal NOS, and GLP-1 signaling decreases NOS activity in rat
striatal slices. GLP-1 and the NOS inhibitor L-NAME both increase DAT cell surface
expression and DA uptake in striatal slices. Importantly, GLP-1R in vivo modulates
behaviors dependent on DA neurotransmission in the striatum, including locomotor activity.
Thus, GLP-1R regulation of nitric oxide signaling and DA homeostasis in the striatum may
contribute to complex behaviors related to food intake as well as to the actions of clinical
drugs targeting GLP-1R signaling to treat diabetes. Furthermore, our results provide a
mechanistic rationale for activation of GLP-1 receptors as a potential therapeutic strategy for
brain disorders characterized by imbalances in DA neurotransmission.
Keywords: dopamine, striatum, nitric oxide, GLP1, diabetes
85. mTOR Signaling and Primary Cilia in Tuberous Sclerosis
Complex
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Eric Armour, Graduate Student
Authors: Eric Armour, Kevin Ess, Ph.D., M.D.
Lab P.I. or Faculty Mentor: Kevin Ess, Ph.D., M.D.
Department or Program: Cell and Developmental Biology
Tuberous Sclerosis Complex (TSC) is a hamartomatous disease of the brain, skin and kidney
that occurs in 1 in 6000 births. Neurological symptoms of TSC, however, are the most severe
and include developmental delays, mental retardation, epilepsy and autism. TSC
pathogenesis is attributed to dysregulation of the mTOR signaling pathway due to mutations
of either the TSC1 or TSC2 gene. mTOR signaling involves two complexes, each containing
mTOR and specific protein binding partners forming mTOR complex 1 (mTORC1) and
mTOR complex 2 (mTORC2). In TSC loss of either TSC1 or TSC2 results in increased
mTORC1 and decreased mTORC2 activity, yet the respective contributions of altered
mTORC1 and mTORC2 signaling to TSC pathogenesis remain unknown. Recent work in our
lab has shown that conditional loss of Tsc1 in the kidney results in cystic kidney disease. This
cystic kidney phenotype can be partially rescued through treatment with rapamycin, an
mTORC1 selective inhibitor. Further analysis of kidney tubules deficient for Tsc1 revealed
longer primary cilia than controls. We hypothesize that mTORC1 and mTORC2 signaling
play important but separate roles in maintaining ciliary function and maintenance. We
hypothesize that disruption of these individual pathways will alter cilia and normal signaling
cascades causing abnormalities of progenitor cell populations. Because the neurological
phenotype of TSC is most severe, we will expand our ciliary analysis to neural progenitor
populations. Using in vivo and in vitro models we will determine the differential effects of
mTORC1 and mTORC2 signaling on cilia length, intraflagellar transport, and ciliary
function. Ultimately, understanding the molecular pathogenesis of TSC is important for the
development of clinical treatments for TSC, autism spectrum disorders and epilepsy, as well
as understanding normal developmental processes.
Keywords: Tuberous Sclerosis, mTOR, cilia, kidney
86. Gene-Gene Interactions Are Associated with Baseline MRI
Measures in Alzheimer’s Disease Neuroimaging Initiative
(ADNI)
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Mary Ellen Koran, Graduate Student
Authors: Mary Ellen Koran, Tricia Thornton-Wells, Ph.D.
Lab P.I. or Faculty Mentor: Tricia Thornton-Wells, Ph.D.
Department or Program: Center for Human Genetics Research
Genetic studies often use binary disease status (present/absent) as the primary phenotype,
or outcome variable. However, studies of complex disease require rich phenotypic
information that can be mapped to distinct genetic etiologies, which may involve gene-gene
or gene-environment interactions. For brain-based diseases, such as Alzheimer disease,
neuroimaging can provide such phenotypic measures, many of which have been shown to
correlate with disease status and to have greater sensitivity in detecting early pathological
changes. In this study, we aimed to test for the association of gene-gene interactions with
MRI measures related to Alzheimers disease using data from the Alzheimer’s Disease
Neuroimaging Initiative (ADNI). The ADNI dataset includes information on rates of change
in cognition, function, brain structure and biomarkers in 200 elderly controls, 400 subjects
with mild cognitive impairment, and 200 patients with mild AD. We used linear regression
analysis to test the ability of 45 previously-implicated SNP-SNP interaction models to
predict 38 different brain region volume and thickness measurements related to AD. We
were able to replicate 6 out of the 45 models in at least 26 of the 38 regions brain regions.
These included NMDA receptors GRIN2A and GRIN2B, protein tyrosine phosphatase
receptors PTPRN2 and PTPRD, sortilin-related receptors SORCS1 and SORCS2, and ERBB4
and INSR. Ultimately using imaging genetics, we hope to identify both genetic and brainbased markers that indicate a predisposition to AD. AD is diagnosed late in disease
progression, and current pharmacological therapies are useful only in early stages of disease.
If such markers could indentify high-risk individuals who should start treatment earlier,
progression of this devastating disease could be slowed, with substantial benefit to patients
and their families, as well as cost-savings to society.
Keywords: imaging genetics, Alzheimer’s disease, neuroimaging, genetics
87. Optical Imaging of Cortical Networks via Intracortical
Microstimulation
Systems Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Andrea Brock, Graduate Student
Authors: Andrea Brock, Robert Friedman, Reuben Fan, Anna Roe, Ph.D.
Lab P.I. or Faculty Mentor: Anna Roe, Ph.D.
Department or Program: Psychology
Cerebral cortex consists of functional neural columns that share specific local connectivity
patterns with other cortical columns and in total form neural networks that lead to
perception and goal directed behavior. Given this cortical organization, it should be possible
to selectively influence cells within a single network to reveal the functional role of identified
cortical columns. Electrical microstimulation has been used previously to generate or alter
percepts and motor behaviors in primates, and several studies have examined global
networks activated by such stimulation using fMRI mapping methods. To examine local
networks we used optical imaging of intrinsic signals to visualize cortical responses to
electrical microstimulation in non-human primates. Stimulation parameters such as current
amplitude and stimulus duration influenced cortical activation, along with depth of
electrode penetration. Furthermore, stimulation produced sites of activation spatially
separate from the electrode where the activation pattern elicited was site dependent, and
parallel known anatomical connections. Future research will focus on using these
stimulation parameters to selectively activate cortical networks.
Keywords: electrical microstimulation, optical imaging of intrinsic signals
88. Knockin Mouse of the Norepinephrine Transporter A457P
Mutation Associated with Human Orthostatic Intolerance
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Jana Shirey-Rice, Ph.D., Postdoctoral Fellow
Authors: Jana Shirey-Rice, Rebecca Klar, Jessica Krueger, Charlene Finney, Suzanna
Lonce, David Robertson, Maureen Hahn, Ph.D.
Lab P.I. or Faculty Mentor: Maureen Hahn, Ph.D.
Department or Program: Genetic Medicine
Norepinephrine (NE) serves as a neurotransmitter in both the brain, where it mediates processes
underlying arousal, attention, memory emotion, and the response to stress, and in the sympathetic
nervous system. Noradrenergic neurotransmission is involved in the pathogenesis of cognitive and
mood disorders including attention deficit hyperactivity disorder (ADHD), major depression and
anxiety as well as cardiovascular diseases. NE released at synapses in the brain and sympathetic
nervous system is actively transported into terminals by the presynaptically-localized norepinephrine
transporter (NET), making it a critical mediator of NE inactivation and presynaptic catecholamine
homeostasis. In the heart, in particular, NET is highly effective in controlling synaptic NE and
manipulations of NET have a profound effect on heart rate. NET is a target for tricyclic
antidepressants, NET-selective reuptake inhibitors, and psychostimulants, all of which have served as
important therapeutics for ADHD and affective disorders. Thus, disruption of NET activity may
produce comorbid psychiatric and cardiovascular symptoms. We previously identified a single
nucleotide polymorphism in the human NET gene, A457P, in a family with incidence of the
cardiovascular disorder, orthostatic intolerance (OI), demonstrating highly elevated heart rate and
plasma NE upon standing. A457P family members were also diagnosed with ADHD. In vitro
expression studies demonstrate that A457P is a loss-of-function transporter with a dominant-negative
influence on wild-type (WT) NET. To study the effects of this mutation in vivo, knockin mice
expressing NET A457P were generated. Adult littermates of the NET A457P knockin mouse line were
examined for total and plasma membrane levels of NET, and NE transport assays were carried out
using synaptosomes from NE terminals in cortex or hippocampus. Basal catecholamines and
metabolites were measured in urine collected from WT, A457P heterozygous knockin (A457P HET),
and A457P homozygous knockin (A457P HOM) mice using HPLC with electrochemical detection. In
A457P HET mice, surface levels of NET and transport were both significantly reduced in cortex and
hippocampus; surface NET was further decreased in A457P HOM animals, and an almost complete
loss of transport was observed in cortical and hippocampal synaptosomes. Interestingly, despite only
a ~50% decrease in surface NET levels, transport levels were only 6-8% of WT. Measurement of basal
NE and 3,4-dihydroxyphenylglycol (DHPG), a product of intraneuronal NE metabolism, in urine of
these mice revealed significant decreases in the DHPG/NE ratio. These changes in catecholamine
biochemistry recapitulate clinical changes observed in human carriers. These data demonstrate that
A457P is both trafficking- and activity-deficient in neurons in vivo. Future studies will determine the
contribution of NE transport deficiency to the tachycardia and cognitive symptoms observed in
human A457P carriers. Disruption in genes, such as NET, with shared expression in the brain and
autonomic nervous system may contribute to comorbidity of psychiatric and cardiovascular diseases.
Keywords: transporters, norepinephrine, mutation, ADHD, orthostatic intolerance
89. Neurocognitive Deficits in Survivors of Pediatric ALL:
Implications for Long-Term Coping and Emotion Regulation
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Kristin Robinson, Graduate Student
Authors: Kristen Robinson, Charissa Andreotti, Michelle Reising, Jennifer
Champion, Laura Campbell, Jennifer Potts, Kelly Haker, Bruce Compas, Ph.D.
Lab P.I. or Faculty Mentor: Bruce Compas, Ph.D.
Department or Program: Psychology and Human Development
Objectives: Research on late effects of pediatric acute lymphocytic leukemia (ALL) has
found that a significant number of survivors experience long-term psychosocial and
neurocognitive deficits (Campbell et al., 2006). Possible associations between these areas
may contribute to understanding the behavioral and emotional functioning of these children
and their ability to cope with stress, but these associations have not been studied.
Participants and Methods: We assessed neurocognitive functioning of 46 survivors of
ALL (22 females, mean age = 14.05 years, SD = 2.89) using the Working Memory (WMI)
and Processing Speed (PSI) Indices of the WISC-IV and the Metacognition Index of the
BRIEF. Survivors and parents also completed the Responses to Stress Questionnaire, a
measure of survivors’ coping and emotion regulation.
Results: Greater deficits in executive functioning on the BRIEF were associated with
decreased use of secondary control coping (e.g., cognitive reappraisal; r = -.46, p = .002)
according to survivors’ self-report, and were associated with decreased use of primary
control (e.g., problem solving; r = -.55, p < .001) and secondary control coping (r = -.33, p =
.034) and increased use of disengagement coping (r = .36, p = .020) according to parent
report. Higher scores on the WMI were associated with greater use of primary control
coping (r = .42, p = .007) according to parent report.
Conclusions: These findings suggest that survivors experiencing executive function deficits
may be less likely to use adaptive coping strategies when facing stress, and suggest broader
implications for the cognitive and potential neurobiological substrates of coping and
emotion regulation.
Keywords: coping, emotion regulation, pediatric leukemia
90. The Relationship Between White Matter Connectivity and
Children’s Reading Abilities
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Qiuyun Fan, Graduate Student
Authors: Qiuyun Fan, Nicole Davis, Ph.D., Donald Compton, Ph.D., Douglas Fuchs,
Ph.D., Lynn Fuchs, Ph.D., Laurie Cutting, Ph.D., John Gore, Ph.D., Adam Anderson,
Ph.D.
Lab P.I. or Faculty Mentor: Donald Compton, Ph.D., Douglas Fuchs, Ph.D., Lynn
Fuchs, Ph.D., Laurie Cutting, Ph.D. John Gore, Ph.D., Adam Anderson, Ph.D.
Department or Program: Biomedical Engineering
Introduction: While responsiveness to intervention (RTI) is used to identify students with
disabilities, the relationship between RTI and the neurobiological characteristics of a student remains
unclear. The relationship between activation and response to instruction has been reported in a few
functional MRI studies; however, whether a similar correlation exists with white matter (WM) is
unknown. The purpose of the current study was to investigate the potential relationship between WM
connectivity and responsiveness to classroom based reading instruction in children, using diffusion
tensor imaging (DTI) analysis.
Methods: Behavioral administration. 11 children with a mean age of 7.5 years (SD = .43), including
control participants, were screened and determined to be at-risk for reading difficulties at the
beginning of first grade. Upon conclusion of a year-long reading intervention, the participants were
categorized into controls (C), responders (R) and non-responders (NR) according to their
responsiveness to the intervention. Behavioral measures were administered, including word
identification fluency (WIF), untimed word identification skill (WID), untimed decoding skill (WAT),
sight word reading efficiency (SWE), and phonemic decoding efficiency (PDE).
Image processing. Structural and diffusion weighted images were acquired on a 3T Philips scanner.
As for the diffusion weighted images, 10 non-diffusion weighted and 92 diffusion weighted image
volumes were acquired with a diffusion weighting factor of 1600 s/mm2 (i.e., b=1600 s/mm2). A
whole brain parcellation was performed in FreeSurfer, and 18 regions of interest (ROI) identified as
related to reading in previous studies were then selected to be analyzed. A probabilistic tractography
algorithm implemented in FSL, was used to quantify the connectivity among these gray matter
regions, and thus a connectivity matrix was constructed for each participant.
Results: We found some reading behavioral scores are significantly correlated to the connectivity
between some cortical/sub-cortical region pairs. In particular, increased score on each of the reading
measures is related to greater strengths of connectivity between the left angular gyrus (ANG) and
insula (INS), meaning the NR participants generally have lower connectivity than R or C participants.
Similarly, performance on the WAT subtest correlated positively with connectivity values between
pars triangularis (TRI) to inferior frontal sulcus (IFS) - NR participants had lower connectivity than R
or C participants.
Discussion: Our results indicate that the information transfer pathways between anatomical regions
related to reading are significantly correlated with particular reading abilities. Furthermore, our
findings extend the knowledge of WM differences related to reading skills by demonstrating
correlations with the participants’ level of responsiveness to reading instruction.
Keywords: connectivity, reading ability, diffusion tensor imaging
91. Presynaptic Regulators of Dopamine Homeostasis:
A Worm’s Tale
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Andrew Hardaway, Graduate Student
Authors: Andrew Hardaway, Sarah Whitaker, Shannon Hardie, Sarah Baas, Randy
Blakely, Ph.D.
Lab P.I. or Faculty Mentor: Randy Blakely, Ph.D.
Department or Program: Pharmacology
The catecholamine neurotransmitter dopamine (DA) modulates multiple behavioral
processes in humans including learning, arousal, reward, cognition and motor control;
faculties disrupted in neuropsychiatric and neurodegenerative disorders such as bipolar
disorder, schizophrenia, and Parkinson’s Disease. Overall DA signaling is regulated by
modulation of the neurotransmitter’s biosynthesis, packaging, release, metabolism and
receptor activation, but the temporospatial actions of DA are controlled by the presynaptic
dopamine transporter (DAT). DATs clear synaptic DA via Na+/Cl--dependent uptake,
returning the catecholamine to the presynaptic terminal where it is repackaged and rereleased. In C. elegans, DAT-1 supports DA reuptake, is expressed solely within DA neurons,
preferentially transports DA, and is blocked by psychoactive compounds such as cocaine and
amphetamine. Our previous studies show that DAT-1 is an important modulator of
endogenous DA levels as dat-1 worms exhibit a DA-dependent locomotory phenotype
termed Swimming Induced Paralysis (SWIP). SWIP is mediated by an increase in
extrasynaptic DA, as dat-1 animals are rescued by reserpine-induced depletion of DA from
synaptic vesicles, loss of DA biosynthesis (cat-2) or with loss of the postsynaptic receptor
DOP-3. In the current study, we utilized the SWIP phenotype to pursue a forward genetic
screen that identifies hyperdopaminergic mutants. To date, we have screened ~10,000
haploid genomes and we have isolated 12 stable lines representing at least four
complementation groups. We have thoroughly characterized two of these lines, swip2 and
swip3, demonstrating that they harbor loss-of-function mutations in DAT-1 coding
sequences, providing vital proof-of-concept evidence that our screen targets genes involved
in the presynaptic regulation of DA signaling. We describe the locomotive behaviors and
mapped chromosomal loci of additional swip mutants, and current efforts are utilizing
whole genome sequencing to identify the molecular lesion in these strains. Recent evidence
demonstrates that the presynaptic autoreceptor DOP-2s is required for maintenance of
normal swimming behaviors, and behavioral analysis of these mutant strains suggests that
they may exhibit enhanced DA release and may harbor mutations in genes required for
coupling autoinhibition and DA clearance.
Keywords: dopamine, forward genetics, dopamine 2 receptor, transporters, behavioral screening
92. Attitudes Regarding Inclusion of Students with Intellectual
Disabilities at College
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Megan Griffin, Graduate Student
Authors: Megan Griffin, Elise McMillan, J.D., Tammy Day, Allison Summer, Robert
Hodapp, Ph.D.
Lab P.I. or Faculty Mentor: Robert Hodapp, Ph.D.
Department or Program: Vanderbilt Kennedy Center
Introduction: Post-secondary education (PSE) is an increasingly viable option for students
with intellectual disabilities (ID). However, little is known about the attitudes of typical
college students toward their inclusion at college. Therefore, we surveyed typical students at
Vanderbilt during the first semester of a pilot PSE program, Next Steps at Vanderbilt.
Methods: Participants were 256 undergraduates at Vanderbilt who responded to a
confidential survey about their attitudes toward including students with ID. The survey was
composed of 35 items, most of which involved ratings on a 5-point scale (1=least, 5 =most).
The survey addressed students’ demographics, perceptions of the abilities of people with ID,
willingness to interact with students with ID, and perceived benefits or concerns related to
including students with ID at college.
Results: Overall, respondents indicated positive attitudes toward students with ID;
however, some characteristics were correlated with more positive attitudes. For example,
respondents with closer relationships to people with ID were more willing to interact with
students with ID (r = 0.323, p < .01), and perceived more benefits associated with their
inclusion (r = 0.234, p < .01). Also, females had more positive perceptions of the abilities of
people with ID, F(1, 251) = 9.47, p = .002; were more willing to interact with students with
ID, F(1, 252) = 21.07, p < .01; and perceived more benefits associated with their inclusion,
F(1, 244) = 43.85, p < .01. Respondents who were more comfortable with people with ID had
more positive perceptions of the abilities of people with ID (r = 0.285, p < .01); perceived
more benefits associated with their inclusion (r = 0.301, p < .01); and were more willing to
interact with them (r = 0.435, p < .01). Findings regarding concerns associated with the
inclusion of students with ID were less consistent.
Discussion: Survey responses demonstrate positive attitudes toward the inclusion of
students with ID on college campuses; however, group differences were found. Female
respondents and those who reported a higher comfort level with people with ID had more
positive perceptions of students with ID, and more positive attitudes toward their inclusion.
Keywords: inclusion, postsecondary education
93. An APPL1Akt Signaling Complex Regulates Dendritic
Spine and Synapse Formation in Hippocampal Neurons
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Devi Majumdar, Ph.D., Postdoctoral Fellow
Authors: Devi Majumdar, Ph.D., Caroline Nebhan, Lan Hu, Bridget Anderson,
Donna Webb, Ph.D.
Lab P.I. or Faculty Mentor: Donna Webb, Ph.D.
Department or Program: Biological Sciences
The formation and plasticity of dendritic spines and synapses, which are poorly understood
on a molecular level, are critical for cognitive functions, such as learning and memory. The
adaptor protein containing PH domain, PTB domain, and leucine zipper motif (APPL1) is
emerging as a critical regulator of various cellular processes in non-neuronal cells, but its
function in the nervous system is not well understood. In this study, we show that APPL1
localizes to dendritic spines and synapses and regulates the development of these structures
in hippocampal neurons. Knockdown of endogenous APPL1 using siRNA led to a significant
decrease in the number of spines as well as synapses and this defect could be rescued by
expression of siRNA-resistant APPL1. Expression of exogenous APPL1 increased the spine
and synaptic density and the amount of surface GluR1-containing -amino-3-hydroxy-5methyl-4-isoxazole propionic acid receptors (AMPARs). Deletion of the C-terminal
phosphotyrosine binding domain of APPL1, which binds the serine/threonine kinase Akt,
resulted in a significant decrease in the spine and synaptic density, suggesting to a role for
Akt in regulating the development of these structures. Consistent with this, knockdown of
Akt with siRNA or expression of dominant negative Akt led to a dramatic decrease in spine
and synapse formation. In addition, APPL1 increased the amount of active Akt in spines and
synapses and the effect of APPL1 on these structures was dependent on Akt, indicating Akt is
an effector of APPL1 in the regulation of these processes. Moreover, APPL1 signaling
modulates spine and synapse formation through p21-activated kinase (PAK). Thus, our
results indicate APPL1 signaling through Akt and PAK is critical for spine and synaptic
development and point to a role for APPL1 and its effectors in regulating cognitive functions.
Keywords: dendritic spines, synapse formation, AMPA receptors, APPL1 , Akt
94. Respiratory Sinus Arrhythmia Prior and During
Narratives of Preschool-Age Children Who Stutter:
A Methodological Study
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Robin Jones, Graduate Student
Authors: Robin Jones, Edward Conture, Ph.D., Tedra Walden, Ph.D.
Lab P.I. or Faculty Mentor: Edward Conture, Ph.D., Tedra Walden, Ph.D.
Department or Program: Hearing and Speech Sciences
Purpose: The purpose of this study is to assess cardiac vagal tone of preschool-age children
who stutter (CWS) and children who do not stutter (CWNS) during emotionally-arousing
situations.
Participants: Participants will be X preschool-age CWS and X preschool-age CWNS,
matched for age and gender.
Methods: Participants will be exposed to two emotion-inducing child video clips – angry
and positive, with neutral clips used to establish pre- and post-arousal baselines, and then
perform age-appropriate narrative tasks. Cardiac vagal tone, as indexed by respiratory sinus
arrhythmia (RSA), will be measured while participants listen to/watch an audio-video clip
presentation and perform the narrative task.
Results: Results will be used to assess the hypothesis that CWS, when compared to CWNS,
will exhibit RSA during the emotionally-arousing situations.
Conclusions: Findings will be used to evaluate the possibility that vagal tone, associated
with emotional arousal, may be related to subtle, but important changes in the speech
(dis)fluency of children who stutter.
Keywords: stuttering, physiology, respiratory sinus arrhythmia, narrative, vagal tone
95. Age-Dependent Changes in Striatal Signaling Protein
Complexes
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: A. J. Baucum, Ph.D., Postdoctoral Fellow
Authors: A. J. Baucum, Ph.D., Roger Colbran, Ph.D.
Lab P.I. or Faculty Mentor: Roger Colbran, Ph.D.
Department or Program: Molecular Physiology and Biophysics
Excitatory synaptic transmission depends on proper organization of neurotransmitter
receptors in dendritic spines, protrusions from neuronal dendrites that are highly enriched
in F-actin-based cytoskeletal elements and the signaling machinery required for synaptic
plasticity. In the rodent, spines located on striatal medium spiny neurons typically begin to
appear around postnatal day (P) 12, and their shape and number are continuously modified
during normal development into adulthood (P90) and during senescence (up to 2 years of
age). Spine numbers and/or morphology are often altered in developmental disorders (e.g.,
Fragile-X, Rett, and Down syndromes) and in aging-related neurological disorders such as
Parkinson disease (PD). Although the biochemical signaling mechanisms that regulate agedependent and pathological changes in dendritic spine density are poorly understood,
spinophilin was identified as a dendritic spine enriched protein that can regulate dendritic
spine numbers during development, in part due to its interactions with multiple proteins
such as F-actin and protein phosphatase 1 (PP1). Moreover, we found that in adulthood the
interactions of PP1 with spinophilin are enhanced in a rodent model of PD. To enhance our
knowledge of striatal dendritic spine signaling, we utilized a mass spectrometry based
proteomics approach to identify additional spinophilin-associated proteins (SpAPs) in adult
animals. Interestingly, calcium/calmodulin-dependent kinase II (CaMKII), was detected as
a putative SpAP. CaMKII is an important regulator of dendritic spine morphology and
synaptic activity, in part due to its regulation of downstream proteins such as glutamate
receptors. Autophosphorylation of CaMKII regulates its activity, and CaMKII
autophosphorylation is altered during development and in animal models of PD. Here we
identify multiple domains on spinophilin that directly bind to CaMKII and show that the
interaction between spinophilin and CaMKII is regulated by autophosphorylation of the
kinase and is increased in striatal lysates isolated from adult compared to P21 animals.
Furthermore, the targeting of PP1 to CaMKII is increased in striatal lyastes isolated from
aged compared to P21 animals. These data suggest an age-dependent mechanism for
CaMKII targeting to a unique subset of substrates that are also SpAPs, and which may
underlie age- and/or disease-dependent changes in dendritic spine numbers and/or
morphology in the striatum.
Keywords: Parkinson’s disease, signaling, dendritic spines, aging
96. The Balloon Analog Insurance Task BAIT: A Novel
Measure of Protective Risk Management
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Brian Essex, Graduate Student
Authors: Brian Essex, Carl Lejuez, Rebecca Qian, Katie Bernstein, David Zald, Ph.D.
Lab P.I. or Faculty Mentor: David Zald, Ph.D.
Department or Program: Psychology
Introduction: Prior methods used to assess individual differences related to risk have not
paid attention to an important component of risk management. Specifically, they have not
looked at how willing individuals are to pay for or take actions to insure what they already
have. It is not clear whether this type of protective risk management taps into the same
individual differences as does risk taking propensity measured by other risk taking tasks.
We developed a novel task to assess this type of protective risk management, the Balloon
Analog Insurance Task (BAIT), which is modeled after the Balloon Analog Risk Task
(BART). In the BAIT, individuals are forced to decide how much money they are willing to
pay in order to insure a specific fraction of their prior winnings given changing but imprecise
levels of risk of monetary loss.
Methods: 128 individuals between the ages of 18 and 30 completed the BART and BAIT for
real monetary rewards. They also completed the following self-report measures: the
Obsessive-Compulsive Inventory (OCI-R), the short form of the Psychopathic Personality
Inventory (PPI), the Intolerance of Uncertainty Scale (IUS), and the Domain Specific Risk
Taking Questionnaire (DOSPERT).
Results: The amount of insurance purchased on the BAIT was positively correlated with
scores on the IUS and the checking subscale of the OCI-R. Conversely, the amount of
insurance purchased was negatively correlated with scores on the DOSPERT and PPI.
Furthermore, these relationships continued to be significant when controlling for the BART
in linear regression analyses and the BART was not a significant predictor.
Discussion: Behavior on the BAIT taps into a number of individual differences that are
not related to behavior on another measure of risk taking. We propose that the BAIT may
provide a useful complement to the BART or other risk assessment tasks.
Keywords: risk taking, individual differences, protective risk management
97. Effects of Chronic Ethanol Exposure on Excitatory
Transmission in the Dorsal-Lateral Bed Nucleus of the stria
terminalis: Assessing Contributions of GluN2B with Ro256981
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Tiffany Wills, Ph.D., Postdoctoral Fellow
Authors: Tiffany Wills, Ph.D., Jason Klug, Y. Silberman, Eric Delpire, Ph.D., Danny
Winder, Ph.D.
Lab P.I. or Faculty Mentor: Eric Delpire, Ph.D., Danny Winder, Ph.D.
Department or Program: Molecular Physiology and Biophysics
Acute and chronic ethanol administration modulate glutamate transmission via actions on
NMDA receptors (NMDARs). Much effort has gone into determining whether NMDAR
subunit specificity plays a role in these effects of ethanol. So far, results have been mixed, at
least in part based on the region examined. Work in the extended amygdala (ventral bed
nucleus of the stria terminalis, vBNST, and central nucleus of the amygdala) using
pharmacological approaches has suggested a preferential modulation of the GluN2B subunit
following chronic ethanol treatments. The current work set out to determine if GluN2B was
also preferentially altered (using GluN2B antagonist, Ro25-6981) by chronic ethanol in the
dorsal lateral (dl) BNST, as this general region has been implicated in anxiety and
withdrawal-associated behaviors. To do this, we evaluated two 4-day cycles of chronic
intermittent ethanol exposure (CIE) on LTP and NMDAR responses in the dlBNST 4-5 hrs
into withdrawal in the presence and absence of the GluN2B selective antagonist Ro25-6981
(Ro). Interestingly, LTP was blunted in mice exposed to chronic air treatment compared to
naïve mice, suggesting that the sham condition may be stressful. In ethanol treated mice
LTP was similar to naïve mice, suggesting that ethanol either prevents stress effects seen in
the air-treated group or produces an enhancement in excitatory transmission which
alleviated blunted LTP. We hypothesize that ethanol treatment enhances BNST LTP in a
GluN2B selective manner and, therefore, investigated the effects of Ro in these groups.
Intriguingly, we observed a selective enhancement of LTP by Ro in ethanol exposed mice. Ro
did not alter LTP in either naïve or air-controls. Lastly, Ro application enhanced
extracellularly recorded NMDAR responses in both naïve and ethanol-treated mice. These
results suggest that the ethanol treatment causes adaptations in excitatory transmission in
the dlBNST that were selectively potentiated by Ro application. The Ro enhancement
illustrated by these data are paradoxical considering the reported selective antagonism of Ro
at the GluN2B subunit of NMDARs. Future studies will use GluN2B KO mice to specifically
address this paradoxical enhancement of Ro following ethanol treatment and if ethanol is
selectively enhancing LTP in a GluN2B dependent manner.
Keywords: addiction, anxiety, GluN2B, BNST, ethanol
98. The Effect of Deep Brain Stimulation on Frontal Activity
During Working Memory in Parkinson’s Disease: A NearInfrared Spectroscopy Study
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Jutta Mayer, Ph.D., Postdoctoral Fellow
Authors: Jutta Mayer, Ph.D., Sarah Bourne, Bradley Folley, Joseph Neimat, Sohee
Park, Ph.D.
Lab P.I. or Faculty Mentor: Sohee Park, Ph.D.
Department or Program: Psychology
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD)
improves the cardinal motor symptoms and increases frontal blood flow, however the effects
on cognition are highly variable and remain poorly understood. In the present study we used
near-infrared spectroscopy to examine the effects of STN-DBS and dopaminergic medication
in early PD patients on brain activation in the frontal cortex during a spatial working
memory (WM) task. The task required participants to maintain three target locations in
WM. PD patients who underwent DBS were tested on and off DBS. Patients who received
medication only were tested on and off medication. We examined oxyhemoglobin
concentrations in the frontal cortex during the delay period of the WM task. Preliminary
findings show that both DBS and dopaminergic medication slightly decreased WM accuracy.
The DBS and medication-induced declines in behavioral performance were accompanied by
an increase in the concentrations of oxyhemoglobin in the right frontal cortex. These
findings suggest that STN-DBS might impair spatial WM processes due to alterations in the
associative cortico-basal ganglia-thalamocortical circuit. In addition, these findings provide
direct evidence for a functional interplay between subcortical (STN) and cortical (frontal)
regions involved in WM maintenance.
Keywords: deep brain stimulation, Parkinson’s disease, working memory, near-infrared spectroscopy,
frontal cortex
99. Effect of Certain Environmental Metals on the Early Stages
of Human Neuronal Development
Cellular and Molecular Neuroscience (Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Asad Aboud, M.D., Postdoctoral Fellow
Authors: Asad Aboud, M.D., Andrew Tidball, Diana Neely, Ph.D., Michael Litt,
Charles Hong, Kevin Ess, Ph.D., M.D., Aaron Bowman, Ph.D.
Lab P.I. or Faculty Mentor: Diana Neely, Ph.D., Kevin Ess, Ph.D., M.D., Aaron
Bowman, Ph.D.
Department or Program: Neurology
Gene-environment interactions are a well-established theme in the pathophysiology of
neurodegenerative diseases. Characterizing the nature of these interactions and the main
players is an important goal. While much important work has been done using animal
models, it is uncertain how applicable these results are to the human. In addition, the nature
of these interactions during early human CNS development has not been clearly elucidated.
Our lab has succeeded in making induced pluripotent stem cells from patients with welldefined genetic mutations associated with neurodegeneration. In this study we used stem
cells from patients with PARK2 mutations, TSC1 mutations, chromosome 21 and 12 trisomy,
and normal controls to investigate the toxicity of copper, methylmercury, manganese, and
cadmium on early stage of neuronal progenitors. We were able to demonstrate increased
vulnerability of PARK2 mutated neuroprogenitor cells to copper and cadmium compared to
cells from the healthy control. This finding demonstrates the utility of our models to study
the gene-environment interactions in a patient-specific manner. Furthermore, it opens the
door to high throughput screening for the specific gene interactions with a wide array of
toxicants and other environmental agents.
Asad Aboud and Andrew Tidball contributed equally to this work.
Keywords: stem cells, gene-environment interaction, neuron development, environmental metals,
patient-specific toxin screen
100. He Said She Said: Difficulties in Non-Native Speech
Perception Revealed by Changes in Speaker Identity
Systems Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Chang Gu, Graduate Student
Authors: Chang Gu, Yuliya Yoncheva, Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
Natural speech is an acoustically complex and variable signal, yet native listeners readily
extract reliable phonetic information across multiple speakers. Phonetic perception is
shaped by language experience, as evidenced by sharpened phonetic perceptual abilities for
native versus non-native contrasts. Correspondingly, lack of experience with a particular
language has been linked to difficulties in discriminating non-native phonetic contrasts. This
challenge might be especially exacerbated when extracting phonetic information across
different speakers. We propose that subtle individual variations in the stability of phonetic
representations might be revealed by a task that requires generalization across speakers. To
test this, the present study examines non-native and native speakers’ performance on
phonetic discrimination under conditions of competition along two distinct stimulus
dimensions (i.e., speaker vs. phoneme). Native English and Chinese speakers completed an
ABX task: they listened to a pair of Chinese syllables, each one of four phonemes (/dse/,
/tse/, /je/, and /che/), and reported which of the two syllables contained the same phoneme
as a subsequent third syllable. Additionally, each syllable could be spoken by a male or
female speaker, allowing the investigation of competition effects between stimulus
dimensions within a pair. On half of the trials, the speaker identity was congruent with
phonetic information, such that the similarity of speaker identity biases subjects toward
correct phonetic decisions. The other half presented incongruent phonetic and speaker
identity information, so the irrelevant speaker identity information biased responses toward
incorrect phonetic decisions. Reaction time and accuracy measures showed that Chinese
speakers were uninfluenced by the congruence of speaker and native phonetic identity.
English speakers, however, revealed a large congruence effect: their accuracy was
significantly lower on incongruent than on congruent trials, especially for the non-native
phonetic contrasts that were least similar to English contrasts. These findings indicate that
phonetically irrelevant changes in speaker identity impact speech perception in a differential
manner, which scales with experience with a specific language. This paradigm provides a
means of quantifying the degree to which speakers create robust phonetic representations
that support processing of natural speech variation.
Keywords: speech perception, language experience, non-native phonetic representations
101. Social Trait Judgment and Affect Recognition from Static
Faces and Video Vignettes in Schizophrenia
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Lindsey Gilling McIntosh, Undergraduate Student
Authors: Lindsey Gilling McIntosh, Sohee Park, Ph.D.
Lab P.I. or Faculty Mentor: Sohee Park, Ph.D.
Department or Program: Psychology and Human Development
Background: Previous research has shown impairment in affect recognition in individuals
with schizophrenia (SZ). Poor affect recognition has been associated with more severe
symptoms and poor social functioning. Few studies have examined the quality of social
judgments made by individuals with SZ, with mixed findings. Research in nonclinical
populations suggests healthy people can accurately judge many social traits of others from
brief exposure to nonverbal cues. The current study examined the quality of social
judgments made by schizophrenic outpatients from both photos of emotional faces and
short videos, rich with nonverbal cues.
Methods: Outpatients with SZ and demographically matched healthy controls (HC)
participated in affect recognition and social trait judgment tasks. Forty-two stimuli from the
Karolinska Directed Emotional Faces were used for affect recognition from static photos,
and 35 video clips of 15s each selected from The Awareness of Social Inference Test
comprised the vignettes. Sound was removed from the video. Participants viewed each face
and video clip, and made judgments about the emotional state, attractiveness,
trustworthiness, approachability, and intelligence of the actor(s). Clinical symptoms (SANS,
SAPS), current mood (PANAS), psychosis-proneness (SPQ for controls), delusions (PDI),
and social functioning (SFS) data were assessed and the Eyes test was given to index the
Theory of Mind (ToM).
Results: SZ patients were impaired relative to HC on affect recognition for both static and
video stimuli. This impairment may be related to patients’ severity of positive symptoms.
While patients and controls make similar trait judgments, those which patients make are
significantly related to positive and negative symptom severity. Likewise, PDI scores from
HC are significantly correlated with their judgments of attractiveness, trustworthiness, and
approachability. The relationship between these findings and social functioning and ToM
remains unclear.
Conclusion: These results indicate that SZ is associated with impaired affect recognition
and psychotic symptoms are related to abnormal trait attribution. Considering the
importance of accurate social trait judgment in everyday interactions and the potential role
of impaired trait judgment in paranoid ideation, our finding of anomalous social trait
judgment in SZ patients is intriguing.
Keywords: social cognition, affect, social trait, nonverbal, schizophrenia
102. Persistent Structural Brain Changes Following in utero
Alcohol Exposure
Systems Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Kristen Eckstrand, Graduate Student
Authors: Kristen Eckstrand, Joseph Jacobson, Ph.D., Ronald Cowan, M.D., Ph.D.,
Sandra Jacobson, Ph.D., Malcolm Avison, Ph.D.
Lab P.I. or Faculty Mentor: Ronald Cowan, M.D., Malcolm Avison, Ph.D.
Department or Program: Vanderbilt University Institute for Imaging Science
Prenatal exposure to alcohol (PNAE) results in sustained behavioral and neurocognitive
deficits, including those observed in attention deficit hyperactivity disorder (ADHD)
(Mattson et al. 1996, Coles et al. 1997, Jacobson et al. 2002b, Jacobson et al. 2004).
Structural brain imaging studies have identified specific abnormalities in children and
adolescents exposed to high levels of alcohol in utero, one or more of which have been
suggested to underlie these deficits (Archibald et al., 2001; Sowell et al., 2002; Riley et al.,
2004). It remains unclear, however, whether these abnormalities are observed with lower
levels of exposure, and if they are, whether they persist into adulthood. Using structural MRI
scans obtained from a well-controlled, homogeneous cohort of young African-American
adults (18-21 y.o.) whose in utero exposure was carefully monitored throughout pregnancy,
and voxel-based morphometry (VBM), we tested the hypothesis that low to moderate PNAE
is associated with subtle structural brain changes that persist into adulthood. Consistent
with the low exposures, we found no difference in total gray (GM) or white matter (WM)
volumes between PNAE (n=11) with healthy non-exposed volunteers (n=9). However PNAE
individuals had significantly reduced GM volume in the left cingulate gyrus, right middle
frontal gyrus, right middle temporal gyrus, and right caudate nucleus. Furthermore, there
was a significant dependence of GM loss on in utero alcohol dose in all of these regions,
suggesting that even low levels of foetal alcohol exposure may have a long-lasting impact on
brain structure.
Keywords: prenatal alcohol exposure, voxel-based morphometry, ADHD, neuroimaging
103. Communicative and Psychological Dimensions of the
KiddyCAT
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Chagit Edery Clark, Graduate Student
Authors: Chagit Edery Clark, Edward Conture, Ph.D., C. Frankel, Tedra Walden,
Ph.D.
Lab P.I. or Faculty Mentor: Edward Conture, Ph.D., Tedra Walden, Ph.D.
Department or Program: Hearing and Speech Sciences
The purpose of this study was to investigate the underlying constructs of the Communication
Attitude Test for Preschool and Kindergarten Children Who Stutter (KiddyCAT;
Vanryckeghem & Brutten, 2007). Extant KiddyCAT responses of 114 preschool-age children
who do and do not stutter were subjected to a principal components factor analysis (PCA).
Results indicate that a single dimension – speech difficulty - accounts for or underlies the
KiddyCAT. Findings should further our understanding of how attitudes and/or awareness
may contribute to developmental stuttering in preschool-age children.
Keywords: stuttering, KiddyCAT, attitudes, assessment
104. A Role for a BRG1-NFĸB Complex During Peripheral
Nerve Myelination
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Allison Limpert, Ph.D., Postdoctoral Fellow
Authors: Allison Limpert, Ph.D., Ying Chen, Q. Richard Lu, Bruce Carter, Ph.D.
Lab P.I. or Faculty Mentor: Bruce Carter, Ph.D.
Department or Program: Biochemistry
In the developing peripheral nervous system, axonal derived signals stimulate Schwann cells
to undergo a global genetic reprogramming where they cease cellular division and turn on
genes specific for myelin formation. Our lab has identified NFĸB as a pivotal transcription
factor for Schwann cell differentiation, however, the mechanism by which NFĸB elicits its
effects on the developing Schwann cells remains to be elucidated. Here we report that NFĸB
specifically interacts with BRG1, the central ATPase of the Swi/Snf related chromatin
remodeling complex in myelinating cells, allowing it to have wide reaching effects on gene
expression. BRG1 is a helicase which has been shown to play a critical role in the
differentiation of neurons, muscle cells and adipocytes. We found that BRG1 is highly
expressed in isolated Schwann cells and in the developing sciatic nerve in perinatal animals,
when myelin is beginning to form, but is down regulated as myelination progresses. The
ATPase activity of BRG1 mimics its expression and is elevated in myelinating cells. BRG1
interacts with NFĸB in a neuregulin dependent manner and forms a DNA binding complex
with NFĸB during myelin formation in DRG- Schwann cell co-cultures and in developing
sciatic nerves. This NFĸB-BRG1 complex may affect the activity of the BRG1 protein as both
the overexpression of NFĸB and the stimulation of NFĸB-DNA binding resulted in an
increase BRG1 ATPase activity. Further examination of BRG1-containing chromatin
remodeling complexes in Schwann cells revealed that these complexes differ in subunit
composition when compared to other developing tissues. Additionally, the BRG1 homolgous
protein, BRM, was unable to interact with NFĸB in myelinating cells. These data suggest the
existence of a BRG1-NFĸB containing chromatin remodeling complex specific for Schwann
cell myelination.
To examine the requirement for BRG1 in Schwann cell differentiation, floxed brg1 mice were
crossed with desert hedgehog (Dhh)-Cre mice. Preliminary analysis suggests marked
disruption of myelin formation and quantitative analysis is currently being performed.
Together our data suggest that BRG1 is required for Schwann cell differentiation and that
this helicase is targeted to myelin specific genes, at least in part, through forming a complex
with NFĸB.
Keywords: BRG1, NFkB, Schwann cell, myelin, chromatin remodeling
105. Constraint-Induced Movement Therapy Improves Neural
Processing and Neurobehavioral Function in Children with
Cerebral Palsy
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Ashley Simmons, Graduate Student
Authors: Ashley Simmons, Alexandra Key, Ph.D., G. Henderson, S. Gogliotti, Amber Vinson, Dorita
Jones, Natalie Maitre, Ph.D., M.D.
Lab P.I. or Faculty Mentor: Natalie Maitre, Ph.D., M.D.
Department or Program: Neonatology
Background: Cerebral palsy (CP) is a non-progressive disorder of movement for which there exist few
evidence-based therapies.
Objective: To combine neurobehavioral, electrophysiological and neuroimaging assessments to quantify the
effect of constraint-induced movement therapy (CIMT) on neural and behavioral function.
Design/Methods: Prospective study of a 1-week intensive camp of CIMT in 10 children (5-12 years) with
hemiparetic CP associated with neonatal brain lesions. Standardized neurobehavioral and sensory
assessments of upper extremity function were correlated with latency and amplitude of event-related
potentials (ERPs) in response to 2 established paradigms targeting speed and efficiency of brain processing.
Results: CIMT had a strong positive effect on neurobehavioral and electrophysiologic function and the two
were often correlated.
PMAL (median, IQR)
Total
How Often
How Well
QUEST (median, IQR)
Total
Dissociated Movement
Grasp
Weight Bearing
Protective Extension
Two Point Discrimination (mm)
(median, IQR)
Grip Strength (median, IQR)
(affected/unaffected )
Developmental Disregard
Index (median, IQR)
 T2-T1
P value for 
T2-T1
<0.001
<0.001
<0.001
0.11
0.17
0.81
0.001
0.29
0.05
Correlation of 
T2-T1 with ERP
measures
0.73
0.76
0.89
0.83
NS
NS
0.89
NS
0.87
3.4 (3.,3.8)
2 (1.9,2.4)
1.3 (1.2,1.5)
3.9 (0.3,10.5)
1.6 (0,6.2)
0 (-5.6,1.8)
6 (4,9)
5.6 (-2.3,15.3)
-1 (-2,0)
0.04
0.03
<0.01
0.01
NS
NS
<0.01
NS
0.03
0.1 (0.1,0.2)
0.01
0.77
0.02
-58.3 (-75,-49)
<0.001
0.77
0.02
P value for
correlation
 T2-T1: change post-pre CIMT, PMAL: Pediatric Motor Activity Log, QUEST: Quality of Upper
Extremity Skills Test, Developmental Disregard Index: QUEST-(PMAL/5X 100%)
ERPs also indicated improvements in processing function in children with left-sided brain
lesions with shorter latencies on the contralateral side after CIMT (F = 26.8, p = 0.001).
Conclusions: Neurobehavioral assessments can be combined with ERP to quantify improvements in neural
function after CIMT. To assess for persistence of effects, neurobehavioral and ERP testing will be repeated 6
months post-CIMT and correlated with neuroimaging findings. Our multimodal assessment model holds
promise for evidence-based therapy design in children with CP.
Keywords: cerebral palsy, constraint-induced movement therapy, hemiparetic CP
106. Anatomical Connectivity Patterns of the Anterior
Ectosylvian Sulcus: Implications for Multisensory
Processes
Systems Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Juliane Krueger Fister, Graduate Student
Authors: Juliane Krueger Fister, Matthew Fister, W. Lee, Troy Hackett, Ph.D.,
Mark Wallace, Ph.D.
Lab P.I. or Faculty Mentor: Mark Wallace, Ph.D.
Department or Program: Neuroscience Graduate Program
Processing converging sensory information from various sensory modalities is a critical
feature of the central nervous system. Traditionally, multisensory processes have been
studied in the cat superior colliculus (SC), a multisensory midbrain structure crucial for
orientation behavior. Recent work has focused on cortical sites of multisensory
integration. In the cat, the anterior ectosylvian sulcus (AES) is such a multisensory
cortical structure. Prior studies established the anatomical connections from and to the
cat SC but much less data is available detailing functional connectivity of the AES.
Briefly, the AES contains three primary sensory domains (AEV, FAES, SIV), along with a
concentration of multisensory neurons at their bordering regions. The AES is
surrounded by areas that have auditory (AII, AAF), somatosensory (SIV, SII), and
multisensory (Ig, AS) properties. The current study sought to identify connectivity
patterns between AES and its surrounding areas in the cat model. A number of tracer
injections were placed into target regions guided by physiological recordings. In case 1,
injections were made in AII and medial to AII within the AES, in a zone responsive to all
three modalities. Labeled cells were found primarily in areas AII, Te, 35/36, and ventral
FAES. Additionally, the AES injection also labeled cells in ALLS. In case 2, injections
targeted AS and Ig. Besides the areas labeled in case 1, cells were labeled throughout the
AEV, SIV, and FAES. In thalamus, labeled cells in all cases were concentrated in the
multisensory nuclei medial and dorsal to the MGB. These preliminary data indicate that
the areas surrounding AES are highly interconnected with the three divisions of AES and
with multisensory thalamic nuclei. An interesting caveat is that weights of connections
may vary systematically in that they may significantly shape convergence patterns. Such
specific arrangements most likely impact the construction of multisensory
representations within the AES and thus may manipulate perception and behavior.
Keywords: multisensory, animal models, anterior ectosylvian sulcus
107. Effects of Preference and Strategy on Learning an
Artificial Script
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Jessica Wise, Undergraduate Student
Authors: Jessica Wise, Yuliya Yoncheva, Ph.D., Bruce McCandliss, Ph.D.
Lab P.I. or Faculty Mentor: Bruce McCandliss, Ph.D.
Department or Program: Psychology and Human Development
When learning to read, it is important to understand letter-sound mappings in order to
read new words. However, during early learning it may be easier for some children to
simply memorize each new word they come across. Previous research has shown that
some children have a preference for one of these two types of reading strategies. Some
children rely on letter to sound mappings (a grapheme-phoneme strategy) while some
match an entire written word with a spoken word (a whole-word strategy). These
preferences may play an important role during the early learning process. In order to
look at the effects of preference on learning in a controlled study, adult subjects were
trained to match English words with novel symbols from an artificial orthography. These
symbols could be broken into smaller letter parts, but could also be viewed as a whole.
Subjects took part in a two day study in which they learned two lists of words each day.
On one list, subjects were instructed to learn using the grapheme-phoneme strategy. On
the second list, subjects were instructed to use the whole-word strategy. It was
hypothesized that preference learners would perform best when words were learned
using their preferred strategy. Additionally, grapheme-phoneme preference learners
would be better at applying their letter knowledge to novel words than whole-word
preference learners, despite equal amounts of training. Results showed that all subjects
regardless of preference performed better on words learned using the whole-word
strategy. However, whole-word preference subjects achieved the highest accuracy of any
group on the whole words on Day 1. Lastly, grapheme-phoneme preference subjects did
perform better on tests of novel words compared to the whole-word preference subjects
on both days. These findings of differential performance based on preference lend
support to the idea that some struggling readers rely exclusively on whole-word strategy,
which leads to difficulty transferring their letter knowledge to new words.
Keywords: reading, artificial orthography, learning
108. Expression of Mutant Huntingtin Increases Arginase
Activity in Mouse Striatum But Decreases Its Susceptibility
to Manganese Exposure
Cellular and Molecular Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Michal Wegrzynowicz, Ph.D., Postdoctoral Fellow
Authors: Michal Wegrzynowicz, Ph.D., Hunter Holt, Aaron Bowman, Ph.D.
Lab P.I. or Faculty Mentor: Aaron Bowman, Ph.D.
Department or Program: Neurology
Huntington disease (HD), a neurodegenerative disorder principally affecting the
striatum, is caused by mutation in the huntingtin (Htt) gene, but severity of the disease
may be strongly influenced by unidentified environmental factors. We have reported a
gene-environment interaction wherein expression of mutant (mt) HTT impairs striatal
manganese (Mn) accumulation. We hypothesize that mtHTT expression may alter
cellular markers of Mn toxicity.
When testing potential markers we found that basal activity of the Mn-dependent
enzyme, arginase, is elevated in the homogenates of striata from mtHTT-expressing mice
(YAC128Q) comparing to wild-type (wt) littermates. Additionally, we observed that in
vivo exposure to Mn (three 50 mg/kg MnCl2 subcutaneous injections over one week)
strongly elevates enzyme activity in striatal extracts, however this effect is less
pronounced in mutant mice. Cortical activity was lower than striatal, and no effect of
genotype was found. In vitro supplementation of vehicle-exposed mice striatum
homogenates with 2 μM Mn (a concentration exceeding the values measured in the
homogenates from animals exposed to Mn in vivo) was much less effective in arginase
activation than subcutaneous exposure in vivo. We conclude that increased activity of
arginase, an enzyme known to be neuroprotective, may be a compensatory response to
mtHTT cytotoxicity in the striatum. Impaired activation of striatal arginase by Mn
administered in vivo in YAC128Q mice is probably due to a mtHTT-induced deficit of Mn
accumulation. Interestingly, the effect of Mn is most likely only partially mediated by
increased availability of Mn, a cofactor of arginase. Inability of in vitro added Mn to
replicate the effects of in vivo exposure suggests that Mn may induce some cellular
processes contributing in the activation of arginase.
Support: NIH ES016931
Keywords: Huntington’s disease, manganese, arginase, gene-environment interaction
109. High-Frequency EEG Correlates of Rhythmic Attending
in Song Perception
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Reyna Gordon, Ph.D., Postdoctoral Fellow
Authors: Reyna Gordon, Ph.D., Edward Large
Lab P.I. or Faculty Mentor: Alexandra Key, Ph.D.
Department or Program: Vanderbilt Kennedy Center
Language and music each have their own metrical structures, but in song these rhythmic
patterns are unified to form one prosodic realization. The present study was designed to
explore the idea that well-aligned textsettings, in which the strong syllables occur on
strong beats, capture listeners’ attention and help them to better understand song lyrics.
EEG was recorded while participants listened to well-aligned and misaligned sung
sentences and performed a lexical decision task on subsequently presented visual
targets. Results showed that induced beta and evoked gamma synchronization were
modulated differently for well-aligned and misaligned syllables, and that task
performance was adversely affected when visual targets followed misaligned sentences.
These findings suggest that alignment of linguistic stress and musical meter in song
enhance beat tracking and linguistic segmentation by entraining periodic neural
oscillations to the stimulus.
Keywords: EEG, rhythm, song perception, music, prosody
110. Retinotopic Evidence for Dorsal V3 in Galagos
Systems Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Reuben Fan, Graduate Student
Authors: Reuben Fan, M. Baldwin, W. Jermakowicz, Vivien Casagrande, Ph.D.,
Jon Kaas, Ph.D., Anna Roe, Ph.D.
Lab P.I. or Faculty Mentor: Vivien Casagrande, Ph.D., Jon Kaas, Ph.D., Anna
Roe, Ph.D.
Department or Program: Neuroscience Graduate Program
There are lingering questions regarding the representation of cortex immediately
anterior to dorsal V2 in primates. One proposal suggests all primates have a V3 that
exhibits a reflected retinotopy across the V2/V3 border. In a manner similar to areas V1
and V2, the inferior and superior visual fields are represented in dorsal and ventral
cortex respectively. Thus, this proposal predicts that the region of cortex immediately
anterior to the dorsal half of V2 represents the inferior visual field. This view of V3 is
supported by anatomical tracer studies (in Old World, New World, and prosimian
primates) and optical imaging evidence (in owl monkeys). However, there exists some
evidence, in New World and prosimian primates, suggesting that cortex directly anterior
to dorsal V2 is the dorsomedial area (DM) representing both the superior and inferior
visual fields. These studies imply that V3 is not an area common to all primate species.
To resolve this controversy, we used intrinsic signal optical imaging and
electrophysiological methods to examine the retinotopic organization of the region
anterior to V2 in anesthetized galagos (Otolemur garnetti), which are prosiman
primates. Using bars and spots, we mapped the representation of the horizontal and
vertical meridian anterior to V2. With these methods, we found no evidence of a superior
visual field representation directly anterior to dorsal V2. Therefore our data are more
consistent with the proposal that this is the dorsal division of V3 and less consistent with
it being DM. Although it is possible that weak optical signals were not detected or that
specific primates are distinct from the majority of primates, we argue that, since V3 is
present in several species of Old World, New World, and prosimian primates, it is likely
to be common across all primate species.
Keywords: V3, extrastriate, retinotopy, galago
111. Open board
112. Cognitive Impairment Due to Combined Dopaminergic
and Cholinergic Depletion: A Novel Mouse Model of
Parkinson’s Disease Dementia
Systems Neuroscience (Session 2: 12:45-1:45 p.m.)
Presenter: Lilia Zurkovsky, Ph.D., Postdoctoral Fellow
Authors: Lilia Zurkovsky, Ph.D., Evgeny Bychkov, Elviche Lenou, Randy Blakely,
Ph.D., Eugenia Gurevich, Ph.D.
Lab P.I. or Faculty Mentor: Eugenia Gurevich, Ph.D.
Department or Program: Pharmacology
A subset of patients with Parkinson’s Disease also acquires a debilitating dementia
characterized by severe cognitive impairments (i.e. Parkinson’s Disease Dementia; PDD).
The understanding of pathological mechanisms and development of effective therapies
are handicapped by absence of animal models for PDD. Importantly, PDD brains show
extensive cholinergic loss, additionally to dopamine (DA)-depletion. We used a mutant
mouse model to directly test whether combined cholinergic-dopaminergic depletion
leads to a cognitive profile resembling PDD. Mice carrying heterozygous deletion of the
high-affinity, hemicholinium-3 sensitive choline transporter (CHTHET) show reduced
levels of acetylcholine throughout the brain. CHTHET and wild-type (WT) littermates
received bilateral DA-depletion via intra-striatal infusion of 6-hydroxydopamine (6OHDA) or vehicle. Executive functioning was examined using attention set-shifting:
Mice were trained to dig in scented media to measure abilities to self-generate a
cognitive plan, alter that plan, and create a set. Visual-spatial recognition evaluated
memory using spatial and object recognition tests. Retention intervals of 5 minutes and
24 hours were employed. For the 24-hour retention period, effects of immediate posttraining injections of the acetylcholinesterase inhibitor, physostigmine (i.p. 0.05 mg/kg),
were measured. Data showed impaired attention set-shifting, specifically ability to
create a set, in WT-6OHDA and CHTHET-vehicle that was even greater in the CHTHET6OHDA group, compared to WT-vehicle. The spatial recognition test with 24-hour delay
showed no group differences. Importantly, the object recognition test showed impaired
memory only in the CHTHET-6OHDA group, an impairment blocked by physostigmine
treatment. These data provide direct evidence for a critical role of cholinergic depletion
in PDD-related cognitive impairments that are exacerbated by dopaminergic loss. DAdepleted CHTHET mice may, therefore, represent a valid animal model of PDD.
Keywords: Parkinson’s disease, dementia, acetylcholine, dopamine, executive function, memory,
physostigmine, animal models
113. Early Maternal Interactions Shape Life-Long
Sociability, Fear Responses, and Anxiety-Related
Behaviors, But Do Not Influence Spatial and Learned
Memory
Clinical, Behavioral, and Intervention Research
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Melinda Arnett, Ph.D., Postdoctoral Fellow
Authors: Melinda Arnett, Ph.D., Jane Hettinger, Maggie Pan, Louis Muglia, M.D.,
Ph.D.
Lab P.I. or Faculty Mentor: Louis Muglia, M.D., Ph.D.
Department or Program: Pediatrics
Early-life stress (ELS) can lead to long-term changes in the stress response system
increasing the risk for development of psychiatric disorders in later life. We
hypothesize that ELS produces heightened levels of anxiety and fear-related
behaviors with corresponding deficits in sociability and spatial and learned
memory in adulthood.
The maternal separation (MS) paradigm was implemented to model ELS. C57BL/6J
mice underwent MS 3 hours/daily from postnatal (PN) day 1 - PN14 and were weaned at
PN29. Control litters were undisturbed until weaning at PN21. An additional control
group, weaned at PN29 (cntl-PN29), was included in the study. In adulthood, we
measured levels of anxiety, sociability, spatial and learned memory and conditioned fear
behaviors in control, cntl-PN29 and MS male mice.
The elevated-zero maze revealed no significant differences between MS (n = 13) and
control (n = 13) mice in the number of entries, or time spent, in the open (P = 0.30, P =
0.59) or closed (P = 0.23, P = 0.41) arms, respectively. Cntl-PN29 mice (n = 13) spent
significantly less time in the open arms compared to MS (P = 0.0001) and control (P =
0.03) mice. The open-field task detected significant differences between MS and cntlPN29 mice in the total time spent (P = 0.03) and distance traveled (P = 0.01) in the
center zone. Conditioned fear studies revealed that MS mice exhibit a significant
decrease in freezing behavior in the presence of the auditory cue compared to control
mice (P = 0.03) and cntl-PN29 mice (P = 0.007). In the direct social interaction task,
MS mice displayed significantly more active social behaviors (P = 0.003) compared to
control mice. Finally, the Morris water maze task showed no significant differences
between MS (n = 9) and control (n = 8) mice in the number of entries (P = 0.62, P =
0.98) or time spent (P = 0.92, P = 0.50) in the platform or target zones, respectively.
These data suggest that ELS provides an enduring resilience to the development of
anxiety and fear-related behaviors, increases sociability and produces no deficits in
learning or spatial memory.
Keywords: stress, anxiety, conditioned fear, social interaction, spatial and learned memory
114. RNA Editing of Tryptophan Hydroxylase 2 Transcripts:
Fact or Fiction?
Cellular and Molecular Neuroscience
(Session 1: 11:45 a.m.-12:45 p.m.)
Presenter: Randi Ulbricht, Ph.D., Postdoctoral Fellow
Authors: Randi Ulbricht, Ph.D., Ronald Emeson, Ph.D.
Lab P.I. or Faculty Mentor: Ronald Emeson, Ph.D.
Department or Program: Pharmacology, Center for Molecular Neuroscience
Tryptophan hydroxylase (TPH) is responsible for the rate-limiting catalytic step in
serotonin biosynthesis. Two TPH genes are encoded in the mammalian genome, TPH1
and TPH2. TPH2 is the main contributor to serotonin synthesis in the brain and its
functional polymorphisms have been linked to suicide, attention deficit/hyperactivity
disorder and major depression. Grohmann et al (2010) identified multiple TPH2 protein
isoforms in human brain tissue resulting from post-transcriptional processing events.
Two possible TPH2 mRNA isoforms are created as a result of alternative splicing (TPH2a
and TPH2b). Additionally, four different classes of RNA editing events change up to
eight nucleotides in the transcript, seven of these editing events occur within the coding
region. Editing at four of these sites leads to changes in amino acid sequence, while one
editing event creates a premature stop codon and thus, a null allele. Functional analyses
of proteins encoded by edited TPH2 mRNA isoforms suggest that editing significantly
decreases catalytic activity (Grohmann et al 2010); thus mRNA editing may represent a
post-transcriptional mechanism to modulate serotonin biosynthesis and availability.
Based on this published data, we hypothesized that TPH2 mRNA processing is a
dynamic regulator of TPH2 expression and protein function.
We began our own studies by analyzing TPH2 mRNA processing in rodent model
systems with the expectation that the identification of analogous editing events will allow
for an expanded analysis functional isoforms these species. While we detected no
alternative splicing in human or mouse, we were able to detect an alternative splicing
isoform from rat whole brain RNA. Rather than an alternative 5’ splice site to include an
extra 6 nucleotides in exon 3, as the previous study detected (Grohmann et al 2010), we
detected an alternative 3’ splice to include an extra three nucleotides in exon 4. Our
analyses of TPH2 transcripts from mouse, rat, human neuronally-derived cell culture
systems and human brain RNA show no indication of RNA editing. In the future, we will
use a more sensitive high-throughput technique to detect and/or quantify RNA editing
or alternative splicing that our current techniques may overlook.
Keywords: RNA editing, tryptophan hydroxylase, serotonin
115. “No Broccoli, More Cake!”: Verbalizations and
Psychological States in Mothers of Children with
Prader-Willi Syndrome
Clinical, Behavioral, and Intervention Research
(Session 2: 12:45-1:45 p.m.)
Presenter: Grace Kulbaba, Vanderbilt Kennedy Center Staff
Authors: Nancy Miodrag, Ph.D., T. Frances Ulman, Grace Kulbaba, Carolyn
Shivers, Elisabeth Dykens, Ph.D.
Lab P.I. or Faculty Mentor: Elisabeth Dykens, Ph.D.
Department or Program: Psychology
Individuals with Prader-Willi syndrome (PWS) exhibit a unique behavioral phenotype
that includes a tremendous preoccupation, drive, and overconsumption of food which
can lead to life-threatening health problems (Cassidy & Driscoll, 2009). Such food issues
persist across the lifespan and can cause significant stress for parents (Goldberg, Garrett,
Van Riper, & Warzak, 2002). To date, researchers relied on self-reports to document
psychological states in parenting children with PWS (Abbeduto et al., 2004). This study
builds on our understanding of families of children with PWS by observing mother-child
interactions about food and its association to self-reported maternal well-being and the
PWS behavioral phenotype.
Data were drawn from an ongoing study examining developmental trajectories in adults
and children with PWS. Children (N = 45; 23 males, 22 females) and their mothers were
videotaped during a 5-minute hypothetical ‘create a birthday party menu’ task in which
negative and positive maternal verbalizations were coded. Mothers also completed the
Parenting Stress Index (PSI-SF), Beck Depression Inventory (BDI), Satisfaction with Life
Scale (SWLS), Coping Inventory (COPE), Yale-Brown Obsessive-Compulsive Scale (YBOCS), Hyperphagia scale, and Child Behavior Checklist (CBCL). Child IQ was
established using the Kaufman Brief Intelligence Test (K-BIT-2).
Bivariate correlations between mother verbalizations and psychological states revealed
significant correlations between PSI distress and humor, PSI life stressors and negative
verbalizations, greater BDI physical symptoms of depression and: more direction, less
humor, and less positive social laughter. Regarding child behaviors, correlations were
found between increased humor and less delinquency, more praise and greater social
competence. Humor also correlated to less intrusive obsessive-compulsive behaviors.
Positive social laughter and negative maternal verbalizations were significantly related to
more food items children selected.
Findings suggest that positive and negative maternal responses to their child’s food
choices are significantly related to psychological well-being and the child’s problem
behaviors. Parents that weave positive interactions into daily life may experience a buffer
against psychological difficulties and maladaptive child behaviors. Our findings
underscore how important positive interactions are in managing a highly charged issue
for many families of children with PWS.
Keywords: Prader-Willi syndrome, mother-child interaction, humor, stress
Index of Abstracts by Presenter
Aboud, 54, 99
Adkins, 11
Allison, 2
Anderson, 5
Armour, 85
Arnett, 113
Avery, 67
Barquero, 66
Barrett, 1
Baucum, 95
Bichell, 60
Borgschulte, 72
Brock, 87
Bronson, 80
Chakraborty, 76
Clauss, 16
Clay, 82
Conrad, 39
Corbett, 14, 19
Dang, 46
Dankner, 65
Downs, 53
Doydum, 83
Dunn, 70
Dykens, 77
Eckstrand, 102
Edery Clark, 103
Edmiston, 31
Educational Neuroscience Initiative
Consortium, 8
Erreger, 84
Essex, 96
Fan, 90
Fan, R., 110
Fisher, 81
Fister, 106
Foss-Feig, 79
Fyfe, 34
Geng, 49
Ghose, 12
Goodman, 27
Gordon, 109
Grier, 52
Griffin, 92
Gu, 100
Hammock, 29
Hardaway, 91
Hawkins, 37
Henderson, 3
Henninger, 58
Hubbard, 20
Jalan-Sakrikar, 48
Jones, 94
Joosten, 9
Jorge, 62
Kale, 40
Key, 7
Kliman, 47
Klug, 56
Korade, 18
Koran, 86
Kraemer, 78
Kulbaba, 115
Kwakye, G., 59
Kwakye, L., 45
Lambert, 10
Laryea, 41
Ledford, 23
Lense, 30
Lieberman, 38
Limpert, 104
Lin, 28
Litt, 17
Majumdar, 93
Martin, 36
Matthews, 4
Mayer, 98
McIntosh, 101
Moneta, 15
Muller, 73
O’Brien, 75
Peterman, 42
Potts, 51
Pryweller, 55, 77
Rentmeester, 63
Restrepo, 74
Robinson, 89
Rosemergy, 6
Sakrikar, 33
Sawyer, 71
Scheib, 61
Schmidt, 24
Seay, 64
Shirey-Rice, 88
Shivers, 50
Siller, 32
Simmons, 105
Starkey, 44
Thakkar, 26
Tidball, 54
Ulbricht, 114
Varney, 21
Vazquez, 25
Viarouge, 35
Vollbrecht, 43
Wegrzynowicz, 108
Werfel, 22
Wills, 97
Wise, 107
Wright, 69
Xu, 13
Yoncheva, 57
Zurkovsky, 112
Index of Abstracts by Lab P.I. or Faculty Mentor
Anderson, 90
Aschner, 76
Avison, 102
Blackford, 16, 64, 67, 69
Blakely, 33, 73, 91
Bowman, 17, 27, 54, 59, 60, 99, 108
Broadie, 32
Carneiro, 21
Carter, 46, 61, 78, 104
Casagrande, 110
Cascio, 79
Colbran, 48, 56, 95
Compas, 51, 70, 89
Compton, 90
Conture, 94, 103
Corbett, 14, 19
Cowan, 102
Cutting, 66, 90
Delpire, 97
Deutch, 43
Dykens, 30, 65, 115
Emeson, 114
Ess, 17, 27, 54, 60, 85, 99
Fuchs, D., 90
Fuchs, L., 90
Galli, 84
Garber, 53, 72
George, 62
Gore, 90
Gurevich, 112
Haas, 52, 60
Hackett, 75
Hahn, 88
Hammock, 29
Heckers, 82
Hodapp, 50, 92
Kaas, 110
Kearney, 37
Key, 109
Konradi, 80, 82
Korade, 13, 18, 47
Lagrange, 52
Maitre, 105
McCandliss, 15, 20, 35, 44, 49, 57, 83,
100, 107
McLaughlin, 36, 40
Mirnics, 24
Muglia, 41, 113
Neely, 17, 27, 54, 60, 99
Park, 26, 42, 98, 101
Porter, 13, 18, 47
Rimrodt, 66
Rittle-Johnson, 34
Roe, 87, 110
Saylor, 25
Schuele, 22, 81
Shelton, 13
Sutcliffe, 73
Taylor, 50, 58
Tharpe, 63
Thornton-Wells, 55, 67, 69, 74, 77, 86
Veenstra-VanderWeele, 73
Walden, 94, 103
Wallace, 12, 45, 106
Webb, 28, 93
Winder, 39, 56, 97
Wolery, 23
Yoder, 38
Zald, 96
Index of VKC Core or University Services Posters
Cell Imaging Shared Resource, 4
Communication and Dissemination Services, 6
Community Engaged Research Core, 9
Educational Neuroscience Initiative Consortium, 8
Mouse Neurobehavioral Core, 2
Neuroimaging Core, 5
Psychophysiology Services EEG/ERP Laboratory, 7
Rat Core of the Laboratory for Neurobehavior, 1
Research Participant Recruitment and Assessment Services, 3
Sleep Disorders Center, 11
Statistics and Methodology Core, 10
Index of Keywords
7-dehydrocholesterol, 18
7-dehydrocholesterol oxidation, 13
acetylcholine, 112
actin, 28
addiction, 97
ADHD, 33, 88, 102
adolescents, 80
adult outcome, 58
affect, 42, 101
aging, 95
Akt, 93
alerting, 49
alpha actinin, 48
Alzheimer's disease, 74, 86
AMPA receptors, 28, 93
amygdala, 16, 64, 67, 80
Angelman syndrome, 52, 60
animal models, 24, 29, 37, 73, 106, 112
anterior ectosylvian sulcus, 106
antioxidant, 13
anxiety, 29, 30, 69, 80, 97, 113
APPL1, 93
arginase, 108
arousal, 30
artificial orthography, 107
assessment, 79, 103
attitudes, 63, 103
auditory, 75
autism spectrum disorders, 14, 19, 23,
32, 38, 58, 65, 73, 79
BDNF, 78
behavior, 24
behavioral screening, 91
binge, 80
bipolar disorder, 82
BNST, 97
brain atrophy, 74
BRG1, 104
CaMKII, 48, 56
cancer, 70
cerebral asymmetry, 71
cerebral palsy, 106
characterization, 27
child abuse/neglect, 31
chimpanzee, 71
cholesterol, 18, 47
chromatin remodeling, 104
cilia, 85
circadian clock circuit, 32
cocaine, 39, 80
complex syntax, 81
computers, 25
concrete manipulatives, 34
conditioned fear, 113
connectivity, 90
constraint-induced movement therapy,
106
coping, 51, 70, 89
copy number variation, 69
corticotropin-releasing hormone, 41
cortisol, 14, 19, 30
C-terminus of HSC70 interacting
protein, 40
deep brain stimulation, 98
dementia, 112
dendritic spines, 28, 43, 93, 95
depression, 51, 53, 72
diabetes, 84
diffusion tensor imaging, 35, 67, 90
dopamine, 43, 84, 91, 112
dopamine 2 receptor, 91
dopamine transporter, 33
Down syndrome, 23
drug discovery, 60
E3 ubiquitin ligase, 40
early intervention, 38
early literacy, 22
EEG, 109
electrical microstimulation, 87
elementary school, 44
emotion regulation, 89
engulfment, 46, 61
environmental metals, 99
epilepsy, 37, 52, 62
epistasis, 74
ERP, 45, 57
ethanol, 97
executive attention, 49
executive function, 83, 112
experience-dependent development, 29
extrastriate, 110
face processing, 71
families, 50, 72
fMRI, 20, 26, 66
forward genetics, 91
frontal cortex, 20, 98
Fura2, 59
GABA receptors, 52
galago, 110
gammasecretase, 78
GEFS, 37
gender, 53, 72
gene expression, 13, 24
gene-environment interaction, 54, 99,
108
genetics, 37, 86
GLP1, 84
glucose, 82
GluN2B, 56, 97
glutamate, 43
guilt, 50
GULP, 46, 61
habit learning, 56
hearing aids, 63
hearing loss, 22, 63
hemiparetic CP, 106
high-throughput assay, 59
hippocampus, 16, 64
hIPSC, 17
HSP 70, 40
humor, 115
Huntington's disease, 59, 108
imaging, 47
imaging genetics, 86
imitation, 26
immunocytochemistry, 17
inclusion, 92
individual differences, 96
induced pluripotent stem cells, 54
inhibited temperament, 64
integration, 12
integrin, 21
intellectual quotient, 55
interneurons, 24
intervention, 22
ion channels, 37
iPSC, 27, 60
ischemic injury, 40
Jedi-1, 46, 61
Kcnv2, 62
KiddyCAT, 103
kidney, 85
knowledge state attribution, 25
Kv 82, 62
language experience, 100
language learning, 57
late positive complexity, 49
learning, 34, 107
learning by teaching, 25
linear regression, 74
long-term potentiation, 39
manganese, 59, 108
manganism, 76
mathematics, 15, 34
medial geniculate body, 75
MEGF10, 46, 61
memory, 30, 112
metal transport, 59, 76
minicolumn, 71
mirror neurons, 26
mitochondria, 82
mother-child interaction, 115
MRI, 31
mTOR, 27, 85
multisensory, 12, 106
multisensory integration, 45
music, 109
mutation, 88
myelin, 104
N170 lateralization, 57
narrative, 94
near-infrared spectroscopy, 98
negative cognitive style, 51
neuralization, 17
neurodegenerative disease, 76
neuroimaging, 55, 74, 86, 102
neuromuscular junction, 32
neuron development, 99
neuronal differentiation, 60
neuroprotection, 36
neurotoxicity, 54, 76
neurotrophin, 78
NFkB, 104
NGF, 78
nitric oxide, 84
NMDA receptors, 48
non-native phonetic representations, 100
nonverbal, 101
norepinephrine, 88
numeracy, 44
numerical cognition, 20, 35
optical imaging of intrinsic signals, 87
orexin, 39
orthostatic intolerance, 88
oxidative stress, 36
oxysterol, 13, 18
p66Shc, 36
p75, 78
parent health, 65
parietal cortex, 20
parkin, 76
Parkinson's disease, 54, 95, 98, 112
patient-specific toxin screen, 99
pediatric leukemia, 89
phonological awareness, 22
physiology, 94
physostigmine, 112
play, 14, 19, 38
positive affect, 70
postsecondary education, 92
post-synaptic density, 28
Prader-Willi syndrome, 65, 115
prefrontal cortex, 16, 43, 67
prenatal alcohol exposure, 102
prosody, 109
protective risk management, 96
quantitation, 47
rapamycin, 27
reactive oxygen species, 36
reading, 35, 66, 107
reading ability, 90
reading acquisition, 57
receptive field, 12
redox signaling, 36
resilience, 70
respiratory sinus arrhythmia, 94
retinotopy, 110
rhythm, 109
risk taking, 96
RJA, 38
RNA editing, 114
schizophrenia, 24, 26, 42, 43, 101
Schwann cell, 104
segmentation, 64
selective attention, 57
sensory, 73, 79
sensory modulation, 77
sentence comprehension, 66
serotonin, 29, 73, 114
serotonin transporter, 21, 73
siblings, 50
signaling, 48, 95
silent synapses, 56
SLOS, 47
small group instruction, 23
small molecules, 17
Smith-Lemli-Opitz syndrome, 13, 18
social cognition, 26, 42, 101
social development, 63
social interaction, 14, 19, 23, 113
social trait, 101
song perception, 109
spatial and learned memory, 113
spatiotemporal dynamics, 12
spectrometry, 47
speech perception, 100
stem cells, 17, 60, 99
stereotaxic injections, 41
stress, 14, 19, 21, 29, 41, 65, 113, 115
stria terminalis, bed nucleus, 39
striatum, 56, 84
stuttering, 94, 103
superior colliculus, 12
symbolic understanding, 34
synapse formation, 93
synaptic plasticity, 48
synaptic transmission, 28
tactile, 79
teacher talk, 81
temperament, 16, 69
temporal processing, 45
tetracycline-inducible system, 41
tonotopy, 75
transition, 58
translational regulator, 32
transporters, 88, 91
tryptophan hydroxylase, 114
Tuberous Sclerosis, 27, 54, 85
V3, 110
vagal tone, 94
volumetry, 64
voxel-based morphometry, 16, 102
Williams syndrome, 30, 55, 65, 67, 69,
77
working memory, 98
yohimbine, 39