UCL NEUROSCIENCE DOMAIN
UCL 2015 Neuroscience
Symposium Poster
Abstract Booklet
www.ucl.ac.uk/research/domains/neuroscience
UCL NEUROSCIENCE DOMAIN
Table of Contents
Laboratory Posters
(L1 – 25, Jeffery Hall)
Developmental Neuroscience Posters
(1 – 15, Jeffery Hall)
Neural Excitability, Synapses and Glia: Cellular
Mechanisms Posters
(16 – 36, Elvin Hall)
Novel Methods, Resources and Technology
Development Posters
(37 – 45, Elvin Hall)
Cognition and Behaviour
(46 – 64, Elvin Hall)
Homeostatic and Neuroendocrine Systems
Posters
(65, Elvin Hall)
Sensory and Motor Systems Posters
(66 – 83, Elvin Hall)
Disorders of the Nervous System
(84 – 135, Drama Studio)
Other Posters
(136 – 138, Drama Studio)
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18
26
37
43
53
54
63
92
Laboratory Posters | Jeffery Hall
[Lab PI and affiliation. Presenting author listed if not the PI.]
L1. MARCO BEATO – UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
Joshua Foster
POSTER TITLE
Synaptic circuits and neuronal connectivity in the lumbar spinal cord
AUTHORS
Marco Beato's lab
ABSTRACT
It has been known since the early part of the 20th century that the spinal cord contains many
of the neuronal circuits necessary for the generation of motor behaviours. Our overarching
aim is to understand the pattern of connectivity and synaptic properties of last order
premotor interneurons, that are essential in shaping the activity pattern of motoneurons and
therefore the pattern of muscle contraction.
We optimized the technique for obtaining electrophysiological recordings of synaptically
connected motoneurons and premotor interneurons in spinal cord slices and devised a novel
technique for determining the quantal parameters at individual synapses using Bayesian
modelling. Using these methods we have obtained the first recordings and characterization
of the reciprocal connections between identified Renshaw cells and motoneurons.
We are currently taking advantage of the introduction of novel single step transynaptic
tracers to characterize a wider range of premotor interneurons in both slices and en bloc
spinal cord preparations
L2. NEIL BURGESS - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Computational modelling of the neural mechanisms of spatial cognition
AUTHORS
Burgess N
ABSTRACT
Much is known about the neural coding of spatial location and orientation in the hippocampal
formation (place cells, head direction cells, grid cells and boundary cells). Starting from this
basis we develop neural-level models of the systems supporting spatial navigation, episodic
memory and imagery. These models are used to make predictions at the level of behaviour
and neural activity.
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* Episodic retrieval and imagery uses attractor dynamics in MTL to drive pattern completion
and (re)activation of allocentric representations of the scene of an event (following Burgess
et al. 2001; Byrne et al. 2007) to which objects are now added. Imagery reflects creation of
an egocentric representation in medial parietal and retrosplenial areas making use of 'gain
field' and head direction cells. The extended model can remember, imagine and navigate to
the locations of specific objects.
* Interplay between hippocampal and striatal systems is simulated in the context of learning
to navigate to a specific location over multiple trials. Object locations are learn as incidental
Hebbian associations between hippocampal place cells and object attributes, and as
reinforced sensory state-action sequences in striatum. Arbitration between which system
controls behaviour reflects the relative slopes of their value functions.
L3. NEIL BURGESS - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
Daniel Bush
POSTER TITLE
Experimental investigation of the neural mechanisms of spatial cognition
AUTHORS
Space and Memory Group, UCL Institute of Cognitive Neuroscience
ABSTRACT
Learning the location of task-relevant objects and potential dangers within an environment is
a crucial adaptive behaviour. Here, we present the results of two human spatial memory
studies that have recently been completed in the ICN Space and Memory lab. Firstly, we
have analysed intracranial EEG recordings from pre-surgical epilepsy patients at the
National Hospital of Neurology and Neurosurgery performing a virtual reality spatial memory
task that is analogous to the Morris water maze. We identify a movement-onset related
increase in theta (6-10Hz) band oscillatory power and show that the magnitude of this theta
power increase correlates with spatial memory performance. Secondly, combining fear
learning paradigms with virtual reality, we have investigated the manner in which individuals
learn about areas within a single environment that predict safety or danger. We present fMRI
data showing location specific fear learning in humans and describe how the amygdala,
hippocampus and mPFC contribute to learning about the emotional properties of an
environment. In summary, the results of these studies illustrate the contribution of medial
temporal and frontal lobe structures to efficient human spatial memory function.
L4. FRANCESCA CACUCCI – UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY
& PHARMACOLOGY
Laurenz Muessig
POSTER TITLE
Space in the brain – building representations of the world from experience
AUTHORS
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Francesca Cacucci's lab
ABSTRACT
How does the brain represent space? Place cells were first discovered in the rodent
hippocampus in the 1970s at UCL, and are thought to form a cognitive representation of
space. Ever since the hippocampal formation has been extensively studied by many
laboratories across the world and the Cacucci lab is part of this community. Our interests
focus on the following questions: How does the brain’s representation of space emerge
during post-natal development? How do external inputs influence this representation? And
how do different brain areas interact to form a coherent representation of external space? To
address these questions, we are currently collaborating with several labs at UCL (M. Beato,
N. Burgess, T. Keck, P. Salinas, T. Wills) as well as M. Tripodi (Cambridge) and C. Lever
(Durham), bringing together various techniques including in vivo electrophysiology, viral
tracing, optogenetics and computational analysis.
Current projects include extracellular recordings from the hippocampal formation (place
cells, boundary responsive cells), entorhinal cortex (grid cells) and thalamus (head direction
cells) of rat pups, adult mice and rats, in freely moving animals and in virtual reality
environments. Additionally we are also studying the functional connectivity between these
brain areas by using modified rabies virus to trace connections.
L5. MARIA CHAIT - UCL EAR INSTITUTE
POSTER TITLE
How the brain makes sense of sound
AUTHORS
Chait M
ABSTRACT
The many sound-generating sources within the environment add up into one combined
wave-form that enters the ear. In order to make sense of the world, a listener must separate
this input into representations of the difference objects in the scene, determine their location
in space, recognize them, and react appropriately. Our work aims to understand the
processes by which such a representation is created by the brain and how it is maintained the processes by which auditory sensory information is converted into a perceptual
representation of our surrounding environment. Our methodology is based on a combination
of functional brain imaging and psychophysics. By studying how brain responses unfold in
time, we explore how representation that are useful for behavior arise from sensory input
and dissociate automatic, stimulus-driven, processes from those that are affected by the
perceptual state, task and goals of the listener.
Examples of the questions we address in our experiments are: What information about the
statistics of the ongoing sound input does the brain extract and represent? How do listeners
detect the appearance or disappearance of new auditory objects (sound sources) in the
environment? What makes certain events ‘pop-out’ and grab listeners’ attention even when it
is focused elsewhere while the detection of other events requires directed listening? How
does visual input affect how listeners process auditory information? How are listeners able to
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focus attention on one sound in a mixture? Can information about the current focus of
attention be extracted from real-time EEG data for the purpose of ‘steering’ a hearing aid?
L6. JONATHAN CLAYDEN - UCL INSTITUTE OF CHILD HEALTH
POSTER TITLE
Multimodal imaging of brain connectivity and networks
AUTHORS
Clayden J
ABSTRACT
We outline our work using a range of noninvasive in vivo human imaging techniques to
understand structural and functional brain connectivity. Our interests include relating
measures of connectivity, investigating how these links break down in disease, and
understanding population variability. We develop image analysis and modelling methods and
apply them to a range of clinical and nonclinical neuroscience applications, particularly in
children.
L7. ANDREW COPP - UCL INSTITUTE OF CHILD HEALTH
Dianne Gerrelli
POSTER TITLE
Understanding congenital disease through investigations of human embryonic and fetal
development
AUTHORS
Gerrelli D, Santos C, Gold Diaz D, Lisgo S, Lindsay S, Copp AJ
ABSTRACT
The Human Developmental Biology Resource (HDBR www.HDBR.org) is a unique resource
funded by the MRC and Wellcome Trust. It provides human embryonic and foetal tissue for
gene expression studies related to congenital disease, including both birth defects and
inherited metabolic disorders. Use of the material should particularly illuminate
developmental gene expression underlying aspects of functioning that characterise humans
as opposed to lower animals (e.g. higher brain function, language). This research is
essential if we are to introduce new methods for prevention of congenital defects and
develop an improved understanding of “what makes us human”.
The HDBR has ethics approval for the collection, storage and distribution of material
between 4 and 20 weeks post conception. The material can be used to generate cell lines,
stem cells, protein, RNA and DNA. In addition, paraffin wax and frozen sections of embryos
and early foetuses are available for in situ hybridisation and immunohistochemistry. For
users who do not have experience in gene expression analysis the HDBR offers an in-house
gene expression service using in situ hybridisation and/or immunohistochemistry.
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We will highlight data from recent projects that have used our resource to study gene
expression in the human embryonic and foetal brain and spinal cord.
L8. ANDREW COPP - UCL INSTITUTE OF CHILD HEALTH
Chloe Santos
POSTER TITLE
Human developmental biology resource
AUTHORS
Santos C, Gold Diaz D, Gerrelli D, Lisgo S, Lindsay S, Copp AJ
ABSTRACT
The Human Developmental Biology Resource (HDBR) is a unique resource funded by the
MRC and Wellcome Trust. The HDBR provides embryonic and fetal tissue for research
purposes. Here we highlight some of the research areas where our resource has provided
insight into a variety of areas of science using human embryonic tissue. We are licensed as
a tissue bank by the Human Tissue Authority to collect material between 4 and 20 post
conception weeks. Our services can be used to generate cell lines, stem cells, protein, RNA,
cDNA and genomic DNA. We also provide paraffin wax or frozen sections of embryonic and
fetal tissue. Furthermore, gene expression studies (in-situ hybridisation or
immunohistochemistry) can be conducted to your specification.
L9. FRANCES EDWARDS – UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Hippocampal synaptic transmission and plasticity in mouse models of dementia
AUTHORS
Edwards F
ABSTRACT
Primary aim: Understanding alterations in synaptic transmission, plasticity and homeostasis
in mouse models of dementia and in normal ageing; uncovering new treatment targets for
Alzheimer’s disease.
Techniques:
 Electrophysiology; patch clamp and field recording
 Acute brain slices
 Cultures (organotypic and neuones)
 Molecular biology
 Immunohistochemistry
 Confocal microscopy
 Behaviour
Collaborations:
 Genomics (John Hardy)
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


Immunoprecipitation mass-spectrometry (Kaj Blennow, Sweden)
Mouse models GlaxoSmithKline- APP, PSEN1 and TAU transgenics
+ APP KI mice from Saito and Saido
Areas of research:
Alzheimer's disease including:
1. The role of pentraxins in synaptic transmission and their relationship to AD
2. The importance of microglial genetic networks in AD
3. Early synaptic changes in mouse models of AD and prefrontal dementia
4. Plasticity over the lifespan of WT mice and the interaction with AD
5. Overlaps between insulin-like signalling, diabetes and AD
Lab members:
 Senior ARUK Research Fellow: Dr Dervis Salih
 Postdoctoral Research Fellows: Dr Damian Cummings, Dr Marina Yasvoina
 Statistical Consultant: Dr Lion Shahab
 PhD Students: Zelah Joel, Tiffanie Benway, Joshua Paulin, Wenfei Liu
 MSc students: Fabia Moroni, Patricia Pascual Vargas
 Research Assistanst: Rivka Steinberg, Shabinah Ali
Funding: MRC; ARUK; Eisai
L10. KIRSTEN HARVEY - UCL SCHOOL OF PHARMACY
Andrea Wetzel
POSTER TITLE
The role of LRRK2 in cell biological functions
AUTHORS
Harvey K
ABSTRACT
Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2) are a common cause of
Parkinson's disease (PD). This fact makes LRRK2 and LRRK2 signalling components
particularly attractive as therapeutic targets. LRRK2 is a complex protein, containing a
kinase domain, a GTPase domain and multiple protein-protein interaction domains. We
showed that LRRK2 interacts with Wnt signalling components a) in the β-catenin destruction
complex; b) dishevelled proteins; and c) the LRP6 Wnt co-receptor. Furthermore, LRRK2
interacts with components of the cytoskeleton supporting a role of LRRK2 in microtubule
dynamics. Wnt signalling pathways are essential regulators of neuronal development and
have been proposed to be key contributors to the pathogenesis of neurodegenerative
disorders. The importance of Wnt signalling for midbrain dopaminergic neurons during
neuroinflammatory responses in PD animal models has recently been reported. LRRK2 was
also shown to affect Ca2+-dependent responses via the Nuclear factor of activated T-cells
(NFAT), autophagy and mitochondrial function. Increasing our understanding about the role
of LRRK2 in Wnt and Ca2+ signalling might contribute to the development of new PD
treatments.
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L11. POSTER WITHDRAWN
L12. IMRE LENGYEL - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
Molecular and clinical imaging of dementia through the eye
AUTHORS
Lengyel I
ABSTRACT
Alzheimer’s disease (AD) is the commonest neurodegenerative disorder, affecting one half
of all people over the age of 80 years. Costs of AD to European states and carers are
greater than the costs of heart disease, stroke and cancer combined. Several biomarkers of
early disease are available with the current gold-standard being PET studies of amyloid and
tau deposition and brain metabolism, MR imaging of cerebral atrophy and CSF tau sampling.
However such techniques are invasive or require significant patient co-operation and
compliance. Elderly patients are often unable to have a scan because of contraindications.
Furthermore, it is not feasible to undertake serial PET and CSF studies due to restrictions on
radiopharmaceutical dosing and the undesirability of repeated CSF sampling. The
programme in the Lengyel lab, in collaboration with the researchers of dementia, evaluate
eye imaging that overcomes such problems in that it is fast, requiring minimal co-operation
on the part of the patient, cheap in comparison to PET and MRI technology, can be used for
serial sampling and may provide a indirect view of progression of dementia in the brain. In
addition, we us molecular imaging to uncover potential surrogate markers for even more
precise phenotyping in the future.
L13. NICHOLAS LESICA - UCL EAR INSTITUTE
POSTER TITLE
The neural representation of speech
AUTHORS
Lesica N
ABSTRACT
Before we can attempt to understand the neural circuitry that underlies our ability to
communicate, we must first determine what features of brain activity carry important
information about speech. We have examined the resolution and complexity of the neural
representation of speech at two important stages of the auditory pathway by making multitetrode recordings from the midbrain and cortex of gerbils, a commonly used animal model
for studies low-frequency hearing. We found a number of fundamental differences in the
neural code for speech in the inferior colliculus (IC) and primary auditory cortex (A1). In the
IC, spike patterns carry information about speech with sub-millisecond precision and the
variability that is shared between neurons is very small. In A1, population spike patterns
depend strongly on brain state. Activity in synchronized A1 is only weakly modulated by
speech, and spike patterns are unreliable and tightly constrained. In contrast, spike patterns
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in desynchronized A1 are more similar to those in the IC, with high temporal precision and
low shared variability. The differences between the IC and A1 also extend to the coding of
auditory space: in the IC, neurons have broad, homogeneous spatial tuning and encode the
location of speech through variations in overall hemispheric spike rate, while in A1, neurons
with sharp spatial tuning and different preferred locations encode the location of speech
through a series of labeled lines. Taken together, these results suggest that the neural
representation of speech is transformed from IC to A1 and has important implications for
how different auditory cues may be used in the analysis of complex auditory scenes.
L14. JENNIFER LINDEN - UCL EAR INSTITUTE
POSTER TITLE
Neural mechanisms of normal and abnormal central auditory processing
AUTHORS
Linden J
ABSTRACT
Research in the Linden laboratory focuses on questions about the neural mechanisms
underlying normal and abnormal auditory processing, especially in the auditory cortex and
thalamus. Our primary model system is the mouse, and our studies include investigations of
auditory function both in normal mice and in mouse models of human conditions such as
central auditory processing disorder and schizophrenia. Work in the laboratory is
interdisciplinary, involving a combination of electrophysiological, histological, behavioural
and computational approaches to understanding brain function. We further extend the scope
of our research through multiple collaborations with other laboratories, both within and
beyond UCL. Recent research topics highlighted in this poster include: computational and
optogenetic investigations of interneuron function in auditory cortex of awake mice; deficits in
central auditory sensitivity to sound offsets in a mouse model of human developmental
disorder; and abnormalites in parvalbumin-positive interneuron density in auditory cortex of a
mouse model of schizophrenia.
L15. MAIREAD MACSWEENEY - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Visual Communication Research Group
AUTHORS
Macsweeney M
ABSTRACT
We explore the neural basis of language processing in people who are born profoundly deaf.
Using a range of neuroimaging and behavioural methods, our research focuses on sign
language, speechreading and reading of written English.
Exploring the brains of adults who have had very different sensory and language experience
from the norm allows a unique perspective on how experience shapes the brain. For
example, we have shown that parts of auditory cortex can be used to process visual
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information in people who are born deaf. Advances in this field are not only of theoretical
interest, but are likely to also have important practical implications for how we educate deaf
children, since the vast majority of deaf children find it very difficult to learn to read.
Current projects include a randomized controlled study of a speechreading and reading
intervention for young deaf children, several projects using ‘functional transcranial Doppler
ultrasound’ (fTCD) to examine lateralisation of language in hearing and deaf adults and
children, and an infant ‘near infrared spectroscopy’ (NIRS) study of early responses to
spoken and signed language in hearing babies of deaf mothers.
L16. SARA MOLE - MRC LABORATORY FOR MOLECULAR CELL BIOLOGY
POSTER TITLE
The neuronal ceroid lipofuscinoses (Batten disease)
AUTHORS
Mole S
ABSTRACT
The Mole Laboratory is mainly interested in the neuronal ceroid lipofuscinoses (NCL, Batten
disease). These are monogenic inherited neurodegenerative diseases characterised by the
accumulation of autofluorescent lipofuscin-like (age pigment) material in lysosomes, and
neuronal loss. Those affected suffer seizures, visual failure, declining mental and motor
skills, and die prematurely. The age of onset ranges from birth to late in adulthood, mostly
affecting children, and is characteristic for the underlying genetic defect. Thirteen genes
have been identified, and over 400 mutations. We curate the international NCL mutation
database.
We have 4 main research interests: 1) The identification of new NCL genes, and NCL
classification and diagnosis; 2) Understanding the molecular and cellular basis of juvenile
CLN3 disease; 3) Identify new therapeutic targets and drugs for treating CLN3 disease; 4)
Developing gene therapy to treat the visual failure of CLN3 disease. We make extensive use
of systems approaches and the genetic tractability of fission yeast Schizosaccharomyces
pombe to speed aims 2) and 3).
L17. SARA MOLE - MRC LABORATORY FOR MOLECULAR CELL BIOLOGY
Rachel Brown
POSTER TITLE
Fission yeast as a model for juvenile CLN3 disease
AUTHORS
Brown R, Fiadeiro R, Bond M, Rallis C, Marotta D, Vieira M, Bähler J, Mole SE
ABSTRACT
The neuronal ceroid lipofucinoses (NCLs) are the most common form of childhood
neurodegenerative disease. They are characterised by the accumulation of material in the
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lysosomes of most cells, with symptoms including dementia, seizures and blindness, and
premature death. Juvenile CLN3 disease represents the majority of NCL cases, although
the function of the disease gene CLN3 is still unknown.
CLN3 is however highly evolutionary conserved. The fission yeast Schizosaccharomyces
pombe is an ideal system for the study of CLN3 disease, as it contains a single nonessential orthologue of CLN3 (btn1), which evidence suggests shares the same function as
CLN3.
We have used this fission yeast model extensively to study btn1 function, and to highlight
new therapeutic strategies for juvenile CLN3 disease. Using a genome-wide approach, we
have identified a set of core stress-response pathways that appear compromised in yeast
lacking a functional copy of btn1. The genetic and pharmacological attenuation of these
pathways can modulate key disease phenotypes seen in our model, leading to the most
complete rescue of yeast phenotypes achieved to date. This approach, complemented by
work performed in patient cell lines, has also revealed a possible role for ER stress in the
pathogenesis of juvenile CLN3 disease, leading to another pathway that may be a focus for
therapeutic developments.
L18. PAOLA PEDARZANI – UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
Marisol Sampedro Castaneda
POSTER TITLE
Molecular and functional properties of neuronal ion channels and their role in intrinsic
excitability
AUTHORS
Sampedro Castaneda M, Tedoldi A, Howe T, Tebbs-Warner J, Gallasch L, D'Antoni M,
Stocker M, Pedarzani P
ABSTRACT
Our work focuses on the principal cells of the hippocampus, a cortical brain region implicated
in the acquisition of memories and in spatial navigation. We employ several in vitro
preparations and combine a range of molecular biology tools, electrophysiology and
pharmacology with the general aim of assessing the role of voltage- and Ca2+-activated ion
channels in the regulation of the firing properties of individual neurons and in the context of
the wider hippocampal circuitry. We are also interested in dissecting cellular mechanisms of
neuromodulation by transmitters such as acetylcholine, glutamate, GABA, monoamines and
neuropeptides, all of which mediate the fine-tuning of neuronal excitability through diverse
cellular pathways leading to changes in ion channel function. In this poster we present a
sample of the projects currently underway in our laboratory.
L19. CHRISTOS PROUKAKIS - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Presentation of the Department of Clinical Neuroscience, Royal Free Campus
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AUTHORS
Proukakis C
ABSTRACT
The UCL Institute of Neurology Department of Clinical Neuroscience is based at the Royal
Free Campus in Hampstead and headed by Professor Anthony Schapira. The main focus is
the investigation of the aetiology and pathogenesis of neurodegenerative disorders. The
department has already established an international reputation in the study of the clinical
evolution, genetics and cell biology of Parkinson’s disease in particular, with additional
ongoing work looking at experimental therapeutics in relevant models. Another area of
strength is the mitochondrial respiratory chain and disorders of mitochondrial function. There
are also research programmes on other extrapyramidal disorders, motor neuron disease,
peripheral neuropathy, hereditary spastic paraplegia, and Huntington’s disease. We have
strong links with the clinical neurology department, in which several of us also work. In
addition to Professor Schapira, there are six other Principal Investigators in the department;
clinical academics Professor Huw Morris, Dr Anette Schrag, Dr Richard Orrell, Dr Christos
Proukakis, and non-clinical academics Dr J Mark Cooper and Dr Jan-Willem Taanman.
L20. ANTONELLA RICCIO - MRC LABORATORY FOR MOLECULAR CELL BIOLOGY
Cristina Policarpi
POSTER TITLE
Novel mechanisms of gene expression in developing neurons
AUTHORS
Riccio lab
ABSTRACT
The goal of the Riccio lab is to understand how gene expression is regulated in neurons at
transcriptional and translational levels. The lab employs a wide array of sophisticated cell
and molecular biology techniques to manipulate gene expression in vivo and in vitro. There
are four main lines of research in the lab:
1) Nitric oxide-dependent regulation of gene expression in developing neurons. We
discovered that epigenetic factors become nitrosylated in response to physiological
stimulation and we are now performing a proteomic analysis to identify nuclear proteins
nitrosylated in cortical neurons.
2) Identification of the epigenetic mechanisms that regulate cortical development in vivo. A
genome wide analysis of genes regulated by HDAC2 has revealed that chromatin
remodelling factors represent novel targets of HDAC2 that are necessary for the proper
development of the cortex.
3) Understanding how nuclear architecture and chromatin structure contribute to gene
expression in response to synaptic activation. We identified a novel class of regulatory
elements that coordinate the expression of activity-dependent genes in cortical neurons.
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4) Transport and translation of mRNAs in axons of sympathetic neurons. We discovered
novel elements located within the 3’UTRs that are necessary for axonal transport and
translation of transcripts in response to neurotrophin stimulation.
L21. JASON RIHEL – UCL DEPARTMENT OF CELL AND DEVELOPMENTAL BIOLOGY
POSTER TITLE
Rihel Lab: Studying the genes and neurons that regulate sleep in zebrafish
AUTHORS
Rihel J
ABSTRACT
Sleep has fascinated poets, playwrights, philosophers, and scientists since antiquity. More
recently, increased public and clinical attention has focused on the negative health
consequences of the lack of adequate sleep. Despite this scrutiny, the mysteries of sleep’s
function and regulation endure. Why is sleep essential for animals as diverse as flies and
humans? What are the regulatory genes and neuronal circuits that control the timing,
amount, and duration of sleep? How can these control mechanisms go wrong in disease?
The Rihel lab uses zebrafish as a model system to investigate sleep. Zebrafish develop
rapidly, exhibiting a complex behavioral repertoire, including circadian rhythms, feeding and
sleep, by the fifth day of development. They are also optically transparent, facilitating the
direct study of neural circuits. Furthermore, zebrafish possess much of the conserved brain
circuitry thought to regulate sleep in humans. Thus, the zebrafish model is uniquely suited
for sleep studies, as it combines the genetic tractability of invertebrate models with the
sleep-relevant neural anatomy and physiology of mammals.
Current projects in the Rihel lab include the analysis of novel sleep and neurodevelopmental
mutants, small molecule screens for sleep-regulatory drugs, and in vivo calcium imaging of
sleep/wake circuits.
L22. CHRISTIANA RUHRBERG - UCL INSTITUTE OF OPHTHALMOLOGY
Francesca Mackenzie
POSTER TITLE
Class 3 semaphorins and neuropilins selectively organise boundary caps at axon entry/exit
points at the embryonic CNS-PNS interface
AUTHORS
Mackenzie F, Schwarz Q, Maden C, Davidson K, Charoy C, Ruhrberg C
ABSTRACT
Boundary caps (BC) are neural-crest-derived cell clusters on the surface of the brainstem
and spinal cord that mark the dorsal root entry zone (DREZ) of sensory nerves and motor
nerve exit points (MEPs) during embryogenesis. BCs are thought to guard the interface
between the peripheral and central nervous systems (PNS/CNS), allowing axons to cross
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whilst constraining cell bodies of neurons and other cell types, and have been suggested as
a possible regenerative therapy. Few genetic pathways have been identified that control BC
organisation or function. We demonstrate that SEMA3A and its receptor NRP1 is selectively
required for BC clustering and organisation at the DREZ, whilst SEMA3F and NRP2 are
specifically required for this process at MEPs. These defects are mirrored by specific defects
in axon patterning. Loss of both SEMA3A/3F or NRP1/2 leads to large ectopic boundary
cap-like structures, which associate with ectopic axons. In addition, culturing neural crest
cells with DRG induces expression of a boundary cap marker, suggesting that
neuronal/axonal presence may induce the differentiation of presumptive BC. Our results
suggest that SEMA3A and SEMA3F cooperate through NRP1 and NRP2 to restrict BC cells
to axon exit and entry points to ensure appropriate BC function.
L23. PATRICIA C SALINAS – UCL DEPARTMENT OF CELL AND DEVELOPMENTAL
BIOLOGY
POSTER TITLE
Understanding the mechanisms that trigger synapse degeneration and synapse recovery:
implications in neurodegeneration
AUTHORS
Salinas PC
ABSTRACT
Synapse loss is an early feature of neurodegenerative diseases such as Alzheimer's (AD),
and is correlated with cognitive decline. However, the molecular mechanisms that trigger
synapse disassembly remain poorly understood. Mounting evidence supports the
contribution of deficient Wnt signalling in AD. Our recent studies showed that Aß increases
the expression of a specific secreted Wnt antagonist Dickkopf-1 (Dkk1) in the hippocampus.
Importantly, we showed that blockade of Dkk1 with specific anti-Dkk1 antibodies protect
synapses against Aß toxicity. These results demonstrate that Dkk1 is downstream of Aß and
that endogenous Wnts are required for synapse integrity.
To understand the role of Dkk1, we generated an inducible transgenic mouse line that
expresses Dkk1 (iDkk1) in the adult hippocampus. Inducible Dkk1 expression results in a
40% reduction of excitatory synapses and impaired LTP, enhanced LTD and defects in long
term memory. Our aim now is to determine the cellular and molecular mechanisms that
trigger synapse vulnerability.
To examine whether synaptic function could be restored after synapse degeneration, we
used iDkk1 where Dkk1 expression was turned off for two weeks. This results in full
restoration of synapse number, full recovery of long-term plasticity and hippocampusmediated memory. These results highlight the robust regenerative capacity of mature
neurons. They also suggest that modulation of the Wnt pathway is a plausible therapy for
functional recovery in neurodegenerative diseases. We are taking a multidisciplinary
approach that combines proteomic and transcriptome analyses with cellular biology and
electrophysiology to unravel the mechanisms that contribute to synapse vulnerability and
synapse recovery.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
L24. KENNETH SMITH - UCL INSTITUTE OF NEUROLOGY
Sharmeen Haque
POSTER TITLE
Experimental Neuroinflammation Laboratory
AUTHORS
Smith KJ
ABSTRACT
Our primary research focus is central and peripheral neuroinflammatory demyelinating and
degenerating disease, such as multiple sclerosis (MS) which can cause blindness, paralysis
and numbness. Our laboratory focuses on innate immune mechanisms in
neuroinflammation, and their consequences. We have a particular interest in energy
metabolism, and believe that inflamed neural tissue suffers an energy deficit. We
consequently study mitochondrial biology, tissue oxygenation, and the vascular supply, as
well as the more conventional electrophysiological and pathological properties of the tissue,
giving us a relatively complete ‘picture’ of the influences within an inflammatory lesion and
their consequences. Techniques employed include confocal, spectroscopic and magnetic
resonance imaging in vivo, electrophysiology and light and electron microscopy. We believe
that an energy deficit contributes directly to four of the cardinal features of MS, namely loss
of function, demyelination, degeneration and fatigue. It follows that a therapy that corrects
the energy imbalance may help all the cardinal features in MS, as well as peripheral disease.
Our findings are relevant to the different neurological disorders in which neuroinflammation
plays an important role, which includes the range of neurodegenerative disorders.
L25. SELINA WRAY - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Stem Cell Models of Dementia
AUTHORS
Wray S
ABSTRACT
Our ability to create in vitro models of neurological disease has been greatly enhanced by
technological advances that allow terminally differentiated cells such as fibroblasts to be
repogrammed into stem cells. These induced pluripotent stem cells (iPSC) can be
differentiated into neurons, and as they contain the patients precise genome this results in a
physiologically-relevant disease model that can be used to understand disease mechanisms.
We collaborate closely with clinical colleagues in the Dementia Research Centre to collect
fibroblasts from patients with genetic forms of Alzheimer’s Disease (AD) and Frontotemporal
Dementia (FTD). Several of these have been converted into stem cells and we routinely
differentiate these cells into cortical, glutamatergic pyramidal neurons that are heavily
affected by pathology in FTD. We are using these neurons to understand the molecular
mechanisms of dementia, and ongoing projects in the lab include:
1. A microfluidics based assay for tau propagation (TS)
2. Understanding the role of astrocytes in 4R tauopathy (NSS)
3. Mitochondrial dysfunction in FTD caused by mutations in VCP (CA)
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
4. Modelling haploinsufficiency of C9ORF72 using genome engineered stem cells (EP)
5. Can the neuronal secretome help us understand mechanisms of disease? (JT/HW)
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Developmental Neuroscience | Jeffery Hall
1. DELI A - UCL CANCER INSTITUTE
POSTER TITLE
The stem cell factor Promyelocytic Leukaemia (Pml) regulates cell fate and migration in
normal and neoplastic neural stem cells
AUTHORS
A D, Henderson J, Amodeo V, Bartesaghi S, Oberndorfer S, Ozbey P, Roshani R, ShakedRabi M, McEvoy A, Dinsdale D, Jenner R, Nicotera P, Jones C, Brandner S, Salomoni P
ABSTRACT
The control of cell fate in neural progenitor/stem cells (NPCs) is essential for central nervous
system (CNS) development. Its alterations can give rise to neurodevelopmental syndromes
as well as brain cancer. Previously, we discovered that the promyelocytic leukaemia protein
(Pml), a tumour suppressor inactivated in leukaemia, controls corticogenesis in part via
relocalisation of the retinoblastoma tumour suppressor to the nuclear subdomain called Pmlnuclear body (Pml-NB), with implications for regulation of brain size.
NPCs are found also within two specialised neurogenic niches of the adult brain, the
subventricular zone and the dentate gyrus. NPCs within the SVZ migrate through the rostral
migratory stream (RMS) to generate new neurons in the olfactory bulb (OB). Here, we
demonstrate that loss of Pml leads to decreased RMS migration and a smaller OB.
Mechanistically, PML regulates migration via activation of a transcriptional programme
involving epithelial-to-mesenchymal transition and axon guidance genes. Notably, this axis is
in part retained in primary brain tumour cells, suggesting that Pml may bear oncogenic
functions in brain cancer.
Overall, these findings have important implications for our understanding of adult
neurogenesis and may provide novel insights into the process of transformation in the CNS.
2. CHARLES ARBER - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Investigating molecular mechanisms of VCP/p97 neurodegeneration through patient iPSderived neurons
AUTHORS
Arber C, Ludtmann M, Preza E, Soutar M, Hardy J, Houlden H, Plun-Favreau H, Abramov A,
Wray S
ABSTRACT
Mutations in Valosin-containing protein (VCP, also known as p97) lead to inclusion body
myopathy, Paget’s disease of the bone and frontotemporal dementia (IBMPFTD) as well as
amyotrophic lateral sclerosis (ALS). VCP is a widely expressed AAA+ ATPase that is
involved in the ubiquitin proteasome pathway for normal protein turnover and degradation.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
VCP has many cellular functions that include mitophagy, DNA damage repair, cell cycle
progression and ER-associated degradation.
In this study we have reprogrammed fibroblasts from two patients carrying VCP mutations
into induced pluripotent stem cells (iPSCs) and subsequently differentiated patient and
control iPSCs into cortical neurons. Investigations into mitochondrial physiology, stress
granule clearance and DNA damage repair are currently underway to investigate disease
phenotypes in the mutant cells. Additionally, RNA-seq and proteomics will enable a global
profile of disease phenotypes that lead to neurodegeneration.
A better understanding of the cellular mechanisms of VCP-driven neurodegeneration will not
only enhance our understanding of disease progression, but also help define therapeutic
targets in the future. Linking VCP mutations with other gene defects that lead to
frontotemporal dementia may help define a common pathway and a better understanding of
the disease as a whole.
3. CRISTINA BENITO SASTRE - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL
BIOLOGY
POSTER TITLE
STAT3 is required for the long-term maintenance of the repair Schwann cell phenotype in
injured nerves
AUTHORS
Benito C, Davis C, Mirsky R, Jessen KR
ABSTRACT
After nerve injury STAT3 is activated in the axons of PNS neurons at the injury site and
retrogradely transported to the cell body where it activates genes involved in axon
regeneration and neuronal survival. The role of this factor in Schwann cells (SCs) of injured
nerves has not been extensively investigated.
In the distal stump of injured nerves, the loss of axonal contact triggers the reprogramming
of SCs to form repair (Bungner) SCs. In larger animals, the Bungner cells in more distal
parts of regenerating nerves are deprived of axonal contact for a long time, as axonal
regeneration progresses more proximally. These long-term denervated SCs gradually lose
their ability to support axon growth and eventually die.
Our findings reveal that nerve injury results in STAT3 phosphorylation in the SCs in the distal
nerve stump. The survival of SCs in long-term denervated distal stumps is markedly reduced
in mice with conditional deletion of STAT3 in SCs. STAT3 is also required for the long-term
maintenance of structurally normal regeneration tracks (Bands of Bungner).
We suggest that STAT3 is required for the prolonged maintenance of the repair phenotype
and for the long-term survival of the Bungner repair cells.
4. KAREN EASTLAKE - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
Müller glia-derived cytokines are predominantly increased in the gliotic human retina.
AUTHORS
Eastlake K, Banerjee PJ, Angbohang A, Becker, S, Charteris DG, Limb GA
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
ABSTRACT
Although it is well documented that cytokines and growth factors play a key role in retinal
gliosis, the effects of cytokine activation by resident human Müller stem cells(hMSC) has not
been addressed.Protein lysates of hMSC, normal and gliotic retina(obtained with consent
from MEH) were examined for cytokine expression using a dot-blot and multiplex
immunoassays. Qualitative cytokine arrays showed that 24 cytokines exhibited >100%
increase in the gliotic retina compared with the normal retina. Additionally, out of 102 factors
detected in the gliotic retina, 76 were also detected in hMSCs. Quantitative cytokine arrays
revealed a significant increase in the levels of 19 cytokines in the gliotic retina compared to
the normal retina. Interestingly, many of the cytokines produced by hMSC were found to be
highly upregulated in the gliotic retina, including eotaxin, GCSF, MCP-1, PDGF-bb,
RANTES, TNFα, VEGF and TGFβ2 (P<0.05 to P<0.001). The similarity in the cytokine
expression pattern between hMSCs and gliotic retina suggests that hMSCs may be the
principal source of cytokines present in the gliotic retina. It is hoped that results of this study
will lead to investigations of the effects of selective cytokines on the inhibition of the
regenerative ability of hMSCs in the human retina.
5. SHALINE FAZAL - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL BIOLOGY
POSTER TITLE
The role of c-Jun in regenerating nerves
AUTHORS
Fazal S, Benito C, Gomez-Sanchez J, Mirsky R, Jessen K
ABSTRACT
The formation of effective repair (Büngner) Schwann cells, that are essential for nerve
regeneration, depends on the upregulation of Schwann cell c-Jun within distal nerve stumps.
Here we show that c-Jun is also activated in Schwann cell nuclei proximal to the injury, as
early as 1hr after nerve transection. c-Jun expression is highest 0-2mm from the injury and
lasts at least for 48hrs, with its function yet to be established.
The regeneration support provided by the distal nerve stump decreases with time after
injury. Initially c-Jun is rapidly activated in distal stump Schwann cells, and continues to rise
from 3-7days after injury, but, significantly, decline at 6 weeks.
Additional correlation between c-Jun and regeneration was found in mice that show
accelerated regeneration because of conditional deletion of the Notch signaling protein RBPj
in Schwann cells. We show that c-Jun expression in the nuclei of Schwann cells of
regenerating nerves is significantly elevated in RBPj mutants compared to WT controls.
Together, these experiments open new questions about the role of c-Jun in Schwann cells
proximal to nerve injury, suggest that c-Jun is involved in maintaining the repair Schwann
cell phenotype and indicate that enhanced activation of c-Jun could promote nerve repair.
6. ROBERT GABRIEL - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
Immunolocalisation of Tubulin Polymerisation Promoter Protein TPPP/p25 in the retina
AUTHORS
Tripon RG, Nasir T, Csincsik L, Olah J, Ovadi J, Lengyel I
ABSTRACT
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Purpose: Tubulin Polymerization Promoting Protein (TPPP/p25) is crucial in
oligodendrocytes for differentiation and development of projections through interaction with
the microtubule system. In this work we screen the expression of TPPP/p25 in the retina of
mice and human eyes by immunofluorescent confocal microscopy.
Methods: Paraffin embedded sections from human and mice eyes were obtained from UCL
Institute of Ophthalmology with Institutional Ethics Committee approval.
Immunohistochemistry was performed using TPPP/p25, calbindin and acetylated-tubulin
specific antibodies on paraformaldehyde fixed samples. Labelling was visualized by confocal
microscopy using fluorescently labelled secondary antibodies.
Results: TPPP/p25 was detected in both human and mouse retina in selected cell bodies in
the inner nuclear layer and ganglion cell layer. Co-labelling with calbindin highlighted that
TPPP/p25 is enriched in amacrine cells and their projections to the inner plexiform layer ‘s
S1, S3 and S5 sub-laminas and outer plexiform layer (OPL). Immunoreactivity in flat-mount
retina showed that less than 10% of amacrine cells were labelled with TPPP/p25 antibodies.
Double-labelling with TPPP/p25 and acetylated-tubulin specific antibodies showed colocalisation.
Conclusions: TPPP/p25 is associated with a subclass of amacrine cells and their projections
to the OPL and S1, S3 and S5 sub-laminas of the IPL, and could be involved in the
development and stability of the dendritic arborisation.
7. RENATO GOMES DA SILVA MARTINHO - UCL DEPARTMENT OF CELL AND
DEVELOPMENTAL BIOLOGY
POSTER TITLE
The Asymmetric Habenula of Zebrafish: from transcriptome to behaviour
AUTHORS
Martinho R, Dreosti E, Wilson SW
ABSTRACT
Many vertebrates’ organs and structures are morphological and functionally asymmetric. A
well known example is the habenula, a conserved paired-nuclei structure in the vertebrate
brain. In Zebrafish, the dorsal part of the Habenula has evident anatomical asymmetries and
its left and right nuclei are differently activated by light and odour stimuli. Working as a relay
station between the forebrain and the midbrain, the Habenula seems to have a role in
several processes such as in learning behaviour. However, the main function of its neuronal
subpopulations and the importance of their asymmetry is still unknown. Therefore, we intend
to profile habenulae neurons by single-cell transcriptomics and cluster them into
subpopulations. Then, once we identify key markers for each subpopulation, we aim to
characterise them by modulating their activity and determine the corresponding function
using learning behaviour assays as an output. With this work we expect to bring together the
molecular singularities of the habenula with its functional output and to add a new tool for the
study of brain asymmetry using the habenula of zebrafish.
8. CITLALI HELENES GONZALEZ - UCL INSTITUTE OF CHILD HEALTH
POSTER TITLE
New three-dimensional models for the study of normal and abnormal human neural
development
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
AUTHORS
Helenes González C, Ferretti P, Jayasinghe SN
ABSTRACT
There is much need for developing 3D (3-dimensional) systems that can better mimic the
behavior of human tissues and provide reliable models for studying human central nervous
system (CNS) development and function.
Our aim is to establish a novel 3D model using different matrices to build a scaffold to
support human neural stem/progenitor cells (hNSCs) derived from embryonic CNS and their
differentiated progeny to mimic the in vivo environment of the human CNS. We are using the
Bio-electro spraying (BES) technique in order to build this 3D model. This approach consists
of a needle-based delivery system driven by an electric field that can be used to generate
cell-laden fibres and scaffolds into specific architectures at the micro and nano scale.
A crucial issue for the use of BES is maintenance of cell viability and normal behaviour after
bio-electrospraying. Embryonic hNSCs were sprayed and their survival and capacity to
differentiate into neurons, oligodendrocytes and astrocytes was assessed.
Overall hNSCs did not show significant alteration after spraying, hence BES can be used to
model a neural tissue. Selection of suitable matrices for hNSCs spraying to build a 3D model
is in progress.
9. SHABANA KHAN - THE FRANCIS CRICK INSTITUTE
POSTER TITLE
Characterising the role of NeuroD6 in a novel subset of midbrain dopaminergic neurons
AUTHORS
Khan S, Stott S, Truckenbrodt A, Chabrat A, Lévesque M, Ang SL
ABSTRACT
Midbrain dopaminergic (mDA) neurons represent a large heterogeneous pool of neurons
that differ in their cellular location, projection pattern, connectivity to target areas, synaptic
inputs and outputs and subsequently function. It is now becoming clear that the substantia
nigra (SN) and ventral tegmental area (VTA) subpopulations comprise of molecularly and
functionally distinct mDA neuronal subsets and how these neurons comprise such diversity
is not well understood. Here, we report the identification and characterisation of a novel
subset of mDA neurons of the VTA that express a basic helix-loop-helix (bHLH) transcription
factor (TF) called neurogenic differentiation factor-6 (NeuroD6). By combining a knock-in
strategy and a loss-of-function approach, we have characterised this mDA neuronal subset
at late embryonic, early-postnatal and adult stages. These NeuroD6-expressing mDA
neurons are localised in the medial VTA and specifically populate the interfasicular nucleus
(IFN), dorsal and ventral paranigral nucleus (PN) and the lateral VTA of the midbrain. We
have also shown that they are a subset of the calbindin+/ Otx2+ subpopulation of the VTA.
In the absence of NeuroD6, a 32% reduction in cell number occurs within the medial VTA of
mutants and this reduction is observed within the IFN, dorsal PN and lateral VTA suggesting
that NeuroD6 is required for their survival. Furthermore, retrograde experiments targetting
the lateral septum (LS) using fluorogold neuronal tracer in controls, have demonstrated that
the NeuroD6-expressing mDA subset of neurons specifically project to the LS. In the
absence of NeuroD6, mDA axonal projections are lost within the intermediate LS. In
summary, we report the identification of a novel subset of mDA neurons characterised by
their expression of NeuroD6 and their specific axon projection patterns. Together, these
insights shed light on the heterogeneity of mDA neurons.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
10. TIM KROECHER - MRC LABORATORY FOR MOLECULAR CELL BIOLOGY
POSTER TITLE
Identifying novel regulators of axon growth
AUTHORS
Kroecher T, Mencarelli C, Pichaud F
ABSTRACT
Neuronal function depends on cellular polarization, dividing neurons into somatodendritic
and axonal domains. The signaling cascades underlying neuronal polarity and initial axon
growth have been extensively studied. However cellular and molecular mechanisms that
regulate axonal growth remain relatively elusive. To identify novel genes required for axon
growth in vivo, we have performed an RNAi screen using the Drosophila larval
photoreceptors, the Bolwig’s Organ (BO). The BO projects a nerve that targets the nascent
embryonic brain. During larval growth, this nerve lengthens in proportion with the overall size
of the animal. Our screen identified 80 candidate genes important for BO morphogenesis,
including axon growth. These genes regulate processes such as membrane trafficking,
cytoskeleton remodeling, cellular signaling and metabolism. Amongst our candidate genes,
we have identified the Ins(1,4,5)P3-5-phosphatase (Inpp5a) as a regulator of BO nerve
elongation. Inpp5a regulates IP3-dependent Ca2+ release from the endoplasmic reticulum.
We will present work in progress that is aimed at characterizing this novel role of Inpp5a in
Drosophila neurons in vivo but also in rat neurons in vitro.
11. CHIARA MENCARELLI - MRC LABORATORY FOR MOLECULAR CELL BIOLOGY
POSTER TITLE
Identifying novel genes and mechanisms regulating axon growth
AUTHORS
Mencarelli C, Kroecher T, Pichaud F
ABSTRACT
Neurons are highly polarized cells whose function relies on the differentiation of the axon
and dendrites. Although some of the signaling pathways important for axon specification
have been identified, little is known about the cellular and molecular processes involved in
building an axon.
To identify novel genes required for axon growth in vivo, we have performed an F1 RNAi
screen using the Drosophila larval visual system, the Bolwig’s Organ (BO), as a model
system. The BO projects a nerve that targets the nascent embryonic brain. As the larval
grows, this nerve must lengthen in proportion with the overall size of the animal. Our screen
identified 80 candidate genes important for BO morphogenesis, including axon growth.
These genes regulate process such as membrane trafficking, cytoskeleton remodeling and
cellular signaling.
In particular, we have identified the Ran-GTPase as required for BO nerve morphogenesis.
While Ran is a main regulator of nuclear export and microtubule organization during spindle
assembly, our preliminary data indicate that Ran also regulates axon specification in both
flies and vertebrate. We will present work in progress that is aimed at characterizing this new
function.
12. POSTER WITHDRAWN
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
13. SUBATHRA POOPALASUNDARAM - UCL DIVISION OF MEDICINE
POSTER TITLE
Specification and migration of gonadotrophin releasing hormone (GnRH) neurons
AUTHORS
Poopalasundaram S, Graham A, Bouloux P
ABSTRACT
The hypothalamic gonadotrophin releasing hormone (GnRH) neurons are a small group of
cells that regulate the reproductive axis. These neurons are specified within the olfactory
placode, delaminate and then migrate to enter the forebrain before populating the
hypothalamus.
Microarray technology was employed to analyse the transcriptome of the chick olfactory
placode at a number of key developmental time points important for GnRH ontogeny. One of
the genes upregulated at the time when GnRH neurons are migrating from the olfactory
placode to the forebrain is serotonin (5-HT) receptor 1A, HTR1A. We have mapped the
expression of HTR1A in chick embryos and used pharmacological agents to study the
functional requirement for HTR1A.
We find that HTR1A is expressed in the olfactory placodal region that gives rise to GnRH
neurons. When the receptor was inactivated using a selective antagonist to HTR1A, it
delayed the migration of GnRH neurons into the forebrain, with the GnRH neurons
accumulating just outside the forebrain. These findings implicate HTR1A as being important
for GnRH neuronal migration.
Understanding the functional significance of the novel genes isolated will add to the
repertoire of genes involved in GnRH neuron biology and help to identify new candidate
molecules to screen patients who do not show any mutations in any of the thus identified
HH/KS genes.
14. AMY VINCENT - UCL INSTITUTE FOR WOMEN’S HEALTH
POSTER TITLE
The duration of hypothermia affects neuroprotection in a mouse model of neonatal hypoxic
ischaemic injury
AUTHORS
Vincent A, Rocha-Ferreira E, Peebles D, Hristova M
ABSTRACT
Neonatal hypoxia-ischaemia (HI) around the time of birth is major source of mortality and
morbidity in children. Current treatment for hypoxic-ischaemic neonates is therapeutic
hypothermia (TH), but it is only partially effective. Therefore, research into adjunct therapies
to combine with TH is required. Murine models of neonatal HI exist, but a neonatal mouse
model of TH post-HI is not established yet and is essential for testing adjunct therapies.
The aim of our study was to compare exposure of neonatal P7 mice to different durations of
TH post-HI and determine the neuroprotective effects.
While 1h TH did not change the levels of microglial activation, TUNEL+ cell death or tissue
loss, 2h TH significantly reduced all histological damage markers compared to normothermic
littermate controls. Exposure to 1.5h TH weakly reduced microglial activation and TUNEL+
cell death, but significantly decreased tissue loss.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Therefore in this mouse model exposure to 2h TH is highly neuro-protective, yet its clinical
relevance is questionable in respect to the fact that >50% of HI infants treated with
hypothermia still develop neuro-disabilities. Thus as 1.5h hypothermia provides some,
although limited protection following neonatal HI it appears to be the most suitable duration
for combined treatment and adjunct therapies testing.
15. LAURA WAGSTAFF - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL
BIOLOGY
POSTER TITLE
The role of c-Jun in Schwann cells during long-term injury of the peripheral nervous system
AUTHORS
Wagstaff LJ, Gomez-Sanchez JA, Mirsky R, Jessen KR
ABSTRACT
Following peripheral nerve injury, Schwann cells down-regulate their myelinating phenotype
and activate a repair programme that facilitates axon survival and regeneration. When c-Jun
is specifically knocked-out in Schwann cells, this repair phenotype is not observed. Trophic
factors are not up-regulated, axon regeneration is poor and neuronal and Schwann cell
death is observed. This suggests that c-Jun controls the activation of this repair programme.
Despite this repair programme, long-term nerve regeneration in humans is poor. It was
hypothesized that the repair phenotype of the Schwann cells is not maintained during longterm injury. As the repair programme is controlled by c-Jun, c-Jun expression was examined
following long-term injury. C57/B6 mice underwent a sciatic nerve cut followed by long or
short-term denervation. Protein and immunohistochemical analysis was performed on the
distal nerve stumps and c-Jun was shown to decrease over time following long term
denervation. Dual staining of c-Jun with Schwann cell marker Sox10 demonstrated that this
decrease was occurring in the Schwann cells but also showed that Schwann cell numbers
decreased. It is now hypothesized that maintaining c-Jun expression during long-term injury
could maintain the repair phenotype of Schwann cells leading to decreased apoptosis,
maintenance of trophic support and increased axon regeneration.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Neural Excitability, Synapses and Glia: Cellular Mechanisms | Elvin Hall
16. SANA AL AWABDH - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Neuronal activity mediated regulation of glutamate transporter GLT1 surface diffusion in
astrocytes
AUTHORS
Al Awabdh S, Sheehan D, Muir J, Norkett R, Vaccaro V, Kittler JT
ABSTRACT
Controlling the extracellular concentration of glutamate in the brain is crucial for normal
signalling and to prevent neurotoxicity. The astrocytic GLT1 is the major glutamate
transporter for clearing synaptic glutamate. However, little is known regarding the
mechanisms that regulate surface dynamics of GLT1. Modulating GLT1 surface diffusion
could play a key role in regulating local glutamate uptake and synaptic activity. Here, we
have used live cell imaging to study the mechanisms regulating GLT1 surface diffusion in
astrocytes. We show a rapid and reversible dispersal of surface GLT1 clusters upon
glutamate treatment, correlating with an increase in GLT1 surface mobility. Blocking the
transporter activity prevented this glutamate-dependent dispersal. By using single particle
tracking, we showed that GLT1 is highly dynamic and, remarkably, more mobile in the
presence of neurons. Interestingly, the two main GLT1 C-terminal isoforms expressed in the
adult brain, Glt1a and Glt1b, are both found to be stabilised in apposition to synapses.
Furthermore, alterations in neuronal activity modulate the dynamics of GLT1a and GLT1b.
Altogether, these data reveal that the astrocytic GLT1 surface mobility is modulated during
neuronal activity, which may play a key role in shaping glutamate clearance and
glutamatergic synaptic transmission.
17. ANGSHUMONIK ANGBOHANG - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
Downregulation of the canonical Wnt signalling pathway by TGF-β1 inhibits photoreceptor
differentiation of adult human Müller stem cells
AUTHORS
Angbohang A, Charalambous T, Wu N, Eastlake K, Becker S, Lei Y, Sun X, Limb GA
ABSTRACT
Müller glia regenerate adult zebrafish retina after injury. Müller glia with stem cell
characteristics (hMSC) can be isolated from the adult human retina to differentiate into
photoreceptors in vitro. Activation of Wnt signalling promotes proliferation and differentiation
of neural progenitors, whilst transforming growth factor-β (TGF-β) has been shown to
regulate zebrafish photoreceptor regeneration. We investigated whether TGF-β may control
Wnt signalling pathway and whether it may influence the ability of hMSC to differentiate into
photoreceptors in vitro. hMSC cultured with FTRI increased gene and protein expression of
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
WNT2B and β-catenin. Whilst TGF-β1 decreased gene and protein expression of WNT2B
and β-catenin, it also inhibited differentiation of hMSC into photoreceptors as judged by
decreased expression of NR2E3 and recoverin. The TGF-β type I receptor inhibitor
SB431542 and the Smad3 inhibitor SIS3 blocked TGF-β inhibition of WNT2B. Addition of
the β-catenin inhibitor XAV-939 to hMSC undergoing differentiation prevented upregulation
in gene and protein expression of NR2E3 and recoverin. The results suggest that downregulation of the canonical Wnt signalling pathway by TGF-β1 inhibits hMSC photoreceptor
differentiation. It would be therefore important to investigate how these pathways can be
modulated in order to induce endogenous regeneration of the adult human retina.
18. POSTER WITHDRAWN
19. JACKIE CASEY - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Glutamate increases the lateral mobility of GABAB receptors
AUTHORS
Casey JM, Hannan S, Smart TG
ABSTRACT
γ-aminobutyric acid type-B receptors (GABABRs) are G-protein coupled receptors that are
activated by GABA, the main inhibitory neurotransmitter in the brain. The localization of
these receptors near excitatory postsynaptic compartments makes them an important
candidate for modulating the effects of excitatory neurotransmission by GABA. Over the last
decade, lateral diffusion of neurotransmitter receptors has emerged as a key pathway for the
delivery of receptors to postsynaptic specialisations. Here, we track the real-time lateral
mobility of single GABABRs on surface membranes of murine hippocampal cultured
neurons. Extrasynaptic GABABRs were found to move significantly faster and diffuse further
than those found at synaptic or perisynaptic regions around PSD95-containing excitatory
synapses. The application of glutamate significantly increased the speed and membrane
area traversed by GABAB receptors in both membrane domains. This may reflect an
increase in the trafficking of GABAB receptors in the presence of glutamate. Altering the
number and equilibrium of receptors on the membrane surface is likely to affect the function
and efficiency of synapses and could reflect a mechanism to protect against excitotoxicity.
20. LORENZA CIANI - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL BIOLOGY
POSTER TITLE
Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1
AUTHORS
Ciani L, Marzo A, Boyle K, Stamatakou E, Lopes D, Anane D, Gibb G, Salinas PC
ABSTRACT
The functional assembly of the synaptic release machinery is well understood, but how
signalling molecules modulate this process remains unknown. Recent studies suggest that
Wnts play a role in presynaptic function. To examine the mechanisms involved, we
investigated the interaction of release machinery proteins with Dishevelled-1 (Dvl1), a
scaffold protein that determines the cellular locale of Wnt action. We found that Dvl1 directly
interacts with Synaptotagmin 1 (Syt-1) and indirectly with the SNARE proteins SNAP25 and
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Syntaxin (Stx-1). Importantly, the interaction of Dvl1 with Syt-1, which is regulated by Wnts,
modulates neurotransmitter release. Moreover, presynaptic terminals from Wnt signalling
deficient mice exhibit reduced release probability and are unable to sustain high frequency
release. Consistently, the readily releasable pool size and formation of SNARE complexes
are reduced. Our studies demonstrate that Wnt signalling tunes neurotransmitter release
and identify Syt-1 as a target for modulation by secreted signalling proteins.
21. SHEHRAZADE DAHIMENE - UCL DEPARTMENT OF NEUROSCIENCE,
PHYSIOLOGY & PHARMACOLOGY
POSTER TITLE
CaV2.1 N-terminal residues reduce the suppressive effect of the truncated Episodic Ataxia-2
mutant on the wild-type Cav2.1
AUTHORS
Dahimene S, Page KM, Nieto-Rostro M, Pratt WS, D'Arco M, Dolphin AC
ABSTRACT
Episodic ataxia-2 is an autosomal dominant disorder caused by mutations of the CACNA1A
gene that encodes for the pore forming calcium channel subunit CaV2.1. This channel is
preferentially expressed in presynaptic terminals where it plays a central role in
neurotransmitter release. The majority of episodic ataxia-2 mutations reported so far are
nonsense or deletion/insertion mutations predicted to form truncated proteins. Heterologous
expression of wild-type CaV2.1 channel together with the truncated constructs that mimic
episodic ataxia-2 mutants significantly suppressed wild-type channel function, indicating that
the truncated protein produces a dominant- negative effect (Jouvenceau et al.,2001; Page et
al.,2004). A similar finding has been shown for CaV2.2 (Raghib et al.,2001). In addition, the
suppression effect required interaction between the full-length and the mutant construct. We
aimed to develop a cellular assay in order to disrupt the destructive interaction between wildtype and episodic ataxia-2 mutant CaV2.1 channels and therefore restore partially or totally
the trafficking and function of the wild-type CaV2.1. Using a cell imaging assay, we have
confirmed that the truncated CaV2.2 protein (Dom I-II) prevents full-length CaV2.2 from
reaching the plasma membrane. We have also confirmed that the N-terminus residues for
both Cav2.1 and Cav2.2 channels which are highly conserved among CaV2 family are
involved in this process. Additionally, it was possible to prevent the suppressive effect of the
truncated protein by coexpressing constructs that mimic the key N-terminal residues. By
doing so we were able to restore partially the function of the full-length channel. We
postulate that the N-terminus is essential for the truncated proteins to interact with the fulllength channel and as a result prevent the correct folding of the wild-type channel.
Therefore, coexpressing the key N-terminal residues, would prevent the deleterious
interaction.
22. LAURA FEDELE - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Dysfunctional glutamatergic NMDA receptors in disease
AUTHORS
Fedele L, Smart TG, Harvey RJ
ABSTRACT
28
2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that together
with AMPA and kainate receptors mediate the majority of fast excitatory neurotransmission
in the CNS, whose dysfunction is likely to affect brain physiology and behaviour.
Recently, de novo mutations in the GluN2B subunit gene of NMDARs (GRIN2B) were
detected in patients with numerous neurological disorders (e.g. autism spectrum disorders,
epilepsies and intellectual disabilities).
Here we assess how these mutations affect the physiological and pharmacological
properties of NMDARs in disease states.
NMDAR point-mutations associated with disease were assessed for pathogenicity using
bioinformatics tools. We constructed a 3D model of the human NMDA GluN2B subunit,
based upon recent crystal structures to identify the location of the pathogenic residues and
their potential impact on neighbouring amino acids.
The functional effects of the mutations were assessed by using whole-cell patch clamp
electrophysiology.
Our results suggest that we can associate specific NMDAR mutations with distinct
phenotypes, including changes in: glutamate potency; Mg2+ voltage-dependent block and
channel current kinetics.
Some mutations did not cause significant changes in NMDAR function, suggesting other
mechanisms in the pathophysiology of those patients.
Overall, our analyses should indicate which pharmacotherapeutic interventions are likely to
be successful in treating patients carrying NMDAR mutations.
23. MARC FORD - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Tuning of myelinated axon properties to preserve temporal information
AUTHORS
Ford MC, Alexandrova O, Cossell L, Grothe B, Attwell D
ABSTRACT
Action potential timing is fundamental to information processing, but its determinants are
incompletely understood. Here we report unexpected structural specializations of myelinated
axons that help to preserve temporal information for sound localization. Using fibre tracing
and immunolabelling of nodal and juxtaparanodal marker proteins, we found that myelination
parameters of globular bushy cell axons of the mammalian auditory brainstem deviate from
the canonically assumed structure and specifically tune axon properties depending on the
sound frequency they are tuned to. Low-frequency axons had a larger diameter than highfrequency axons, but, surprisingly, shorter internodes. This deviation from the generally
assumed axonal structure helps to tune the conduction speed and timing of action potentials
within the circuit. Moreover, along the distal part of these axons, internode length decreases
and Ranvier node diameter increases progressively, which we show is essential to ensure
precisely-timed depolarization of the giant calyx of Held presynaptic terminal. Thus,
individual anatomical parameters of myelinated CNS axons can be tuned to optimize
information processing.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
24. LEA GOETZ - WOLFSON INSTITUTE OF BIOMEDICAL RESEARCH AT UCL
POSTER TITLE
Biophysical modelling of synaptic input patterns
AUTHORS
Goetz L, Roth A, Hausser M
ABSTRACT
Theoretical modeling and in vitro experiments have shown that the computations performed
by single neurons critically depend on the spatiotemporal input patterns to the neuron.
However, the synaptic input patterns received by neurons in vivo remain unknown. We
implement different spatio-temporal patterns of synaptic input on a detailed biophysical
model of a mouse L2/3 pyramidal cell and reproduce dendritic non-linearities and firing
behaviour observed in vivo. We can thus describe how excitatory and inhibitory synaptic
input distributions define the computational power of individual dendrites and make
predictions for in vivo synaptic input distributions during behaviour.
25. TIMO GREINER - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
The kinetic properties of the human glycine receptor in response to different agonists
AUTHORS
Greiner T, Hurdiss EJ, Yu R, Lape R, Biggin PC, Sivilotti LG
ABSTRACT
Glycine receptors are ligand-gated chloride channels that mediate fast synaptic inhibition in
the spinal cord and brainstem. In this study, we characterised the response of glycine
receptors with the patch-clamp technique in the whole-cell configuration, to different agonists
other than glycine. We selected two agonists, β-alanine and D-alanine, for a more detailed
single channel analysis. By fitting kinetic schemes to the obtained data we were able to get
insight into the differences in binding and gating of the glycine receptor in response to the
different agonists. The data from both agonists tested could be fitted well with the flip
mechanism that used 3 agonist molecules and pre-open flip states. While binding and gating
rate constants of these agonists all remained relatively similar to that of glycine, the main
difference was the ability of the agonist to stabilise the pre-open flipped confirmation.
Additionally, the less effective agonist D-alanine proved to have a lower binding affinity than
glycine and β-alanine. This is in agreement with previous conclusions that the determinant of
the partiality of an agonist is its ability to stabilise the flipped confirmation of the receptor.
And, with the help of Molecular dynamics modelling, we received structural insight to our
findings.
26. SOPHIE LEACOCK - UCL SCHOOL OF PHARMACY
POSTER TITLE
A novel zebrafish mutant with defective escape behaviour caused by a mutation in a DEAHbox RNA helicase gene regulating glycine receptor expression
AUTHORS
Hirata H, Ogino K, Yamada K, Leacock S, Harvey RJ
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
ABSTRACT
We report the isolation and characterisation of a novel zebrafish mutant that exhibits an
abnormal dorsal bend in the beginning of tactile-evoked escape swimming. Similar
behavioural defects were observed in zebrafish embryos treated with strychnine, an
antagonist of glycine receptors (GlyRs), suggesting that the abnormal motor response in
mutants is attributable to a deficit in glycinergic synaptic transmission. Indeed, blocking
GlyT1, which terminates glycinergic transmission, ameliorated the abnormal touch response
in this mutant. Unexpectedly, positional cloning resulted in the identification of a missense
mutation (p.L489P) in dhx37, encoding the DEAH-box RNA helicase Dhx37. RNA helicases
regulate RNA metabolism, but their substrate specificity and in vivo function remain largely
unknown. In the dhx37 mutant, we found that rRNA levels were unchanged, whereas GlyR
α1, α3, and α4a subunit transcript levels were decreased and mis-spliced. We found that
Dhx37 can interact with GlyR α1, α3, and α4a subunit transcripts, but not the GlyR α2
subunit mRNA. Consistent with this finding, over-expression of GlyR α1, α3 or α4a subunits
in Dhx37-deficient embryos restored normal behaviour. Conversely, antisense-mediated
knockdown of multiple GlyR α subunits in wild-type embryos was required to re-capitulate
the Dhx37 phenotype. These results indicate that Dhx37 is specifically required for the
biogenesis of a subset of GlyR α subunit mRNAs, thereby regulating glycinergic synaptic
transmission and associated motor behaviors. To our knowledge, this is the first
identification of pathologically relevant substrates for a RNA helicase. Our study also
suggests that mutations in human DHX37 may cause a disease associated with defective
glycinergic transmission. In particular, startle disease/hyperekplexia affects newborn children
and is characterized by exaggerated startle reflexes in response to sudden, unexpected
auditory or tactile stimuli. Defects in GlyR α1 subunit, β subunit or GlyT2 genes are the
major known genetic causes of startle disease/hyperekplexia in humans. However, many
individuals do not harbour mutations in these genes. Sequencing of human DHX37 is now a
major priority in these cases and may reveal a new genetic cause of human startle disease.
27. POSTER WITHDRAWN
28. AMY MCTAGUE - UCL INSTITUTE OF CHILD HEALTH
POSTER TITLE
Loss-of-function mutations in SLC12A5 in autosomal recessive migrating partial seizures of
infancy (MPSI)
AUTHORS
McTague A, Stödberg T, Ruiz AJ, Hirata H, Zhen J, Long P, Farabella I, Meyer I, Kawahara
A, Vassallo G, Stivaros SM, Bjursell MK, Stranneheim HK, Tigerschiöld H, Persson B,
Bangash I, Das K, Hughes D, Lesko N, Lundeberg J, Scott RC, Poduri A, Scheffer IE,
Schorge S, Reith MEA, Topf M, Kullmann DM, Harvey RJ, Wedell A, Kurian MA
ABSTRACT
We report the identification of recessive loss-of-function SLC12A5 mutations in a severe
infantile-onset pharmacoresistant epilepsy syndrome, migrating partial seizures of infancy
(MPSI). Acquired KCC2 dysfunction has been implicated in human epilepsy, but no
monogenic KCC2-related epilepsy disorders have been described.
Using a combination of homozygosity mapping and whole exome sequencing in two families
with MPSI, recessive mutations were identified in four affected children. Protein homology
modelling studies predicted damaging effects on the structure-function of KCC2.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Immunoblotting and surface protein biotinylation demonstrated reduced total and cell surface
expression levels of mutant KCC2 and decreased protein glycosylation , indicating impaired
post-translational processing. Voltage clamp experiments in HEK-293 cells transiently
transfected with the glycine receptor α2 subunit and KCC2 showed that KCC2 mutants
exhibit a depolarised ECl relative to wild–type KCC2. Finally, TALEN-mediated genome
editing was undertaken to generate a KCC2a-KCC2b double knockout zebrafish model,
which showed abnormal jerky spasmodic movements during the escape response.
The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental
role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions.
Impaired chloride extrusion contributes to loss of KCC2 activity, thereby impairing normal
synaptic inhibition and promoting neuronal excitability in this early-onset epileptic
encephalopathy.
29. ANUSHA MISHRA - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
The role of astrocytes in neurovascular coupling at the capillary level
AUTHORS
Mishra A, Chen Y, Attwell D
ABSTRACT
Neuronal activity results in a spatially and temporally localized increase in blood flow to meet
the increased demand for oxygen and glucose. Neurovascular coupling was classically
thought to occur at the arteriole level, where it is mediated, at least in part, by the release of
vasoactive arachidonic acid (AA) metabolites from astrocytes. We now know that cerebral
blood flow can also be controlled at the capillary level. Here, we present data showing that
capillary dilation is also partly mediated by signalling via astrocytes. Electrically stimulated
neuronal activity in cortical slices resulted in a capillary dilation of 20.3±3.5%. A selective
inhibitor of prostaglandin E2 receptor 4, L(p=0.004). When nearby astrocytes were patch-clamped and filled with 30 mM BAPTA
(resting [Ca2+]i=24nM) to buffer [Ca2+]i in astrocytic endfeet along the vessels, stimulationevoked dilation was reduced by 64%. Preliminary data from immunolabelling experiments
show that prostaglandin E synthase is present in astrocytic endfeet, suggesting them to be a
likely location for prostaglandin E2 synthesis from AA and its subsequent release onto
capillary pericytes. Further work is needed to elucidate how astrocytes sense neuronal
activity and the signalling cascade within astrocytes that leads to prostaglandin E2 release.
Given that capillary non-reperfusion is largely responsible for post-ischaemic tissue damage,
understanding the signalling mechanisms between neurons, astrocytes and pericytes in
regulating cerebral microcirculation may point to future therapies in stroke management.
This work was funded by the Fondation Leducq, the Wellcome Trust and the ERC.
30. SOPHIE NYBERG - UCL DEPARTMENT OF CHEMISTRY
POSTER TITLE
Investigating the mechanisms of LRP1-mediated transcytosis of polymersomes across the
blood-brain barrier.
AUTHORS
Nyberg S, Tian X, Battaglia G
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
ABSTRACT
Polymersomes are amphiphilic nano-scaled vesicles formed via self-assembly in water.
Intracellular delivery of a variety of agents has been extensively demonstrated using these
biocompatible carriers. Previous work in our lab has shown that intravenously administered
Angiopep-2-conjugated polymersomes in mice cross the blood-brain barrier (BBB). We
hypothesised receptor-mediated transcytosis to be the mechanism by which polymersomes
cross the BBB. LRP-1 and polymersome interaction in vitro was confirmed via
immunocytochemistry, with strong co-localisation seen as early as a few minutes after
incubation. In an in vitro transwell BBB model, intracellular uptake of Angiopepfunctionalised polymersomes in endothelial cells was rapid and transient, with fluorescence
peaking at 30 minutes while becoming negligible after 3 hours. Surprisingly, little to no colocalisation was observed between polymersomes and different endocytosis pathway
markers Rab5, Rab7, Rab11 and LAMP1. Furthermore, polymersome transcytosis came to
a complete halt in the presence of N-ethylmaleimide, known to inhibit part of the SNARE
complex. In summary, we have demonstrated transcytosis of Angiopep-conjugated
polymersomes in an in vitro BBB model by receptor-mediated but non-acidifying pathway, in
which the SNARE complex is implicated as essential machinery.
31. MAITE OGUETA GUTIERREZ - UCL DEPARTMENT OF CELL AND
DEVELOPMENTAL BIOLOGY
POSTER TITLE
Circadian clock resetting via non-canonical Rhodopsin signalling and the zona pellucida
protein Quasimodo
AUTHORS
Ogueta-Gutierrez M, Bradlaugh A, Buhl E, Hodge J, Stanewsky R
ABSTRACT
Circadian clocks regulate multiple aspects of animal behaviour and physiology to occur at
optimal times within the 24-h day. In order to do this, they must be accurately synchronized
to rhythmic environmental cues such as light and temperature. In mammals and
invertebrates synchronisation to environmental light:dark cycles occurs via visual and nonvisual pathways. In Drosophila, synchronization is mediated both by the compound eyes,
and by the blue-light photoreceptor Cryptochrome (Cry), present in many but not all of the
clock neurons. Cry undergoes a light-induced conformational change that allows it to bind to
the clock protein Timeless (Tim) and the F-box protein Jetlag (Jet), which results in both the
degradation of Tim and Cry and the re-setting of the molecular clock. However, in the
absence of Cry and retinal photoreception, some pacemaker neurons still retain the ability to
regulate Tim levels in response to light and to reset their clock.
The clock controlled gene quasimodo (qsm) encodes a GPI-anchored zona pellucida protein
that acutely responds to light via a Cry-independent mechanism. Qsm mutants interfere with
the light-dependent degradation of the clock proteins Tim and Period (Per), which results in
abnormal behavioural rhythmicity in constant dim light (LL)
32. FABIAN PETERS - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
The effects of demyelination on mitochondrial dynamics in the saphenous nerve in vivo
AUTHORS
Peters F, Sajic M, Duchen M, Smith KJ
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
ABSTRACT
Demyelination is a pathological condition which is believed to cause profound changes in the
energy demand of axons. While a growing body of evidence suggests that mitochondria
accumulate in the demyelinated portions of axons, much less is known about how this
occurs, and the effects of demyelination on mitochondrial dynamics. Two recent studies
indicate that preventing the accumulation of stationary mitochondria may be acutely harmful
(Ohno et al., 2014), but chronically protective in a dysmyelinating model (Joshi et al., 2015).
We have investigated the effect of demyelination (lysolecithin) on mitochondrial transport
and function in the saphenous nerve in vivo. Mitochondrial movement in myelinated and
demyelinated axons was quantified on days 4, 8, 12, and 20 after lesioning. Mitochondrial
membrane potential was assessed using TMRM and electrical stimulation was applied to
increase mitochondrial trafficking (Sajic et al., 2013). Mitochondrial transport was
significantly reduced in demyelinated axons on days 4 and 8, which coincides with the onset
of electrical excitability of the demyelinated axolemma (Smith et al, 1982) and returned to
baseline between days 12 and 20, coincident with remyelination. We conclude that this
reduction in mitochondrial transport may contribute to the late-onset axonal degeneration
found in peripheral demyelinating diseases.
33. FATEMAH SAFAR - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
The effect of propofol on human hyperekplexia mutant α1β GlyR
AUTHORS
Safar F, Lape R, Yu R, Biggin P, Sivilotti L
ABSTRACT
The glycine receptor (GlyR) is a Cys-loop ligand-gated chloride channel that mediates fast
synaptic inhibition in brain and spinal cord. Heritable malfunction of glycinergic transmission
in man causes hyperekplexia, a neuromotor disorder characterised by exaggerated startle
responses to normal sensory stimuli. Many mutations responsible for the disease are found
in GlyR subunits, where they highlight residues essential for channel activation.
We evaluated the effects of three human hyperekplexia α1 subunit mutations, S231N,
Q266H and S267N, on human α1β GlyR expressed in HEK293 cells. Glycine dose-response
curves obtained by whole-cell patch-clamp confirmed previous reports (Bode & Lynch, 2014)
that these mutations decrease the channel sensitivity to glycine.
Single-channel recording showed that the maximum open probability (Popen ) reached by
mutant channels was much lower than that of wild type GlyRs (0.37 – 0.64 cf. 0.98). This
suggests that the human hyperekplexia mutations tested here strongly reduce gating
efficacy.
To determine whether the function of the mutant GlyRs can be rescued, propofol was used.
Propofol (50 µM) was found to enhance responses to submaximal glycine concentrations in
all receptors (by 2.76 - 5.13-fold). The maximum response produced by glycine was
increased by propofol only for the S231N mutant GlyR.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
34. SANDRA SELJESET - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Profiling an inhibitory neurosteroid at GABAA receptors
AUTHORS
Seljeset S, Smart T
ABSTRACT
The GABAA receptor is the main mediator of inhibitory neurotransmission in the central
nervous system. GABA controls neuronal excitability by activating two different modes of
inhibition: synaptic receptors mediate fast, transient phasic inhibition, whereas peri- and
extra-synaptic receptors maintain a lower but more persistent level of inhibition. The activity
of the GABAA receptor is regulated by an array of endogenous signalling molecules that act
by either directly modulating the receptor or by affecting the presynaptic release of GABA. Of
these, the endogenous neurosteroids are the most potent and can either potentiate or inhibit
GABAA receptor function.
Here we study the inhibitory neurosteroid, pregnenolone sulphate (PS), and explore its
functional profile with neuronal GABAA receptors and with typical synaptic and extrasynaptic
recombinant GABAA receptors expressed in HEK cells. PS exhibits minimal receptor
subtype selectivity, but displays use-dependence. PS inhibits steady-state whole-cell GABA
currents more so than peak currents, in accord with a role for PS in modulating neuronal
tonic currents. Despite its use-dependence, antagonism by PS showed little voltagedependence and did not compete with the open-channel blocker picrotoxinin for a binding
site, indicating that PS probably does not act by blocking the GABA channel.
35. TERRI STEPHEN - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Miro1 regulates activity-driven positioning of mitochondria within astrocytic processes
apposed to synapses and is essential for intracellular calcium regulation
AUTHORS
Stephen TL, Higgs NF, Kittler JT
ABSTRACT
Activity-dependent positioning of mitochondria within neurons ensures that energy supply
and calcium buffering requirements are matched to the demands of neuronal signalling.
Although the specific mechanisms that govern mitochondrial trafficking and positioning in
astrocytes remain unresolved, it is fast emerging that maintaining mitochondrial function is
important for regulating astrocyte function. Using live confocal microscopy of primary
cultures and organotypic brain slices, we observed that mitochondria are mobile under basal
conditions in astrocytes. We find that enhancing neuronal activity induced mitochondrial
remodelling, with a concomitant reduction in mobility, dependent on calcium entry and
mediated by NMDA receptors. Stimulating neuronal activity also induced mitochondrial
confinement within astrocytic processes near synapses. Further, we observed that the
calcium-sensing domains of the mitochondrial Rho-GTPase protein 1, Miro1, are important
for regulating mitochondrial trafficking dynamics in astrocytes and are required for their
activity-driven confinement near synapses. Therefore, this study provides a mechanism for
spatially regulating mitochondria in astrocytic processes involving Miro1. The EF-hands of
Miro1 also appear to have important consequences for intracellular astrocyte calcium
35
2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
regulation and potentially calcium wave propagation. Downstream, the ability of astrocytes to
spatially regulate energy production and calcium-buffering could have important
consequences for gliotransmission and ultimately neuronal function.
36. ALEKSANDRA TOPCZEWSKA - UCL SCHOOL OF PHARMACY
POSTER TITLE
The role of T-type Cav3.2 channels in influencing neuronal activity in entorhinal cortical
stellate cells
AUTHORS
Topczewska AP, Dolphin AC, Shah MM
ABSTRACT
The medial Entorhinal Cortex (MEC) is situated between the neocortex and hippocampus. It
plays an important role in spatial navigation (Hafting et al., 2005) and memory (Hasselmo,
2006). The layer II stellate cells of the MEC (LIISCs), particularly, have been implicated to be
involved in spatial navigation. Interestingly, the intrinsic membrane properties of these
neurons differ across the dorso-ventral axes of the LIIMEC (Nolan et al., 2007; Garden et al.,
2008; Giocomo et al., 2007). This is likely to be due to a difference in ion channel expression
and properties. In my study, I have investigated whether the T-type, Cav3.2 Ca2+ channels
contribute towards this LIISC intrinsic membrane property, the dorso-ventral gradient. My
results show that the dorso-ventral gradient in the input resistance, the resting membrane
potential and the number of evoked action potentials, which is, present in LIISCs Cav3.2 wild
type cells, is significantly reduced in Cav3.2 null mice. These results indicate that T-type
Cav3.2 channels play a part in establishing the LIISC intrinsic membrane dorso-ventral
gradient. Further investigation is required to understand the mechanisms by which Cav3.2
channels regulate the intrinsic membrane properties of the LIISCs.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Cognition and Behaviour | Elvin Hall
37. GERGO BOHNER - GATSBY COMPUTATIONAL NEUROSCIENCE UNIT AT UCL
POSTER TITLE
Automated calcium signal extraction from two-photon microscopy recordings
AUTHORS
Bohner G, Pachitariu M, Marshel J H, Deisseroth K, Sahani M
ABSTRACT
Large-scale imaging of fluorescent calcium reporters has become the method of choice for
monitoring neural activity within large populations. However, automated identification and
recovery of calcium signals from individual cells remains challenging: very few data
incorporate activity-independent anatomical markers to identify single cells and the dense
packing of neurons may lead to cell bodies overlapping within images.
We present a new approach to this problem that exploits the stereotypy of somatic images
and the broad coherence of activity-related fluorescence within a cell. We optimise a
dictionary of shape elements that combine to describe both the mean shape of each cell and
its covariant modulation. The algorithm iterates between cell identification (using a novel
variant of matching pursuit that pursues weighted subspaces within both the first and second
moments of the image sequence) and updating the dictionary elements (using a block-based
variant of K-SVD). After convergence, single-cell signals are obtained by projection into the
weighted subspaces identified during the final pursuit. Further similar data can be
segmented very rapidly without the need for further learning. As the method learns
constraints on the spatial extent and shape of extracted objects, it naturally segments
overlapping cells with signal contamination minimised by the implicit orthogonalisation of
matching pursuit.
Evaluation of automated signal extraction algorithms is hampered by the lack of objective
quality measures. We collected functional data from mouse visual cortex combining
spontaneous and full-fieldgrating stimulated activity to derive a novel metric for signal
recovery based on coherence of orientation tuning. Without manual pre- or post-processing,
the algorithm returned cellular signals that show high correlation with manually extracted
examples, significant cellular stimulus tuning and homogeneous tuning of individual pixels
within the region of interest.
38. ALEXANDER F BROWN - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Screening study of SCA-Negative ataxia patients for presence of Friedreich’s ataxia
trinucleotide expansion mutation
AUTHORS
Brown AF, Parkinson MH, Mudanohwo E, Labrum R, Sweeney M, Giunti P
ABSTRACT
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Background: Patients presenting with ataxia are tested for expansion mutations in genes for
the common spinocerebellar ataxias, but not Friedreich’s ataxia (FRDA) unless requested.
Since the discovery of the frataxin (FXN) gene, atypical cases of FRDA have been identified.
We therefore questioned whether the root of many apparently idiopathic ataxia cases could
be the FRDA mutation.
Aims: To determine the incidence of FRDA in a cohort of 1768 ataxia patients referred for
the Friedreich’s ataxia genetic test, and 1997 not referred. This study represents the largest
of its kind. These findings will allow us to better define the status FRDA testing should hold
in ataxia patient screening.
Methods: Triplet-primed PCR was used to detect expansion presence. If discovered, longrange PCR was performed to distinguish FRDA-positives. Carriers were screened for point
mutations and exonic deletions. Obtaining clinical information allowed a genotype-phenotype
correlation in positive cases.
Results: Out of 1768 ataxia patients referred for the FRDA test, 207 (11.7%) were FRDA
positive, and 29 were confirmed carriers (1.6%). Out of 1997 ataxia patients not referred for
the FRDA test, 3 were FRDA positive (0.15%), 11 were carriers for the FRDA expansion and
5 DNA samples were degraded. The three FRDA positive patients displayed an atypical,
late-onset phenotype. The point mutation and exonic deletion screening for the 11 carriers is
underway.
Conclusion: These results provide evidence that an atypical FRDA phenotype is very
unusual among patients presenting with ataxia, and support use of the FRDA test only if
recommended by the patient’s neurologist.
39. JOANNE FALCK - UCL SCHOOL OF PHARMACY
POSTER TITLE
Reconstructing cells of the CA1
AUTHORS
Lange S, Falck J, Mercer A, Thomson A
ABSTRACT
Within the brain simulation component of the EU Human Brain Project, our laboratory is
providing and producing 3D reconstructions of neurones in the CA1 hippocampus and
parallel electrophysiological recordings. These data are being processed from an archive of
adult rat hippocampus collected for over 20 years.
Paired recordings using sharp electrodes (filled with KMeSO4 and biocytin) from acute slices
provide information on the electrophysiological properties of the cells and their connections.
Subsequent resectioning and HRP reaction to reveal the biocytin visualises the morphology
of the recorded cells.
Cells for reconstruction are being selected for the quality of the cytochemical processing and
the availability of the corresponding electrophysiological data.
The majority of interneuronal types of the CA1 have been identified. These have been/are
currently being reconstructed at 100x magnification in 3D using the Neurolucida software.
Three putative sub-classes of pyramidal cells have also been identified. These indicate a
variation in the positioning of the soma in stratum pyramidale (SP) and in the branching
pattern of the apical dendrite.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
40. JANOSCH HELLER - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Super-resolution microscopy to study the subcellular distribution and trafficking of astroglial
receptors
AUTHORS
Heller JP, Rusakov DA
ABSTRACT
Besides physically structuring the brain astrocytes play an active role in shaping and
maintaining neuronal circuits. Astrocytes regulate neuronal activity and synaptic
transmission and plasticity through the secretion and absorption of neurotransmitters.
Especially their release of activators and co-activators of neuroreceptors is important in the
functioning brain. Astrocytes constantly sense the surrounding milieu, act upon changes in
extracellular ion concentrations and undergo plasticity. Astrocytes change their morphology
and protein expression affecting calcium activity in the cells as well as gliotransmitter release
which can shape synaptic activity and neuronal excitability. The plasticity of astrocytes can
be induced by neuronal activity predicting a constant interaction between neurons and glial
cells. Synaptically released glutamate triggers astrocytic Ca2+ responses via the activation
of astrocytic metabotropic glutamate receptors. This causes the calcium-mediated release of
gliotransmitters such as glutamate and ATP which thus modulates the excitability of adjacent
neurons. We want to employ super-resolution microscopy techniques such as PALM
(photoactivated localization microscopy) to visualise the dynamics of clusters of
metabotropic glutamate receptors in astrocytes. PALM relies on the sequential activation,
imaging and bleaching of a sparse subset of fluorescent molecules, either photoactivatable
proteins or photoswitchable fluorophores. With this method, images can be obtained with
sub-diffraction resolution by localizing individual activated molecules in each frame. Using
PALM, clusters of the receptors can be imaged and the number of receptor molecules can
be counted. Additionally, the position of each photo-converted molecule can be tracked for a
short period of time before photobleaching which allows the generation of trajectories of
several well separated molecules over a given period of time which provides a random
sampling of hundreds of trajectories. Thus, the recruitment of metabotropic glutamate
receptors from intracellular vesicular stores and the diffusion within the plasmamembrane
can be monitored. Furthermore, we want to use photostimulation methods such as
glutamate uncaging and optogenetics to manipulate the excitation of neurons and astrocytes
in the network. Experiments will be performed on a single cell level and in acute as well as
organotypic slices to evaluate the influence of the maturation of circuits.
41. RAJVINDER KARDA - UCL INSTITUTE FOR WOMEN’S HEALTH
POSTER TITLE
Generation of light-emitting somatic-transgenic mice for disease modelling of Hypoxic
Ischaemic Encephalopathy
AUTHORS
Karda R, Delhove JMKM, Buckley SMK, Rahim AA, Rocha-Ferreira E, Perocheau D, Ng J,
R Mckay TR, Hagberg HH, Johnson MR, Waddington SN
ABSTRACT
In this study, we aimed to deliver NFkB activated or SFFV (constitutive) promoter driven
codon optimised luciferase reporter constructs to brains of neonatal mice to quantitate
astrogliosis and inflammation in a mouse model of Hypoxic Ischemic Encephalopathy (HIE).
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Lentivirus vectors possessing different envelope configurations were injected intra-cranially
into CD1 outbred neonatal (P0) mice, and luciferase expression was monitored continuously
by whole body bioluminescence imaging of conscious mice before and after induction of HIE
by carotid artery ligation followed by exposure to hypoxia (P7).
The two pseudotypes gp64 and VSV-g exhibited different cellular tropisms within the central
nervous system; VSV-g predominantly targeting neuronal cells whereas, gp64 transducing
cells of astrocytic morphology. We observed a significant correlation between the luciferase
expression 24 hours after surgery and weight 7 days after surgery in mice which had
received the gp64 pseudotyped NFκB (P = 0.0007) or SFFV (P = 0.0231) biosensor; the
most severely affected HIE mice had the lowest luciferase expression and weight. However,
the HIE mice which had received the VSV-g pseudotyped NFκB or SFFV biosensor failed to
show such correlation. This indicates that gp64-controlled luciferase expression in astrocytes
is predictive of brain injury 24 hours after surgery.
42. CAITRIONA O'ROURKE - UCL EASTMAN DENTAL INSTITUTE
POSTER TITLE
Tissue engineered 3D co-cultures as models of the nervous system
AUTHORS
O'Rourke CM, Lee-Reeves C, Phillips JB
ABSTRACT
Our research uses tissue engineering technology to organise nervous system cells within
hydrogels to create physiologically relevant engineered neural tissue equivalents. The
models resemble functional nervous system tissue, with aligned tracts of neurons and glia
arranged within a robust collagen hydrogel.
This approach, unlike more traditional cultures or those that use stiff 3D matrices or more
chemically complex hydrogels, enable neural cells to behave like their in vivo counterparts.
For example, glial cells can adopt a less reactive phenotype reminiscent of the undamaged
CNS. When stimulated with a damage cue, they undergo reactive gliosis and mimic the
cellular and molecular responses characteristic of CNS injury. Neuronal survival, phenotype,
neurite outgrowth, degeneration and electrophysiology can be studied. Furthermore, neuronglial interactions such as myelination can be recreated.
Artificial neural constructs can be made using simple cell populations or more complex
mixtures of neurons and glia according to requirements, and they can be aligned and
stabilised, providing a robust and reproducible environment that is highly controllable and
compatible with a wide range of cell and molecular analysis techniques. This simple,
consistent and physiologically relevant model system, which uses a multi-well plate format
can potentially be used at a scale suitable for commercial R&D.
43. PHONG PHAN - UCL MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING
POSTER TITLE
Spatial distribution of changes in oxidised cytochrome c oxidase during visual stimulation
using broadband spectroscopy imaging
AUTHORS
Phan P, Highton D , Tachtsidis I, Brigadoli S, Elwell C
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
ABSTRACT
Changes in concentration of oxidised cytochrome c oxidase (Δ[oxCCO]) can be used as a
marker for oxygen consumption and utilisation in tissue. In this poster, a method will be
presented for investigating the spatial distribution Δ[oxCCO] during functional activation.
Continuous Near-Infrared Spectroscopy (NIRS) measurements were recorded using a
Broadband NIRS System with an array consisting of 4 source locations surrounded by 14
detector locations. The array was centred over Oz according to 10/20 EEG location so as to
measure changes in concentration of oxyhaemoglobin (Δ[HbO2]), deoxyhaemoglobin
(Δ[HHb]) and Δ[oxCCO] in the visual cortex during visual stimulation. The stimulus was a
4Hz flickering semi-circular checkerboard pattern, aiming to stimulate only the left or the right
visual cortex. 10 epochs were presented for each half of the visual cortex, each consisting of
20s of stimulation and 20s of rest. This was repeated for each source location of the array.
Δ[HbO2] and Δ[HHb] consistent with functional activation were seen during visual
stimulation. There was a preferential response of Δ[oxCCO] to stimulation on the
contralateral field and a graded response of Δ[oxCCO] across the stimulated cortex which
can be used to create functional images of oxCCO over the visual cortex.
44. ROMAN RODIONOV - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
EpiNav(TM) - novel software to guide neurosurgical treatment of epilepsy
AUTHORS
Rodionov R, Zombori G, Nowell M, Sparks R, Miserocchi A, Micalef C, Wehner T, Diehl B,
Mcevoy AW, Ourselin SGR, Duncan JS
ABSTRACT
We created the novel software EpiNav(TM) which is dedicated to support the presurgical
pathway of patients with epilepsy, incorporating results of 3D multimodal neuroimaging data
(MRI, fMRI, DTI, EEG-fMRI, MEG/EEG source imaging, CT, PET, SPECT).
Results: EpiNav(TM) software is implemented in clinical practice at the National Hospital for
Neurology and Neurosurgery (London, UK).
EpiNav(TM) supports the planning of the placement of intracranial electrodes that are
inserted into the brain to identify the source of epilepsy and which may be surgically
removed. This is a two-stage process, with initial formulation of the strategy of areas to be
sampled with depth electrodes, followed by the precise planning of the electrode trajectories.
The computer-assisted planning implemented in EpiNav(TM) takes 15 minutes compared
with 3-4 hours required for the standard manual process to plan 12-16 electrode trajectories
in an individual patient.
EpiNav(TM) is also useful for planning the resection after delineation of the epileptogenic
zone, in combination with the display of eloquent and critical structures.
Conclusions: EpiNav(TM) has evolved into an indispensable tool supporting the decisions in
diagnostic and operative stages of epilepsy surgery, saving time for the healthcare team and
increasing the precision and safety of interventions.
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45. DERVIS SALIH - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Identifying the earliest molecular and gene expression changes associated with rising
amyloid-beta in transgenic mice
AUTHORS
Salih DA, Cummings DM, Liu W, Bayram S, Yasvoina M, PorteliusE, Matarin M, Richardson
JC, Hardy JA, Edwards FA
ABSTRACT
Objectives: By the time cognitive deficits are first detected in patients with Alzheimer’s
disease (AD) around 20% of the hippocampus has already been lost. Attempting to treat the
disease at this late stage may be why clinical trials have not been successful. The objective
of this study is to identify the earliest molecular changes that take place in mouse models of
elevated Abeta.
Methods: We use the Mouseac database (www.mouseac.org) that compares gene
expression changes and histology, in the hippocampus, cortex and cerebellum at four ages,
in four Amyloid mouse models, transgenic for familial mutations of APP and/or PSEN1. We
use bioinformatics to identify the earliest genes/pathways altered during disease
progression. In parallel, we use mass spectrometry and electrophysiology.
Results: Even before plaques develop in APP/PSEN1 transgenic mice we detect differences
in synaptic transmission as early as 2 months of age, concomitant with the rise of Abeta-42
levels. Our genome wide expression data and co-expression network analysis reveals
synaptic transmission also as the most significant gene module, and highlights several
genes of interest that may provide novel targets.
Conclusions: Identifying the earliest changes that occur during the progression of
Alzheimer’s is essential for developing early interventions before neurodegeneration
becomes irreversible.
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Cognition and Behaviour | Elvin Hall
46. VINCENT ADAM - GATSBY COMPUTATIONAL NEUROSCIENCE UNIT
POSTER TITLE
Pre-perceptual grouping of auditory scenes explains contextual biases in the perception of
ambiguous tonal shifts.
AUTHORS
Adam V, Chambers C, Pelofi C, Pressnitzer D, Sahani M
ABSTRACT
Auditory Perception is influenced by recent sensory history. Perception of ambiguous tonalshifts can be biased by a previous context (Chambers et al, submitted). In this study stimuli
were Shepard Tones, i.e. octave-related components of a base frequency, with a Gaussian
spectral envelope (Shepard. 64). When judging the direction of shift between two such
complexes T_1 and T_2, listeners report the shorter path between components (distance in
log frequency). When T_2 components are equidistant from adjacent T_1 components (halfoctave interval), this cue is removed and listeners report either an upward or downward shift
with equal probability. Biases are introduced by preceding ambiguous pairs with contextual
complex tones (C). The authors found that the pitch shift between T_1 and T_2 was strongly
influenced by the frequency region of C, in a way that the shift encompassed the frequency
region of C. We suggest that the biasing of the perceived shift of those shift-ambiguous pairs
arises as a consequence of an underlying general pre-perceptual grouping mechanism
attributing spectro-temporal components of an auditory scene to ongoing 'tracks' based on
spectro-temporal continuity. At the level of individual tracks, local frequency shift can be
extracted and combined to give rise to a global shift percept. This model solves a
fundamental attribution problem: how to bind spectro-temporal components in a useful way
given the statistics of natural sounds. Applied to the artificial stimuli of the experiment,
components of T_1 and T_2 are attributed to ongoing tracks built from the context. The
position of these tracks before the pair bias the attribution of their components and hence
the locally extracted frequency shift. Our model reproduce psychophysical results in both
ambiguous and non-ambiguous cases and in both the presence or absence of context. In
both this model and in psychophysical data, past exposure only influence behaviour in
ambiguous conditions which is the key condition enabling to highlight this underlying
mechanism in action.
47. JESSICA AYLWARD - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
The impact of threat of shock induced stress on cognition
AUTHORS
Aylward J, Roiser J, Robinson OJ
ABSTRACT
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Stress has long been thought to be a precipitating factor in mood and anxiety disorders, with
some individuals particularly vulnerable to stress. Classical diagnoses rely on asking an
individual how they react to stress; in this study we attempt to quantify this in a nonsubjective fashion by exploring the impact (on reaction time/accuracy) of experimentallyinduced stress on a simple neurocognitive task (previously shown to be sensitive to threat of
shock). Threat of unpredictable shock is a translational, within-subject, stress induction that
can induce neurobiological states associated with pathological anxiety (Robinson et al
2012). The stability of these stress-induced changes was assessed in a healthy sample on
two separate testing sessions separated by about 13 days.
We replicate prior work demonstrating improved inhibitory control (i.e. no-go accuracy) under
threat of shock (Robinson et al., 2013), but expand these findings to demonstrate that slower
reaction times to go trials under threat (perhaps driven by increased non-decision - i.e. motor
and perception - time) may be a reliable measure of individual anxious responding. This
paradigm may therefore hold promise as a non-subjective and stable trait measure of stress
responding that can be used as an index of mood and anxiety disorder vulnerability.
48. SARAH BUCK - UCL INSTITUTE OF CHILD HEALTH
POSTER TITLE
Material-specific effects of side of resection on recognition after surgery for temporal lobe
epilepsy
AUTHORS
Buck S, Isaacs E, Baldeweg T, Polkey CE, Mishkin M, Vargha-Khadem F
ABSTRACT
Purpose: We investigated verbal and visual recognition in a group of patients who underwent
surgery for temporal lobe epilepsy. The aims were to examine the effects of material (words;
faces) and side (left; right), and age at onset of epilepsy on recognition memory.
Method: Fifty-six patients (32 left; 24 right temporal excisions; mean age 31 years, range 1249) participated. Age at onset of epilepsy (ranged 4 months -30 years), age at surgery
(range 13 to 46 years), and duration of epilepsy (ranged 2-45 years) were recorded.
Recognition memory was assessed using the Warrington’s word and face test.
Results: There was a significant interaction between side of resection and material-type
(p<0.001), with verbal recognition more impaired after left than right, and visual recognition
more impaired after right than left-sided surgery. Age at onset of epilepsy was correlated
with verbal recognition after left (p=0.001), but not after right temporal resection. Neither
age at surgery, nor duration of epilepsy correlated with recognition.
Conclusion: There is a double dissociation with verbal recognition more impaired after left,
and visual recognition more impaired after right temporal removals. Earlier age at onset of
left-sided epilepsy is associated with better verbal, but not visual recognition.
49. WING YEE CHOW - UCL PSYCHOLOGY AND LANGUAGE SCIENCES
POSTER TITLE
To predict, or not to predict? An investigation into prediction inhibition during language
comprehension
AUTHORS
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Chow WY, Baptist M, Murphy E
ABSTRACT
Previous research has shown that we use rich contextual information to anticipate upcoming
input as we process language in real time. Language processing is facilitated when our
predictions are correct, and signals that our predictions might be wrong are quickly detected.
Previous research has shown that comprehenders engage predictive mechanisms when
they process wh-dependencies (e.g., “Which plumber did the landlord hire?”) in real time.
Recent event-related potentials (ERPs) evidence suggested that comprehenders can
immediately use the lexical meaning of the arguments (e.g., “plumber” and “landlord”) to
predict an upcoming verb (e.g., “hire”), but their verb predictions are initially blind to the roles
of the arguments (Chow, Smith, Lau & Phillips, submitted). Further, previous studies have
shown that the processing of wh-dependencies respect detailed grammatical constraints
(e.g., “book” cannot be interpreted as the direct object of “write” in “Which book did the
historian who wrote read last year?”). We will present preliminary findings from two reading
eye-tracking and ERP experiments that examine the potential role of prediction inhibition in
comprehenders’ online sensitivity to detailed grammatical constraints.
50. CAMILLA CLARK - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Musical rules and reward in dementia
AUTHORS
Clark CN, McCallion O, Golden HL, Nicholas JN, Cohen MH, Mummery CJ, Schott J,
Warren JD
ABSTRACT
Responses to music depend on internalised musical ‘rules’ that generate strong
psychological expectancies. We assessed cognitive expectations generated while listening
to music and associated affective responses in cohorts of patients with Alzheimer’s disease
(AD) and canonical syndromes of frontotemporal lobar degeneration (behavioural variant
frontotemporal dementia (bvFTD), semantic dementia and progressive nonfluent aphasia
(PNFA)) in relation to healthy older individuals. We created a set of short novel melodies
manipulating cadence such that the melodies sounded either ‘finished’ or ‘unfinished’.
Participants labelled each melody explicitly as finished or unfinished and to rate how
pleasing they found the ending.
Relative to the healthy control group, only the PNFA group showed a significant deficit of
cognitive labelling of melodies as finished or unfinished; while all patient groups apart from
the AD group found unfinished melodies significantly more pleasant and all patient groups
apart from the bvFTD group found finished melodies significantly less pleasant than healthy
controls. Comparing patient groups, the PNFA group found unfinished melodies significantly
more pleasant than both the AD group and bvFTD group.
Our findings suggest that musical rules and reward are differentially impaired in dementia
syndromes and dementias may selectively degrade the pleasure we derive from music
51. FLEUR CORBETT - UCL PSYCHOLOGY AND LANGUAGE SCIENCES
POSTER TITLE
Joining the dots in motion perception: what are the consequences of dorsal stream
vulnerability?
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
AUTHORS
Corbett F, Atkinson J, Braddick O, Swettenham J
ABSTRACT
Impaired motion sensitivity has been found in a range of developmental disorders, reflecting
reduced dorsal stream functioning. What are the consequences of this dorsal stream
vulnerability? The current study explored the relationship between motion sensitivity and
motor competency using novel visuomotor integration tasks and analogous perceptual tasks.
Both typical adults and adults with poor motor competency (Developmental Coordination
Disorder) were assessed (N=60) and all participants had normal or corrected-to-normal
vision. Stimuli were static or dynamic rotary random dot patterns with consistent speed, dot
density and viewing distance. Participants were asked to reach and touch the rotary pattern
centre (visuomotor task) or make a key-press to indicate the location of the rotary pattern
centre (perceptual task) at four coherence levels (12.5; 25; 50; 100%).
Both form and motion sensitivity improved with coherence. Sensitivity was selectively better
on the visuomotor task than the perceptual task for dynamic stimuli only, suggesting that
motion information has preferential access to visuomotor control. This is concordant with the
notion that global motion processing and visuomotor control are both dorsal stream
properties. Adults with DCD had poorer motion sensitivity and the relationship with motor
competency is explored here, with reference to dorsal stream functioning across
developmental disorders.
52. ANNA DZIECIOL - UCL INSTITUTE OF CHILD HEALTH
POSTER TITLE
Mapping the extra-hippocampal damage in developmental amnesia
AUTHORS
Dzieciol A, Bachevalier J, Gadian D, Saleem K, Saunders R, Clark C, Mishkin M, VarghaKhadem F
ABSTRACT
Patients with developmental amnesia (DA) experience a profound episodic memory loss
associated with hypoxia-induced bilateral hippocampal atrophy. Here, we provide a further
anatomical characterisation of DA by exploring damage outside of the hippocampus in a
group of 17 patients, in comparison with an equal number of controls. The extent of injury
was investigated using: (i) voxel-based morphometry, (ii) manual and automatic
segmentation of structure volumes and (iii) tract-based spatial statistics. Tests of intelligence
and memory were also administered. Results showed that in addition to hippocampal
damage, patients with DA had severe atrophy of the mammillary bodies, mild volume
reduction of the thalamus, and widespread loss of white matter structure. White matter
integrity across the whole brain was related to patients’ intelligence, but not to their memory,
and integrity of the ventral cingulum predicted performance on tests of recognition. In
addition, thalamic volumes were correlated with patients’ visual memory function. Together,
these results show that extra-hippocampal abnormalities may contribute to the cognitive
outcome of patients with DA, independent of the hippocampus. The mechanisms and time
course of this extra-hippocampal damage remain to be determined.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
53. PAUL FORBES - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Testing the social top-down response modulation (STORM) model using virtual reality
AUTHORS
Forbes P, Pan X, Hamilton A
ABSTRACT
Background: The social top-down response modulation (STORM) model suggests mimicry
changes depending on the social context.
Aims: The current study aimed to test this model using a virtual reality paradigm by seeing
whether the amount of social engagement displayed by an avatar modulated participants’
mimicry.
Methods: Participants observed two avatars move their index finger to a series of targets
and afterwards were instructed to move to the same targets. The speed (fast/slow) and
height (high/low) of the avatars’ movements was manipulated. One avatar was socially
engaged (e.g. smiled at participants) whereas the other was socially disengaged (e.g. was
busy watching a screen).
Results: Despite participants being instructed only to copy the goal of the observed action,
participants were sensitive to the kinematics of the avatars’ movements in both conditions
(i.e. they mimicked the avatars). For example, on trials where the avatar moved with a high
trajectory between the targets, participants also tended to move with a high trajectory,
compared to trials where the avatar moved with a low trajectory. Importantly, this mimicry
was enhanced when the avatar was socially engaged.
Conclusion: These findings are consistent with the STORM model: mimicry is enhanced
when the observed actor is socially engaged.
54. PEDRO HENRIQUES - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Neural correlates of selective visual attention in zebrafish
AUTHORS
Henriques PM, Jackson S, Bianco I
ABSTRACT
Animals use attentional mechanisms to focus computational resources towards
behaviourally relevant stimuli, at the expense of less relevant competitors. The mechanisms
by which attention is allocated are thought to rely on both the stimuli’s intrinsic features and
their value to the animal’s current behaviour, but despite the long interest in attention, much
is still unknown about the neural populations and network dynamics that underlie this
process.
We are studying attentional mechanisms in the context of larval zebrafish’s hunting
responses, a visually guided, goal-directed behaviour. We have developed a virtual-reality
closed-loop assay in which visual stimuli are presented to tethered larvae in combination
with live tracking of prey-catching responses. By systematically varying visual stimulus
parameters, we show that prey-catching is selective for conjunctions of visual features. This
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
analysis will form the basis for a selective attention assay in which competing stimuli, with
different values, are presented to larvae while neural activity is simultaneously monitored
using two-photon imaging. We have also begun to characterise a midbrain nucleus thought
to be involved in selective attention, the nucleus isthmi. We find that it is composed of two
subpopulations of cholinergic neurons, which might be differentially involved in modulating
sensorimotor processing in the optic tectum.
55. SOMYA IQBAL - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Contextual influences on risk based decision making and reward value
AUTHORS
Iqbal S, Rigoli F, Dolan JR
ABSTRACT
Influential theories propose that the brain represents an average reward distribution based
on past reward history. Whether such average reward representation can be formed through
associations with contextual cues remain unclear.
We used a task in which participants (18) chose between a sure monetary gain and a
gamble associated with double that gain and zero, each with 50% chance. The monetary
gain of the certain option varied across blocks of trials and was drawn from one of two
different, but overlapping, reward distributions (high and low value context, respectively).
The context changed rapidly and reward information was shown. This allowed us to test
whether an average reward representation influences behaviour through contextual
associations that can be activated rapidly.
Results showed that participants who gamble more with large amounts also gamble more
when equivalent choices were associated with relatively larger amounts within a context
(low), while participants who gamble more with smaller amounts also gamble more when
equivalent choice were associated with relatively smaller amounts within a context (high).
Our observation of a context effect that emerged rapidly suggests that a representation of
average reward can be formed via associations with contextual cues rather than based on
the past history of reward alone.
56. MEHDI KERAMATI - GATSBY COMPUTATIONAL NEUROSCIENCE UNIT
POSTER TITLE
What leaves leave: information value optimizes the depth of model-based planning
AUTHORS
Keramati M, Smittenaar P, Dolan R, Dayan P
ABSTRACT
Efficiently planning a behavioral strategy requires taking into account all short-term and longterm consequences of each option. However, thinking indefinitely deep into the mental
decision tree is computationally expensive in complicated environments. Here, we propose a
normative framework for computing the optimal depth of planning (value-iteration in a modelbased reinforcement learning system) that trades off accuracy (the deeper, the more
accurate) versus deliberation time. The optimal depth also depends on the precision of prior
believes about the value of each option (e.g., values in a model-free reinforcement learning
system). We then experimentally test the predictions of the model, and show that human
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
subjects limit their depth of planning to a certain level, and that this depth is regulated by the
time-limits they have for planning.
57. POSTER WITHDRAWN
58. LUCIA MAGIS-WEINBERG - UCL PSYCHOLOGY AND LANGUAGE SCIENCES
POSTER TITLE
Neural correlates of the development of the evaluation of social vs. non-social information
during adolescence
AUTHORS
Magis-Weinberg L, Dumontheil I, Custers R, Blakemore SJ
ABSTRACT
Social cognition changes during adolescence influenced by neurodevelopment. In the social
brain, regions involved in understanding other people, activity in the medial prefrontal cortex
(MPFC) decreases with age. There are changes in the executive functions network, in
particular the rostro-lateral prefrontal cortex (RLPFC), that support social cognition, such as
judgement, attention and relational integration. In a developmental fMRI study we probed
brain activation in 39 participants (11–31 years) while they evaluated and manipulated nonsocial (Town) and social information (People). Behavioural results show comparable
response times in adolescents and adults (overall slowest in the Relational manipulation of
Town information). Rating consistency increased with age (higher for non-social). MPFC
activation was greater when participants evaluated social information. ROI analyses within
the MPFC showed that the cluster associated with self-reference had increased recruitment
for the Self condition in the social task. Activation of the relational integration network,
including the RLPFC, was observed in the People and Town tasks. Recruitment of anterior
insula for relational integration in Town task decreased with age. Adolescents increased
recruitment of the anterior cingulate cortex in the Relational condition in the Town task, while
for adults recruitment was greater in the Relational condition of the People task.
59. ELLIOT MURPHY - UCL PSYCHOLOGY AND LANGUAGE SCIENCES
POSTER TITLE
Individuation and abstraction: A neurolinguistic perspective
AUTHORS
Murphy E
ABSTRACT
This poster reviews a number of studies mapping the neural substrates of abstract and
concrete word processing, using them as a guide for mapping brain regions implicated in
copredication. Copredication is the phenomenon of two apparently incompatible properties
being attributed to a single object, creating an "impossible" object (e.g. "The book was
brilliant but weighed a ton"). Licencing conditions on copredication are noted, and the poster
suggests some new directions for exploring the brain regions implicated in conceptual
representations.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
60. SYLVIA PAN - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Using Interactive Virtual Characters in social neuroscience
AUTHORS
Hale J, Pan X, Hamilton A F De C
ABSTRACT
Recent advances in the technical ability to build realistic and interactive Virtual Environments
have allowed neuroscientists to study social cognition and behaviour in virtual reality. This is
particularly useful in the study of social neuroscience, where the physical appearance and
motion of Virtual Characters can be fully controlled. In this work, we present the design,
implementation, and preliminary results of two case studies exploring different types of social
cognition (congruency effect and mimicry) using interactive Virtual Characters animated with
either real-time streamed or pre-recorded motion captured data.
61. ANA MARIA RIVAS - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Anatomical and behavioural changes across the lifespan
AUTHORS
Rivas-Grajales AM, Cappelletti M, Karolis V
ABSTRACT
Background: The age at which cognitive decline begins and which brain structures support
the preservation of certain cognitive abilities remain unclear. Diffusion tensor imaging (DTI),
and in particular fractional anisotropy can be used to address these questions by allowing in
vivo assessment of white matter microstructure.
Aims: To determine how different brain tissue properties of white matter change across the
lifespan, and how these changes are linked to cognitive performance.
Methods: Cognitive profiles and DTI data from 98 healthy participants aged 20-75 years old
were analysed using SPM and FSL. Fractional anisotropy maps were obtained.
Results: We hypothesize that with advancing age, brain integrity is likely to decrease more
notably in prefrontal regions and to correlate with poorer performance in executive functions.
In addition, we expect to see changes in fractional anisotropy appearing much earlier than
changes in cognitive performance.
Conclusions: Changes in brain structure and behaviour across the lifespan are not parallel
processes. This discrepancy might be suggestive of coping mechanisms supported by intact
brain regions. DTI allows us the examination of neural circuitry degeneration associated with
aging which is not possible with other imaging modalities.
62. OLIVER ROBINSON - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
The impact of induced stress on reward and punishment processing during a four armed
bandit task
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
AUTHORS
Robinson OJ, Bond RL, Aylward J, Roiser JP, Dayan P
ABSTRACT
Anxiety disorders are a major worldwide disease burden, but treatment outcomes remain
poor. One major impediment is that current diagnoses are based solely upon subjective selfreport symptoms and not underlying mechanisms. In this study we asked healthy controls
(N=83) to demonstrate (rather than self report) anxious responding by completing a cognitive
task under a within-subject anxiety manipulation. Under alternating periods of threat of shock
and safety, participants completed a 4 armed bandit task comprising independently
fluctuating rewards and punishments. We used a hierarchical Bayesian approach to fit a
reinforcement learning model comprising sensitivity and decay rates for reward, punishment
and choice. Sensitivity parameters demonstrated that subjects repeated rewarded actions
and avoided punishing actions, but this did not differ across stress. Reduced punishment,
but not reward, decay rates were seen under stress. Preliminary data from (N=9) anxious
individuals indicated that they were more likely to switch choices when stressed and also
show further reduced decay rates. These findings indicate that stress reduces the weight of
previous punishments on decisions which might, in turn, explain previous work
demonstrating increased punishment (but not reward) prediction error signal in the ventral
striatum under stress. Future work will explore the neurobiological mechanisms of these
effects and, critically, their contribution to pathological anxiety disorders.
63. MEGHAN ROSSI - UCL PSYCHOLOGY AND LANGUAGE SCIENCES
POSTER TITLE
Complex spatial processing in postsubicular head direction cells
AUTHORS
Rossi MJ, Lozano Y, Jeffery KJ
ABSTRACT
Head direction (HD) cells fire in relation to the animal’s directional heading and transmit this
information to several limbic structures, including the hippocampus. It has been shown that
HD cells integrate a variety of inputs, including from the vestibular and visual systems, to set
a preferred firing direction (PFD) while navigating a simple environment. The real world,
however, often contains more intricate arrangements of visual stimuli. To test our hypothesis
that HD cells are sensitive to complex spatial configurations of visual landmarks, we
recorded postsubicular HD cells as rats explored environments with 3 distinct cues
demonstrated to be salient in previous studies. Our preliminary results show that HD cells
largely lock to the cues as they rotate, indicating that the rat HD network is able to
distinguish between multiple distinct landmarks. Further experiments will examine if HD cells
are able to integrate changing configurations of landmarks, suggesting higher order spatial
processing (potentially using feedback from the hippocampus) and providing novel insight
into how our brains encode visual and spatial information in complex space.
64. AMAN SALEEM - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
Spatial decisions by the hippocampus in uncertain environments
AUTHORS
Saleem AB, Harris KD, Carandini M
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
ABSTRACT
Populations of place cells in the hippocampus represent the location of an animal in the
environment (O’Keefe & Dostrovski). One’s location in the environment is perceived on the
basis of sensory information. However, sensory information regarding the environment that
is available is often sparse, unreliable or noisy causing sensory uncertainty. How does
sensory uncertainty affect the hippocampal representation of location in an environment?
Increased uncertainty can be represented either by reducing the average firing rates of
neurons, as is seen in early sensory systems, or by increasing the spread of activity across
the population. Alternatively, the population of hippocampal neurons can follow attractor
dynamics, uncertainty might not change the representation of location in a snapshot of time,
but increase the variability of the responses across time. However, it is not know how the
representation by a population of place cells changes with uncertainty. Here we show that
increasing sensory uncertainty in the environment does not change the average firing rate of
neurons, or the spread of activity across the population. Instead, the responses of the
populations are more variable with higher uncertainty, causing more errors in the
representation of the environment. Further, animal’s behavioral errors were directly
correlated with the errors in the hippocampal representation.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Homeostatic and Neuroendocrine Systems | Elvin Hall
65. IDA BARLOW - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL BIOLOGY
POSTER TITLE
Understanding the role of a novel peptide implicated in zebrafish sleep
AUTHORS
Barlow I, Goel A, Zimmerman S, Schier A, Rihel J
ABSTRACT
Genetic and neuronal regulation of sleep is highly conserved from zebrafish to humans.
However, our understanding of the molecular and neurobiological mechanisms that regulate
sleep onset, length, and function remain relatively limited. Through a forward genetic screen
using a high-throughput locomotor tracking system of zebrafish larvae sleep, we have
identified a novel gene, dreammist (dmist), implicated in regulating vertebrate sleep.
Homozygous viral disruption to dmist decreases total sleep during the day and night, and
heat-shock overexpression at 5 days post-fertilisation (5dpf) increases sleep during the
night. Together, this data implicates Dmist as a putative sleep-promoting peptide.
Computationally predicted to encode a small transmembrane peptide, dmist gene structure,
synteny, and predicted peptide sequence is highly conserved among vertebrates.
Furthermore, in situ hybridisation and qRT-PCR show expression of dmist around the
zebrafish larvae brain ventricle from 1dpf. On-going experiments are investigating Dmist’s
subcellular localisation and detailed expression pattern, as well as exploring Dmist’s
similarity to the small transmembrane peptide and Na+/K+ ATPase pump regulator,
phospholemman. Therefore, investigations into Dmist’s function at the cellular and
behavioural level aim to provide a deeper understanding of Dmist’s role in regulating sleep
and wake, and possibly other biological processes.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Sensory and Motor Systems | Elvin Hall
66. NICOLAS BARASCUD - UCL EAR INSTITUTE
POSTER TITLE
Auditory pattern detection
AUTHORS
Barascud N, Friston KJ, Griffiths TD, Chait M
ABSTRACT
An important function of perception is to detect patterns in ongoing sensory input so as to
facilitate the prediction of future events. We used functional magnetic resonance imaging
(fMRI) and magnetoencephalography (MEG) to study the neural mechanisms underlying
listeners’ sensitivity to the emergence and violation of complex acoustic regularities
(characterized by repeating spectro-temporal patterns) in ongoing sound sequences.
Our stimuli were 50 ms tone-pip sequences containing transitions between random and
regularly repeating frequency patterns. In the MEG experiment (N=16), the stimulus set
consisted of four frequency patterns: REG – regularly repeating patterns of 10 tones (new
patterns were generated for each trial); RAND – a sequence of tones of random frequencies;
REG-RAND and RAND-REG sequences contained a transition between a REG and RAND
patterns (transition time was jittered across trials). In the fMRI experiment (N=16; different
subjects), participants were exposed to randomly alternating blocks of REG, RAND and
‘silence’ intervals. In both experiments, subjects were kept naïve and performed an
incidental visual decoy task.
MEG data show that brain responses to the emergence of regularity in RAND-REG signals
occurred from about 1.5 cycles, consistent with behavioural and modelling results, and
indicating that the brain rapidly detects regularities in ongoing input. Source analysis (based
on MEG as well as fMRI data) revealed a network consisting of auditory cortical sources
(primary auditory cortex bilaterally; extending in the left hemisphere along the superior bank
of the superior temporal gyrus; STG) and left inferior frontal gyrus (IFG), demonstrating an
interplay between early sensory processing and ‘higher level’ frontal mechanisms in the
course of regularity extraction, even in the absence of directed attention.
67. KHATEREH BORHANI - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Taking control of pain: the importance of selection agency
AUTHORS
Borhani K, Beck B, Khalighinejad N, Haggard P
ABSTRACT
Sense of agency (SoA) is the experience that our actions have consequences. It is unclear
whether SoA depends merely on recruiting the voluntary motor system (“motoric agency”), or
whether it rather requires that agents discriminatively choose between several different
actions, each producing a perceptibly different consequence (“selection agency”). We
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
examined how these two components of action control interact in a situation where actions
have important affective consequences, namely pain control. Participants made voluntary
actions that triggered laser heat-pain stimulation 250 ms later. They rated both pain intensity,
and perceived time of action or pain. Shifts between perceived timing of action and pain
provided implicit measures of SoA. We orthogonally varied whether the participant or the
experimenter chose between two keys causing higher or lower pain levels (selection
component), and whether the participant or the experimenter actually pressed the key
(motoric component). We found an interaction between these factors: actively pressing the
key produced stronger SoA, but only when the participant themselves selected pain level.
Further, selection agency significantly influenced pain perception. Action selection plays an
important role in pain control, by modulating both the experience of pain, and the experience
of control itself.
68. POSTER WITHDRAWN
69. SEAN CAVANAGH - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Differential modulation of two interneuron circuits in human motor cortex during action
preparation
AUTHORS
Cavanagh SE, Hannah R, Rothwell JC
ABSTRACT
Suppression of corticospinal excitability has been reported during movement preparation for
a choice reaction time (CRT) task, and may serve to prevent the premature release of
prepared responses and deselect inappropriate responses. We tested the idea that these
inhibitory processes reside in one or other of two different excitatory inputs to corticospinal
neurones (CSN-inputs).
To investigate this, we assessed the excitability of different CSN-inputs by recording motorevoked-potentials (MEPs), elicited by transcranial magnetic stimulation (TMS) over the M1hand area, at various stages during action preparation and selection of a CRT task.
Adjusting TMS pulse-width (30 and 120 µs) and direction of current induced in the brain
(posterior-anterior, PA; anterior-posterior, AP) allowed specific targeting of two separate
CSN-inputs: PA120-inputs and AP30-inputs.
AP30-pulses elicited MEPs with consistently greater onset latencies than those produced by
PA120-pulses; confirming selective recruitment of different CSN-inputs. During the CRT,
AP30-inputs were suppressed at the time of the imperative stimulus and in the non-selected
hand near to the onset of movement in the responding hand.
These results suggest a specific functional role of AP30-inputs in action preparation. Their
suppression implies they may be involved in co-ordinating the inhibition of premature
responses and in deselection of the non-selected hand.
70. FRANCESCO CONTI - UCL INSTITUTE OF CHILD HEALTH
POSTER TITLE
Control of transcription elongation is essential for cardiac and skeletal muscle development
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
AUTHORS
Bharj J, Usyaloglu M, Zheng D, Ross J, Osborn D, Jamshidi Y, Conti F
ABSTRACT
Background: Gene expression is often regulated at the level of transcriptional elongation,
when RNA polymerase II pauses along nascent mRNAs, effectively arresting gene
transcription. Its activity is resumed following the recruitment of transcription elongation
factors (TEFs). This level of regulation is widespread in particular among genes that are
developmentally regulated, but its role in the development of specific organs is not well
understood.
Aims and methods: To determine whether the control of transcriptional elongation plays a
role in development of cardiac and skeletal muscle in vivo, using zebrafish as a model
organism.
Results: We knocked down expression of a specific TEF using antisense morpholino
oligonucleotides in zebrafish. Morphants present with severe defects in cardiac
development, including oedema, looping defects and absent circulation. In skeletal muscle,
myofibres detach from the myosepta. These defects are similar to those observed in mutants
for dystrophin and integrins. Surprisingly, expression of these genes was maintained in TEF
morphants, suggesting that novel candidates may be involved. Global analysis of gene
expression via microarray and RT-PCR shows deregulated expression of numerous genes
involved in heart and skeletal muscle development.
Conclusions: The control of transcriptional elongation plays crucial roles in the development
of cardiac and skeletal muscle, and suggests that alterations in this process may underlie
cardiomyopathies and muscular dystrophy in patients.
71. ANDREW ERSKINE - NATIONAL INSTITUTE FOR MEDICAL RESEARCH
POSTER TITLE
AutonoMouse: a high-throughput, automated system for rapid behavioural training and
phenotype analysis in mice
AUTHORS
Erskine A, Bus T, Herb JT, Schaefer AT
ABSTRACT
A common bottleneck in neuroscience research is the laborious process of behavioural
training and testing to determine animal phenotype. We have addressed this by developing a
fully automated behavioural system (AutonoMouse) capable of training multiple mice
simultaneously on olfactory discrimination tasks without the need for water restriction.
We observed rapid acquisition of behavioural tasks in the system, with all tested groups
(n=6, n=14, n=9) reaching criterion (>80% in 100 trials) within 200 trials on all novel odour
tasks (out of 4) and within the first 100 trials on all odour recognition tasks (out of 3). Animals
consistently performed 100s of trials per day (mean, 40 days = 323 +/- 69 trials, n=29) and
readily initiated tasks, performing an average of 20 consecutive trials per session (20%
sessions > 37 trials, longest session = 271 trials). By utilising the system in a large scale
(n=50) olfactory bulb lesion study, we identified a range of olfactory phenotypes dependant
on the extent of lesion and task difficulty, cementing evidence for the role of the olfactory
bulb spatial map in odour identity coding. Overall, our results demonstrate that AutonoMouse
is a reliable phenotype analysis tool with significant potential for application to other stimulus
paradigms.
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72. PEDRO GONCALVES - GATSBY COMPUTATIONAL NEUROSCIENCE UNIT
POSTER TITLE
Optogenetic modulation of transient and sustained responses to tones in auditory cortex of
awake mice
AUTHORS
Goncalves PJ, Hildebrandt KJ, Sahani M, Linden JF
ABSTRACT
Many recent optogenetic experiments, involving brief and temporally precise manipulations
of activity in targeted classes of interneurons, have helped to unveil the instantaneous
impact of the targeted interneurons on cortical processing of sensory inputs. However, much
less is known about the roles of cortical interneurons in shaping the dynamics of cortical
spontaneous activity and its interaction with sensory input.
Here, we studied the involvement of parvalbumin-positive (PV+) interneurons in modulating
neural activity in the auditory cortex of awake mice. Continuous low-level activation of PV+
interneurons with stabilised step-function opsin (SSFO) produced a decrease in LFP power
in the high-gamma range during spontaneous activity and during sustained response to
tones. However, prolonged SSFO activation of PV+ interneurons increased transient LFP
responses to onsets and offsets of tones without substantially affecting overall tuning of
tone-evoked activity. These results are consistent with the hypothesis that auditory cortical
dynamics are shaped by synaptic depression: a decrease in spontaneous activity releases
intracortical synapses from depression, increasing transient cortical responses to sensory
inputs.
Overall, these results suggest that PV+ interneuron activity has a profound impact on
auditory cortical dynamics, modulating the relative strength of transient versus sustained
responses to sensory stimuli.
73. NIMA KHALIGHINEJAD - UCL INSTITUTE OF COGNITIVE NEUROSCIENCE
POSTER TITLE
Transferring experience of agency from voluntary to involuntary movement: a TMS study
AUTHORS
Khalighinejad N, Haggard P
ABSTRACT
Internal signals within the basal-ganglia-thalamocortical loops are associated with a
conscious sense of trying, or willing. Association between these signals with other events
could be a basic mechanism for acquiring sense of agency. We have investigated whether
healthy adults could acquire new agency-like experiences with respect to involuntary
movements, through such associative mechanisms.
Self-paced voluntary actions of one hand were paired with involuntary twitches of the other
hand, triggered by transcranial magnetic stimulation, followed by a tone 250ms later. These
learning trials alternated with test trials containing only involuntary twitches followed by
tones. Participants judged the time of the tone using a rotating clock display: a perceptual
shift of tone towards preceding action is an established index of agency. In a control
experiment, participants again judged the time of tone following an involuntary twitch, but the
twitch was never associated with any voluntary action.
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
Participants perceived tones as shifted towards the test trials with TMS-induced twitches that
caused them. This ‘intentional binding’ was absent in the control experiment.
We showed that coupling an involuntary movement to a voluntary action leads to acquiring
an agency like experience with respect to the involuntary movement. This research could
guide development of neuroprosthetic systems.
74. I-CHUN LIN - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
The nature of shared cortical variability
AUTHORS
Lin I-C, Okun M, Carandini M, Harris KD
ABSTRACT
Neuronal responses of visual cortex are highly variable, and this variability is correlated
across neurons. We asked whether this variability can be summarized by a few factors
affecting an entire neuronal population. We analyzed the activity of large simultaneously
recorded neuronal population in visual cortex. We developed a simple 'affine' model that
comprises two sources of shared variability: a multiplicative component that invests all
neurons in proportion to their instantaneous sensory drive and an additive component that is
independent of the sensory drive but affects individual neurons to different degrees. This
simple model captured the structure of trial-to-trial variability in the entire population and
predicted the complex relationship between correlation and individual neuronal tuning,
providing a simple and intuitive explanation for well-known phenomena observed at the level
of neuronal pairs, such as the stimulus-dependence of noise correlations.
Cross-validation analysis showed that the affine model performed better than either
multiplicative or additive models alone. The relative contributions of additive and
multiplicative fluctuations could vary over time and had marked impact on population coding.
This model reveals that shared cortical variability can be largely explained by two
components, multiplicative and additive fluctuations, that modulate the whole population.
75. POSTER WITHDRAWN
76. LEONIE OOSTWOUD WIJDENES - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
An investigation of resource limits in motor planning
AUTHORS
Oostwoud Wijdenes L, Ivry RB, Bays PM
ABSTRACT
Do movement plans, like representations of items in working memory, share their
resources? If this is the case, the precision of individual movements plans should decrease if
the number of movement plans increases. We examined if preparing one movement resulted
in less movement planning variability than preparing two movements by manipulating the
number of targets (Experiment 1) or the number of hands (Experiment 2). Participants made
speeded reaching movements towards visual targets. In a delayed response cueing
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
procedure, the number of planned movements was limited to a single target/hand, or
required planning of potential movements towards two targets/with two hands. For both
experiments, variability in initial movement direction was higher in the two-plan condition
than the one-plan condition, demonstrating a cost associated with planning multiple
movements, consistent with a limited resource. To test if the effect is due to an increase in
movement planning variability, or to a more general preparedness of the hand in the oneplan condition, we varied the timing of the target presentation in Experiment 3. The results
showed that initial movement variability was only decreased if the movement trajectory was
fully specified. We conclude that alternative movements cannot be planned independently,
even when they involve different limbs.
77. POSTER WITHDRAWN
78. JASPER POORT - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Learning enhances stimulus representations in primary visual cortex
AUTHORS
Poort J, Khan AG, Pachitariu M, Nemri A, Orsolic I, Krupic J, Bauza M, Sahani M, Keller GB,
Mrsic-Flogel TD, Hofer SB
ABSTRACT
How do cortical representations of sensory stimuli change as these stimuli become relevant
for behaviour? We studied this question in mouse primary visual cortex (V1) by using
repeated two-photon calcium imaging to follow the same layer 2/3 neurons across days.
Mice were trained to discriminate between two visual patterns presented on the walls of a
virtual corridor. Within a week, mice learned to selectively lick in response to one of the
gratings to obtain a reward.
Bilateral optogenetic silencing of V1 in PV-ChR2 mice showed that V1 was required for the
task. Increasing light intensity reduced performance in the visual discrimination task but not
in an odour discrimination task.
Day-to-day improvements in behavioural performance were associated with increasingly
distinguishable neural representations of task-relevant stimuli. This was the result of both an
increase in the stabilization of existing neurons and the recruitment of new neurons with
stimulus-selective responses.
These effects coincided with the emergence of different task-dependent signals during
learning: those that increased neuronal selectivity across the population when trained mice
engaged in the task, and those that reflected stimulus anticipation or behavioural choice
specifically in neurons that selectively responded to the rewarded stimulus.
79. FRED SCHWALLER - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
What the young brain tells the spinal cord: the changing developmental profile of top down
serotonergic modulation of dorsal horn sensory circuitry
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
AUTHORS
Schwaller F, Kanellopoulos A, Fitzgerald M
ABSTRACT
The development of postnatal sensory circuits is shaped by central modulation of sensory
inputs. In adults, serotonergic neurons in the rostroventral medial medulla (RVM) are an
important contributor to inhibitory and facilitatory descending modulation of dorsal horn
activity. Here we have investigated the contribution of this system to dominant descending
facilitation in young animals.
Mapping the postnatal maturation of 5-HT terminals in the lumbar dorsal horn using 5-HT
transporter immunoreactivity revealed a marked increase after postnatal day (P) 14. Ablation
of descending serotonergic neurons with intrathecal 5,7-DHT resulted in increased dorsal
horn neuron pinch-evoked firing activity at P40, but decreased brush and pinch-evoked firing
activity at P21.
Mapping 5-HT3 receptor expression in the dorsal horn revealed an adult-like distribution
from P7. Spinal administration of the 5-HT3 receptor antagonist ondansetron did not change
neuron activity in adults, but decreased brush and pinch-evoked firing at P21.
These findings show that when descending serotonergic terminals arrive in the lumbar spinal
dorsal horn, they strongly facilitate sensory input via dorsal horn 5-HT3 receptors. In
adulthood, the profile of descending serotonergic modulation changes. We suggest that this
is due to the late maturation of inhibitory interneuronal circuits, recruited via different classes
of spinal 5-HT receptors.
80. SAM SOLOMON - UCL PSYCHOLOGY AND LANGUAGE SCIENCES
POSTER TITLE
Spatial, temporal and contrast sensitivities of suppressive surrounds in mouse superior
colliculus
AUTHORS
de Franceschi G, Solomon SG
ABSTRACT
The classical receptive field (CRF) of neurons in the visual pathway is often embedded in a
modulatory ‘suppressive surround’, which may be useful in highlighting the important regions
of the visual image. We characterised suppressive surrounds of neurons in superior
colliculus, an area thought important in constructing salience. We made extracellular singleunit recordings from superficial layers of superior colliculus in 15 urethane anesthetized
mice. Response to drifting gratings was suppressed when the stimulus was enlarged beyond
the CRF in most (35/41) neurons, by on average 42% (SD 29). We then measured
responses to a small grating patch in the presence of annular gratings of varying contrast,
orientation, spatial or temporal frequency. Suppression was stronger at high contrast and
depended on contrast over patch and annulus. Suppression was generally tuned for spatialand temporal frequency and strongest near 4 Hz and 0.1 cycles/degree. Suppression was
less tuned for orientation, but in those neurons showing orientation tuning of suppression
(10/29), suppression was strongest for orientations like that over the CRF. We conclude that
a contrast gain control makes neurons in superior colliculus sensitive to spatial and temporal
context, which may be important in generating a map of salience to guide visual behaviour.
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81. CARSEN STRINGER - GATSBY COMPUTATIONAL NEUROSCIENCE UNIT
POSTER TITLE
Changes in inhibition explain cortical activity patterns and laminar variability
AUTHORS
Stringer C, Pachitariu M, Sosulski D, Ahilan S, Bartho P, Harris K, Latham P, Lesica N,
Sahani M
ABSTRACT
Activity in the brain varies greatly, from desynchronized firing to up-down states. Activity also
varies across layers, with superficial and deep layers exhibiting correlated variability while
granular layers show near-zero correlations. To understand these behaviors, we combined
computational methods with electrophysiological and anatomical studies. Our main result is
that inhibition both controls network states and produces diversity across layers.
We first analyzed multi-neuron stimulus-driven activity from the deep layers of auditory
cortex. We found that intrinsic large-scale fluctuations on multiple timescales can corrupt
sensory encoding in awake and anesthetized animals, but are abolished in desynchronized
states which encode stimuli with high-fidelity. We constructed a biologically-plausible spiking
network model with chaotic population-wide fast (50-200 ms) and slow (500-1000 ms)
fluctuations that quantitatively reproduced this behavior. Such chaotic network states are a
closer approximation to awake neural dynamics than the classical asynchronous state,
because in our data awake states displayed fast population-wide fluctuations. In simulations,
enhanced non-selective inhibition was essential to stabilize fluctuations and improve coding
properties. This is consistent with our data: putative fast-spiking inhibitory activity correlated
with increases in decoding accuracy and large decreases in tuning widths and noise
correlations.
Could laminar differences in noise correlations thus be due to inhibitory-stabilization? We
obtained laminar distributions of interneurons in auditory cortex from confocal imaging of PVconditional mouse lines and counted cells using a novel algorithm. The deep layers had the
lowest PV interneuron density while the granular layers had the highest. Incorporating this
distribution into our model we obtained zero noise correlations in the input layer but positive
correlations in the other layers. We further noticed that synchronized states can amplify
perturbations of single spikes, as recently observed. This work suggests that a thorough
understanding of inhibitory neurons, including subtypes, is critical for understanding the
behavior of networks in the brain.
82. MATTHEW TOPPING - UCL EAR INSTITUTE
POSTER TITLE
Mechanosensory pathways as potential targets for the control of insect-borne diseases
AUTHORS
Topping MP, Reuter M, Albert J
ABSTRACT
Mosquito-borne infectious diseases annually cause millions of deaths worldwide and
transmission of these diseases is inextricably linked to mosquito biology.
Our studies investigate the mechanosensory bases of various aspects of mosquito
behaviour. For example, it seems very likely that, in order to insert their proboscis into the
human skin, mosquitoes rely on sensory feedback from mechanosensory organs, such as
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
e.g. chordotonal organs. We test this by ablating chordotonal organ function using
chordotonal-specific insecticides.
Mechanosensory, and specifically chordotonal, signalling is also a crucial component of the
animals' air-borne courtship behaviour however. Using Drosophila melanogaster as a model
organism, we have tested the potential impact of ablating chordotonal organs on different
parts of the reproductive cycle.
Further, mosquito biting habits have a strong circadian component, with biting only occurring
during specific parts of the day. We examined the circadian rhythm activity patterns (in
response to light or temperature stimulation) of Drosophila with ablated chordotonal organ
function in order to explore any alterations in behaviour patterns.
Results and implications of these experiments will be analysed with new disease
transmission models, using the degree of mechanosensory impairment as a novel model
parameter.
We anticipate that our approach will lead to new vector control strategies.
83. BERNADETTE VAN WIJK - WELLCOME TRUST CENTRE FOR NEUROIMAGING
POSTER TITLE
Phase-amplitude coupling within the subthalamic nucleus correlates with severity of
Parkinson’s disease
AUTHORS
van Wijk BCM, Beudel M, Jha A, Oswal A, Foltynie T, Limousin P, Zrinzo L, Brown P, Litvak
V
ABSTRACT
Local field potential recordings from deep brain stimulation electrodes in the subthalamic
nucleus (STN) of Parkinson’s disease patients often show a distinct spectral peak around
300Hz. Recent studies have shown that the amplitude of these oscillations may be coupled
to the phase of beta band oscillations, and suggested a relation with clinical state. Here we
investigate this relationship in more detail by analyzing an extensive data set comprising 52
unilateral sites recorded from patients off dopaminergic medication (OFF), and 46 unilateral
sites recorded from patients on dopaminergic medication (ON). We correlated mean PAC
values and their frequencies in STN with contralateral hemibody akinesia UPDRS scores,
and found higher PAC values for patients with worse clinical symptoms, as well as a shift
towards lower phase frequencies. Although PAC showed a strong correlation with mean
beta band power, no strict 1:1 relationship between the peak frequencies was observed.
Significant PAC between high-frequency amplitude in the STN and beta band phase of
simultaneous MEG recordings was detected less often. This might be due to the different
frequencies at which PAC within the STN (low beta) and coherence between STN and motor
cortex (high beta) operate.
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Other Posters | Drama Studio
84. MARIAM ALEISSA - UCL DIVISION OF PSYCHIATRY
POSTER TITLE
Identifying genetic variants associated with Schizophrenia and Bipolar Disorder
AUTHORS
Aleissa M , Bass N, Curtis D, Fiorentino A, Sharp S, McQuillin A
ABSTRACT
Schizophrenia and Bipolar Disorder are common neuro-psychiatric diseases characterised
by chronic illness with highly heritable estimated to be as high as 80%. To understand the
molecular pathology of these disorders, it is important to unlock the nature of the molecular
pathogenicity. The aim of our study is to genotype promising potentially aetiological variants
in a well-defined cohort of individuals suffering from bipolar disorder or schizophrenia and in
a control cohort that has been selected for an absence of mental illness. Missense variants
that were predicted to lead to disruption of protein function were selected. Variants in the
following genes were selected for follow up: CLSTN3, GRM2, IFT74, IL6ST, ULK1, WARS,
MCPH1, SYT16, and DEFA4 genes. Interesting results were obtained for two rare variants,
in the MCPH1 gene. This study confirms previous findings, which suggests that there are
shared genetic susceptibilities for schizophrenia and bipolar disorder.
85. GIOVANNA ALFANO - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
New insights into the biological role of EYS, a major gene implicated in autosomal recessive
retinitis pigmentosa: from alternative splice variants to ciliary localisation
AUTHORS
Alfano G, Kruczek PM, Shah AZ, Jeffery G, Bhattacharya SS
ABSTRACT
EYS (eyes shut Drosophila homolog, MIM 612424) is one of the largest genes expressed in
the human retina. Mutations in EYS are the most common cause of autosomal recessive
retinitis pigmentosa (RP25 [MIM 602772]). EYS encodes a protein whose biological role is
presently unclear. This study was undertaken to investigate the role of EYS in the retina
aiming to gain insights into the pathogenesis of RP.
Immuno-localisation studies in Y79 cells have shown that EYS localises to the cell
membrane, primary cilium and the centrosomes. In monkey retina EYS localises to the
connecting cilium of rod and cone cells and to the cytoplasm of ganglion cells. Furthermore,
RT-PCR analysis revealed that previously uncharacterised EYS isoforms-2 and -3 are
expressed in the retina, testes and Y79 cells. Overexpression studies demonstrated that
both isoforms localise to the cytoplasm of cultured cells.
Our results suggest that EYS could play a multifunctional role in the primate retina, as it
shows a diverse localisation and may be a novel ciliary protein. Interestingly, the Drosophila
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
orthologue of EYS has been shown to participate in the organisation of Drosophila
photoreceptors. Investigating the role of EYS provides useful insights into the biology of
photoreceptors in health and disease.
86. SILKE BECKER - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
Modulation of Müller glia-derived neurotrophic factors by inflammatory cytokines during
hypoxia
AUTHORS
Becker S, Khaw PT, Limb GA
ABSTRACT
Retinal degenerative diseases are associated with hypoxia and inflammation. Müller glia
release neurotrophic factors, which mitigate retinal neuronal dysfunction and death. We have
investigated the production of neurotrophic factors by Müller glia in response to cytokines
and modulation of neurotrophin release by TGFβ during hypoxia. Müller glia expressed
mRNA coding for the neurotrophic factors BDNF, NGF, NT-3, CNTF, GDNF and NRTN, as
well as TGFβ1. TGFβ1 attenuated NGF and BDNF expression, while upregulating NT-3 and
GDNF mRNA. IL-6 decreased NGF expression and TNFα reduced NGF, BDNF, NT-3 and
GDNF mRNA. During hypoxia expression of TGFβ1, NGF and NT-3 were increased. While
BDNF mRNA expression was upregulated, protein release was not altered by hypoxia.
Inhibition of the TGFβ pathway by the SMAD3 inhibitor SIS3 and the Alk5 blocker SB43152
abolished hypoxia-induced upregulation of NT-3, but not NGF and BDNF expression. Müller
glia express a large number of neurotrophic factors, which are decreased by proinflammatory cytokines. Increased transcription of NT-3, but not NGF and BDNF, during
hypoxia was shown to be TGFβ1 dependent. Modulation of pro- and anti-inflammatory
factors in Müller glia may represent potential treatment targets in retinal degenerative
diseases to promote survival and function of retinal neurons.
87. TIFFANIE BENWAY - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Effect of the pentraxins in the CNS for drug target discovery
AUTHORS
Benway, TA, Edwards, FA, Yasvoina, MV, Foster, E, Richardson, JC, Salih, DA
ABSTRACT
Modulators of synaptic plasticity linked to Alzheimer’s disease pathology include the
pentraxin family members. The pentraxin most closely associated to the toxic effects of
amyloid-β is neuronal pentraxin (NPTX)1. It is known that NPTX1 forms complexes at the
synapse with the other similarly structured pentraxins NPTX2 and the receptor, NPTXR.
Here, we examine mRNA expression changes of NPTX1 with the other NPs at different ages
in two different mouse models of AD pathology: mice transgenic for human
APPswe+PSEN1M146V or Tau (MAPT). Localization of the NPs in the brains of these
models will be determined, and the effects of their overexpression.
Preliminary results support previous findings that NPTX1 colocalizes with amyloid plaques.
Current studies aim to further characterize the localization of other pentraxins in mouse
models of AD pathology, examine effects of overexpression of each NP to gain more
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information about the complexes that they form with one another. It is the intention of future
research to investigate the interaction of the pentraxins in disease progression, using mouse
models that feature the main pathologies of AD. From further characterization of these
proteins through disease, we aim to accomplish a greater understanding of the mechanism
of AD development.
88. SARAH BRIGHT - UCL INSTITUTE FOR WOMEN’S HEALTH
POSTER TITLE
Effect of curcumin on postnatal hypoxic-ischemic brain injury
AUTHORS
Bright S, Rocha-Ferreira E, Peebles D, Hristova M
ABSTRACT
Hypoxia-ischemia (HI) is a major cause of mortality and morbidity in children. It results in
brain damage associated with an inflammatory response and oxidative stress activating cell
death programs. The neonatal brain is particularly susceptible to HI damage because of
immature metabolizing enzymes and increased sensitivity to excitotoxicity and oxidative
stress, largely due to underdeveloped antioxidants and free radical scavengers, especially
damaging to mitochondria.
Therapeutic hypothermia is the only clinically approved treatment for HI but is only partially
effective. Therefore there is need for alternative treatments in HI.
Curcumin is an antioxidant, reactive oxygen species scavenger, anti-tumor, and antiinflammatory pleiotropic molecule. It attenuates mitochondrial dysfunction, stabilizes the cell
membrane and reduces the damage in adult models of spinal cord injury, cancer, and
cardiovascular disease. Nevertheless, no research has investigated the role of curcumin in
neonatal HI. Our aim was to investigate the effect of curcumin treatment in neonatal HI.
Post-treatment with curcumin following 60min HI in neonatal mice significantly reduced
microglial activation, TUNEL+ cell death, tissue loss and reactive astrogliosis compared to
vehicle-treated littermate controls.
Curcumin post-treatment reduced the histopathological damage markers post-HI, suggesting
neuroprotection. However, further research and long-term studies are necessary for fully
understanding curcumin’s impact in HI.
89. LORENZO CACIAGLI - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Memory encoding in patients with Juvenile Myoclonic Epilepsy and their unaffected siblings:
an fMRI study
AUTHORS
Caciagli L, Wandschneider B, Van Graan LA, Vollmar C, Centeno M, Thompson PJ,
O'Muircheartaigh J, Richardson MP, Duncan JS, Koepp MJ
ABSTRACT
Background: Juvenile Myoclonic Epilepsy (JME) is a frequent idiopathic generalised epilepsy
syndrome. Neuropsychology and fMRI studies report impaired frontal lobe functions and coactivation of the motor system during a working memory task both for JME and their
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unaffected siblings. The extent to which temporal lobe functions are also affected remains
controversial.
Aims: we aimed to characterize memory encoding networks and recognition performance in
JME patients and their unaffected siblings.
Methods: 31 JME patients, 12 siblings and 20 healthy controls underwent a memory
encoding fMRI paradigm in a 3T-MRI scanner, followed by an out-of-scanner recognition
task.
Results: recognition performances did not differ across the three groups. Compared with
controls, JME patients exhibited greater activations in the left sensory-motor cortex, bilateral
supplementary motor areas, superior temporal gyri and rolandic opercula across different
stimulus types. Comparable activation patterns were also observed in siblings.
Conclusion: we report fMRI evidence for hyperexcitability of the motor cortex during
cognitive tasks in JME patients and their siblings, suggestive of an imaging endophenotype
of JME. In the absence of between-group discrepancies in memory performance, we
interpret increased activations in the superior temporal gyri and rolandic opercula as a
compensatory mechanism for known frontal lobe disturbances in both groups.
90. JORGE IVAN CASTILLO-QUAN - UCL DEPARTMENT OF GENETICS, EVOLUTION &
ENVIRONMENT
POSTER TITLE
Aβ1-42 alters metabolism and stress response through age-related anorexia
AUTHORS
Castillo-Quan JI, Kinghorn KJ, Ivanov D, Cochemé H, Hardy J, Partridge L
ABSTRACT
Alzheimer’s disease (AD) is the most prevent form of dementia and neurodegeneration. The
greatest risk factor for AD is the ageing process. Indicators of health during ageing have
established that while mortality from cardiovascular and cerebrovascular disease is
decreasing, mortality secondary to AD is on the rise.
We previously showed that over-expression of Aβ1-42 in Drosophila adult neurons shortens
lifespan, accelerates age-related locomotor decline and induces neurophysiological defects
in the giant fibre system. Additionally we were able to show that older flies are more
susceptible to the toxic effects of Aβ1-42 as they die earlier than younger flies when
exposed to equivalent concentration of Aβ1-42 peptide.
To further understand the relationship of the ageing process and Aβ1-42 we have
characterised the response of flies expressing Aβ1-42 to different forms of stress at different
ages. The stressors tested include oxidative, xenobiotic and osmotic stress, and starvation.
We took advantage of the inducible GeneSwitch system to determine specifically when
these changes occur and their reversibility once Aβ1-42 is no longer expressed. We found
that older flies tend to be more susceptible to several forms of stress. However, we also
uncover that certain changes occur earlier than others, potentially pointing towards cellular
processes that are more susceptible to dysfunction in the presence of Aβ1-42. Additionally
we were able to characterise physiological and molecular changes that indicate an
organismal adaption to stress with concomitant adjustments in non-neuronal tissues. These
results suggest that expression of Aβ1-42 only in neurons also affects others systems.
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Our results hence provide a more comprehensive time line of defects happening after Aβ142 induction, potentially providing mechanistic insights as to the cascade of events leading
to neurodegeneration in Drosophila. Given the great evolutionary conservation of these
processes we consider likely that similar events occur in human suffering from AD.
91. ROSIE COLEMAN - UCL INSTITUTE OF CHILD HEALTH
POSTER TITLE
Language plasticity and function after surgery for focal epilepsy in children
AUTHORS
Coleman R, Croft L, Skirrow C, Harrison S, Cross JH, Rankin P, Sanfilippo P, Liegeois F,
Harkness W, Clayden J, Clark C, Vargha-Khadem F, Baldeweg T
ABSTRACT
Surgery for medication-resistant epilepsy often involves resection of tissue in close proximity
to eloquent cortex. The long-term effects of surgical resections on language ability are poorly
understood, especially in children.
We present preliminary findings from a follow-up study of 38 children who underwent
assessments for epilepsy surgery and 13 healthy sibling controls. Twenty-nine children had
surgery, and 9 children were deemed not suitable candidates for surgery. Mean elapsed
time from baseline to follow-up was 5 years. All patients with epilepsy underwent
neuropsychological assessments and language fMRI at baseline and follow-up. Language
fMRI using verb generation was used to determine language lateralisation in Broca's and
Wernicke's areas.
At follow-up, 69% of the surgical group was seizure-free compared to 0% in the non-surgical
group. In the surgical group, 90% showed stable or increased verbal IQ (VIQ) compared to
44% in the non-surgical group. Seizure-freedom and being free from medication was
associated with significant gains in verbal and performance IQ, and in processing speed.
Lateralisation of language function to the left temporal lobes at follow-up was associated with
gains in VIQ.
Our findings suggest better verbal intellectual outcome in those who had surgery and
became seizure-free, and those with typical temporal language lateralisation.
92. DANIEL COTFAS - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Investigating a novel single-gene neurodegenerative disorder with brain iron accumulation
using in vitro neuronal cultures derived from reprogrammed patient fibroblasts
AUTHORS
Cotfas A, Li M, Warner T
ABSTRACT
Introduction: A novel type of neurodegeneration titled "Beta propeller A protein associated
neurodegeneration" (BPAN) has been recently characterised in port-mortem brains. Patients
present with global neurodevelopmental delay, intellectual issues in childhood with
regression in early adulthood, progressive dystonic and parkinsonian symptoms and
dementia. MRI and post-mortem investigations elucidate some potential causes for these
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
symptoms; brain iron deposition in the substantia nigra and globus pallidus, and global tau
pathology. Our investigation focuses on the unexplored in vitro phenotype of affected cells.
Methods: BPAN-patients identified via clinical investigations, provide consent, and undergo
skin biopsy. BPAN-patient fibroblasts are cultured and expanded. Age- and gender-matched
controls are cultured in parallel. Pluripotency is induced via non-integrative episomal
nucleofection with plasmids to create iPS cell, which will be differentiated into the cells of
interest.
We aim to characterise the in vitro phenotype of cells that are most affected in BPAN. The
most likely candidates are: mesencephalic dopaminergic neurons (VMDA, A9 subtype of
SNpc), cortical neurons, and astroglia. We will investigate autophagy disorders, tau
pathology, iron deposition and axonal transport issues via ICC, western blot, RT-PCR,
qPCR.
93. SARAH CRISP - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Pathophysiology of glycine receptor antibodies
AUTHORS
Crisp SJ, Vincent A, Kullmann DK
ABSTRACT
Antibodies against glycine receptors (GlyRAbs) have been found in patients with acquired
neurological syndromes, which include oculomotor and autonomic disturbance, rigidity and
other evidence of disturbance of spinal inhibitory circuits. However, as with other neuropil
autoantibodies, the relationship between the identified antibody and neurological disease
remains conjectural. In some patients antibodies may be epiphenomena or present in low
titers of uncertain significance.
Using whole-cell patch-clamp we have recorded spontaneous miniature inhibitory
postsynaptic currents (mIPSCs) from motoneurons in rat dissociated spinal cord cultures.
GABA and glycine are co-released at interneuron-motoneuron synapses, both contributing to
mIPSCs. However, pharmacologically isolated glycinergic currents have a shorter decay
time than GABAergic currents. We use this difference in time course to separate the two
components, in the absence of pharmacological blockade, to quantify the contribution of
glycinergic neurotransmission to the mIPSCs recorded from motoneurons. We compared the
contribution of glycine to mIPSCs recorded from neurons incubated in patient IgG or control
IgG for up to 24h prior to recording.
Our preliminary results indicate that GlyRAbs from patients result in a reduction in
glycinergic neurotransmission. A reduction in glycinergic neurotransmission would be
consistent with many of the clinical phenotypes seen in patients with GlyRAbs.
94. SAM CUKA - UCL SCHOOL OF PHARMACY
POSTER TITLE
Novel Therapeutic Strategies in NBIA: A Gene Therapy Approach for PLA2G6-associated
Neurodegeneration (PLAN)
AUTHORS
Cuka S, Ng J, Hughes MP, Seino K, Waddington SN, Kurian MA, Rahim AA
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
ABSTRACT
Infantile neuroaxonal dystrophy (INAD) is a debilitating, intractable and ultimately lethal
neurodegenerative disorder. It is caused by mutations in the PLA2G6 gene that encodes for
phospholipase A. Patients present neurodegeneration-associated symptoms between six
months and three years of age. Severe spasticity, progressive cognitive decline, and visual
impairment typically result in death during the first decade. There is no disease-modifying
treatment available and palliative care focuses on quality of life. There is an overwhelming
need to develop novel therapies to treat INAD patients.
We aim to conduct a preclinical AAV-mediated gene therapy study to prevent
neurodegeneration and rescue a mouse model of INAD from premature death. We will use
recombinant adeno-associated virus serotype 9 vector (AAV9) to deliver therapeutic human
PLA2G6 gene to the neonatal INAD mouse CNS via either intracranial or intravenous
administration. The human PLA2G6 and control GFP gene were cloned into an AAV9
backbone plasmid, driven by the synapsin-I promoter and used to produce high titre viral
preparations. Furthermore, the INAD mouse model recapitulates many features of the
human phenotype. Investigating indices of neuropathology will not only provide us with
readouts against which to gauge therapeutic efficacy but also increase our understanding of
the underlying disease mechanisms.
95. DAMIAN CUMMINGS - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Hippocampal synaptic and genetic changes preceding a sharp increase in Abeta levels and
plaque deposition in a transgenic mouse
AUTHORS
Cummings DM, Portelius E, Bayram S, Yasvoina M, Benway TA, Ho S-H, Ali SS,
Richardson JC, Zetterberg H, Blennow K, Hardy JA, Salih DA, Edwards FA
ABSTRACT
At the time of clinical diagnosis, individuals carrying familial genes for Alzheimer’s disease
show substantial neuronal death and amyloid deposition. Understanding early phases of the
disease is therefore of utmost importance.
Early changes were studied in the hippocampus of transgenic mice carrying familial
Alzheimer’s disease genes (APP[Swedish]/PSEN1[M146V]). Abeta was detectable from 3
weeks but levels and Abeta42:Abeta40 ratios rose sharply between 2 and 4 months. At 4
months, the first amyloid plaques were detected but no discernible cell loss. From 2 months
there was an increase in the release probability of glutamate and a loss of spontaneous
action potential-dependent excitatory synaptic transmission. Long-term potentiation was
absent at 4 months. At this age, mice performed normally in hippocampal-dependent
cognitive tests (although increased levels of anxiety were indicated). At this early stage, the
groups of genes to show changes were enriched with synaptic genes and those related to
nerve impulses.
Synaptic and neuronal function is altered very early in these mice, prior to substantial rises in
Abeta and plaque deposition but in the absence of neurodegeneration. Identification of
genes involved in the synaptic changes may be useful in developing therapies to slow or
even prevent the progression of the disease towards neurodegeneration.
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96. PAUL DENNY - UCL INSTITUTE OF CARDIOVASCULAR SCIENCE
POSTER TITLE
Using Gene Ontology to characterise key participants in Parkinson's disease
AUTHORS
Denny P, Foulger RE, Martin M-J, Hardy J, Lovering RC
ABSTRACT
Gene Ontology (GO) is the established standard for functional annotation of gene products.
GO is used to summarise the function of a protein, the processes in which it is involved, and
its cellular location. Over 40,000 GO terms describe a wide range of biological concepts, and
are associated with gene products to create GO annotations. Yet there is an annotation
deficit for neurological proteins, which we are addressing with our Parkinson's UK-funded
GO project.
We are curating the literature to associate GO terms with Parkinson’s-disease relevant
proteins. We prioritise annotation targets based on (i) involvement in biological processes
related to PD, (ii) genes associated with PD risk, or (iii) protein interaction. In addition, with
input from neurobiologists we have begun to improve the Gene Ontology itself. These
expressive GO terms enable highly specific processes relevant to PD to be captured.
This effort is creating a unique public resource for the Parkinson's research community,
enabling researchers to rapidly evaluate and interpret existing high-throughput datasets and
guide future research. So far, we have annotated 260 papers, associated 3600 annotations
with 880 proteins and created 210 new GO terms. These annotations have led to
comprehensive annotation of synaptic vesicle transport, oxidative and ER stress responses
and mitophagy. Here we will present the improvement in annotations since the start of this
project in January 2014.
97. MICHAEL FLOWER - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Unsolved mysteries
AUTHORS
Flower MD, Shottlaender LV, Hanna MG, Houlden HH
ABSTRACT
I selected four hereditary conditions where the genetic cause is unknown in a large
proportion of cases.
Two are paroxysmal disorders; familial hemiplegic migraine (FHM), and episodic ataxia (EA).
In autosomal dominant cerebellar ataxias (ADCA) mutations in over 20 genes have so far
been implicated.
The genetic cause is unknown in 85% of FHM, 1/3 of EA, 50% of ADCA, and 2/3 of BVVL.
I collected DNA samples from 95 cases with paroxysmal disorders, 5 with ADCA and 7 with
BVVL, all of whom tested negative for known mutations.
Paroxysmal disorders show genetic and phenotypic heterogeneity. Novel mutations in genes
recently implicated in epilepsy, KCNC1 and STX1B, may therefore underlie unsolved FHM
and EA cases. I Sanger sequenced these genes in our samples.
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For ADCA and BVVL we applied a next-generation targeted exome panel to sequence
around 5000 known genes.
We identified heterozygous four novel heterozygous mutations in KCNC1 and 5 in STX1B.
In ADCA we identified 7 novel potentially disease-causing mutations, and 2 in BVVL.
Next we will model the functional implications of these mutations. Negative samples will be
analysed in more detail.
98. HEATHER GING - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
The specific neuronal vulnerability in Spinocerebellar Ataxia Type 1 (SCA1) is not associated
with CAG instability between different brain regions
AUTHORS
Ging H, Pigazzini ML, Pemble S, Sweeney MG, Nethisinghe S, Giunti P
ABSTRACT
Background: To date there are nine known polyglutamine (polyQ) diseases, which are fatal
neurodegenerative disorders, caused by a coding trinucleotide CAG expansion. This CAG
expansion is translated into an abnormally elongated glutamine tract in the respective
mutant proteins leading to protein aggregation and selective neuronal cell death.
Spinocerebellar Ataxia Type 1 (SCA1) is one of the polyQ disorders, which affects 1-3
people per 100,000. It is caused by a CAG expansion in exon 8 of the ATAXIN1 (ATXN1)
gene, which confers a gain of toxic function to the ATXN1 protein, resulting in defective
transcriptional regulation and RNA metabolism. The length of the CAG expansion inversely
correlates with the age at disease onset. Observations have shown that the interruption of
the CAG expansion by silent (CAA) or missense (CAT) mutations modulates the effect of the
expansion and delays the age at onset. We previously demonstrated (Menon et al., 2013)
that in a large cohort ataxia patients, 11% had histidine (CAT) interrupted pathogenic alleles
and that the age at onset inversely correlates with the longer uninterrupted CAG stretch. We
have the unique opportunity to study, for the first time, DNA extracted from the brain and
correlate it to the DNA extracted from the blood of two SCA1 patients. This allows us to
study the mosaicism in different tissues from the least affected to the most affected.
Objectives: This study aims to understand the somatic differences between human blood
and areas of the brain, of the same affected individual, variably involved in the
neurodegenerative process and their effect on the phenotype.
Method: Eight regions of the brain were chosen and the DNA extracted, fragment sized,
cloned and sequenced. The fragment sizing was performed using the 3730xl DNA analyser
machine. For cloning a 5.4kb plasmid pcDNA3.1(+) (Invitrogen) was used following
procedures described in Menon et al., 2013. The same method was used to analyse the
DNA previously extracted from the same patients lymphocytes.
Results: Firstly, fragment analysis showed that the cerebellum of a SCA1 affected patient
presented less somatic instability compared to other areas of the same brain. Secondly,
sequence analysis of clones established the base-by-base configuration of the CAG repeats
and found them to be largest in the caudate nucleus and shortest in the cerebellum, with
little variation throughout the other regions.
Conclusion: These findings argue against a direct association between instability and
specific neuronal vulnerability in SCA1, as the cerebellum is the most affected tissue in
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SCA1, and overall reveal that CAG instability throughout different tissues correlates poorly
with specific neuronal cell degradation, with no real difference between more affected and
less affected regions.
99. JOSE A GOMEZ-SANCHEZ - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL
BIOLOGY
POSTER TITLE
Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves
AUTHORS
Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo-Irigoyen M, Varela-Rey M,
Mirsky R, Woodhoo A, Jessen KR
ABSTRACT
Although Schwann cell myelin breakdown is a universal outcome of a remarkably wide range
of conditions that cause disease or injury to peripheral nerves, the cellular and molecular
mechanisms that make Schwann cell-mediated myelin digestion possible, have not been
established. We report that Schwann cells degrade myelin after injury by a novel form of
selective autophagy, myelinophagy. Autophagy is up-regulated by myelinating Schwann
cells after nerve injury, myelin debris is present in autophagosomes, and pharmacological
and genetic inhibition of autophagy impairs myelin clearance. Myelinophagy is positively
regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell
reprogramming in injured nerves. We also present evidence that myelinophagy is defective
in the injured CNS. These results reveal an important role for inductive autophagy during
Wallerian degeneration, and point to a potential mechanistic target for accelerating myelin
clearance and improving demyelinating disease.
100. SIMONE GRANNÒ - UCL SCHOOL OF PHARMACY / UCL INSTITUTE OF
NEUROLOGY
POSTER TITLE
Wnt signalling in Alzheimer’s disease and Down syndrome
AUTHORS
Grannò S, Berwick D, Plagnol V, Zanda M, Tybulewicz V, Wiseman F, Fisher E, Harvey K
ABSTRACT
Alzheimer’s disease (AD) is characterised by deposition of Aβ and tau protein aggregates,
cortical neuronal loss and impairment in memory and behaviour. Down syndrome (DS), the
most common human aneuploid disorder, is caused by trisomy of chromosome 21 (Hsa21).
The Wnt pathway is a highly conserved signalling cascade controlling the expression of
target genes with roles in cancer, stem cell differentiation and neurogenesis. In recent years,
aberrant Wnt signalling has been linked to development of AD. In DS, overexpression of the
Hsa21 gene dual specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) has
been implicated in the development of an early onset AD-like pathology. Here, we
investigate a potential relationship between Wnt signalling and Hsa21 trisomy. Our data
suggest a positive modulatory role of DYRK1A on canonical Wnt signalling activity in a
neuroblastoma cell line. Concurrently, ex vivo biochemical studies on the Tc1 mouse model
of DS suggest an overall imbalance in canonical Wnt signalling in the Tc1 brain, with an ADlike hippocampal profile. Overall, our data indicate that altered Wnt signalling may
significantly correlate with Hsa21 trisomy. The continuing study of its contribution to DS/AD
may provide further insight into the link between the two pathologies.
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101. ROSELLINA GUARASCIO - UCL INSTITUTE OF OPHTHALMOLOGY
POSTER TITLE
Expression and localization of NUB1 in Tauopathy and Alzheimer’s disease mouse models
AUTHORS
Guarascio R, Salih D, Edwards F, van der Spuy J
ABSTRACT
Alzheimer’s disease (AD) is characterized at a subcellular level by intracellular neurofibrillary
tangles (NFTs), aggregates of hyperphosphorylated Tau, and by senile plaques,
extracellular aggregates of amyloid beta peptides. Previous data revealed that Nedd8
ultimate buster 1 (NUB1) plays a role in reducing the aggregation and phosphorylation of
Tau in an in vitro model.
To clarify the role of NUB1 in AD, the spatiotemporal expression and localization of NUB1
was analyzed in T301L, a mouse model for Tauopathy characterized by NFTs, and in
TASTPM mice, characterized by early development of senile plaques.
The analysis revealed no change in the level of NUB1 expression in T301L mice and a
significant decrease at 12 months in TASTPM mice. In brain cryosections, NUB1 expression
was detected in the hippocampus and entorhinal cortex. Subcellularly, NUB1 was localized
predominantly in the neuronal nuclei, but also in neuronal processes. In both mouse models
at 12 months, NUB1 signal was observed to co-localize with AT8 positive cytoplasmic
aggregates. Moreover in TASTPM mice, a NUB1 cytoplasmic signal was observed in nonneuronal cells.
Our data confirm that NUB1 could be a therapeutic target in AD and also help to establish
the appropriate window of opportunity for therapeutic intervention.
102. SARAH HAMBURG - UCL DIVISION OF PSYCHIATRY
POSTER TITLE
Exploring EEG resting-state brain activity in young adults with Down syndrome: How alpha
band activity relates to cognitive abilities
AUTHORS
Hamburg S, Startin C, Strydom A
ABSTRACT
Brain activity in the alpha band is associated with IQ performance as well as specific
learning and memory processes in the general population. It has been suggested that
impaired cognitive abilities in individuals with Down syndrome (DS) may be related to
atypical alpha band activity (including power, frequency and topographical properties);
however conflicting results have been reported, particularly in relation to younger adults with
DS. We aimed to explore individual differences in alpha band properties (e.g. individual
alpha peak frequency) and their relationship with cognitive abilities in younger adults with DS
using resting-state electroencephalography (EEG), and will report cross-sectional data from
35 adults aged 16-35. Exploring alpha band properties may be important for understanding
brain development, brain maturation and cognitive decline in DS, as well as for identifying
potential EEG characteristics indicative of decline (biomarkers). Future work will involve
exploring the effect of ageing, cognitive decline, brain connectivity and network architecture
in adults with DS.
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103. JULIA HILL - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL BIOLOGY
POSTER TITLE
A novel inhibitor of the mitochondrial permeability transition pore is beneficial in an
experimental model of Multiple Sclerosis
AUTHORS
Hill JM, Pryce G, Baker D, Duchen M, Szabadkai G, Selwood D
ABSTRACT
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous
system, characterized by demyelinated lesions, which lead to neurodegeneration and
severely impaired motor skills. It was recently discovered that these lesions disrupt the blood
brain barrier, providing an opportunity for lesion specific drug targeting by compounds that
will not otherwise cross the blood brain barrier(Al-Izki et al., 2014). There is evidence for a
role of the mitochondrial permeability transition pore (mPTP) in the pathology (Forte et al.,
2007). mPTP is a large conductance pore that opens in the mitochondrial inner membrane,
causing loss of mitochondrial membrane potential and depletion of ATP, leading to a cellular
energetic crisis and cell death. Four novel compounds targeting the mPTP were developed
and screened in vitro using mitochondria isolated from mouse liver. Compounds were
screened in isolated mitochondrial preparations using the calcium retention capacity assay
to determine whether they inhibited mPTP opening. Compounds were compared to
cyclosporin A – the canonical inhibitor of pore opening. Two of the compounds inhibited pore
opening with significantly greater potency than CsA. The effects of the most potent
compound on mitochondrial function were investigated by respirometry and by
measurements of the mitochondrial membrane potential in cortical neurons. At low
concentrations, the compound did not alter respiration of isolated liver mitochondria or
neuronal mitochondrial membrane potential, although at high concentrations it reduced state
3 and maximal uncoupled respiration, and neuronal membrane potential. Importantly, in an
in vivo autoimmune encephalomyelitis mouse, a model of demyelinating disease, the
compound significantly improved clinical score and prevented deterioration of motor skills,
suggesting significant neuroprotective potential.
104. MICHAEL HUGHES - UCL SCHOOL OF PHARMACY
POSTER TITLE
Development of gene therapy for Niemann-Pick Type C disease
AUTHORS
Hughes MP, Tordo J, Massaro G, Ng J, Gissen P, Waddington SN, Platt FM, Rahim AA
ABSTRACT
Niemann-Pick type C is a lysosomal storage disorder, for which there is currently no major
disease modifying treatment. Loss of NPC1 function leads to systemic intracellular lipid
accumulation, however premature death is usually associated with neurological
manifestations, such as neurodegeneration and neuroinflammation. This project focuses on
the development of viral vectors capable of delivering and expressing NPC1 in the mouse
brain, via perinatal intracranial or intravenous injection, with the ultimate aim of ameliorating
brain and visceral pathology in the Npc1-/- mouse model.
To compare the different options available for gene delivery to the perinatal mouse brain a
vector study was carried out. Adeno-associated virus (AAV) vector produced the most
efficient and widespread gene delivery throughout the brain. However its limited packaging
capacity can be a constraint. To incorporate the relatively large NPC1 into a functional
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vector, extensive changes to the construct itself were made. This construct contains NPC1
under the control of the constitutively active neuronal promoter human synapsin 1 and was
used to produce AAV serotype 9, which combined have previously shown strong and
widespread expression throughout the mouse brain. We will use this vector as part of a
preclinical gene therapy study to rescue the Npc1-/- mouse model.
105. JULIAN JAEGER - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
A new FUS-Δ14 mouse model to dissect the pathobiology of FUS-ALS
AUTHORS
Jaeger J, Acevedo-Arozena A, Fisher EMC, Devoy A
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor neuron
system that leads to the progressive loss of motor neurons. The RNA-binding protein FUS is
one of several ALS causative genes, which highlights RNA processing as a potential key
mechanism in ALS. FUS is involved in RNA metabolism and shares structural and
functional similarities with another ALS-causing and RNA binding protein, TDP-43.
This study focusses on characterising the first available mutant FUS knock-in mouse model
of ALS (developed by Dr. Devoy) to examine the pathobiology of FUS-ALS. This model
expresses a splicing mutation that has been shown to cause early onset ALS in humans.
Characterisation includes the longitudinal investigation of motor function assessed by
behaviour tests and histological investigations with a focus on the spinal cord, cortex, and
neuromuscular junctions. Furthermore, molecular changes in the spinal cord and cortex will
be investigated by RNA sequencing in a longitudinal manner.
Our preliminary data point towards motor function impairments after 11 months of age and
impaired alternative splicing. Therefore, this novel model may provide a new resource in
FUS-ALS research for investigating the molecular mechanisms that cause this fatal disease.
106. KIRSI KINNUNEN - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Fronto-striato-thalamic tract structure is altered in familial Alzheimer’s disease and correlates
with cognitive function
AUTHORS
Kinnunen KM, Ridgway GR, Simpson I, Ryan, NS, Weston, P, Cash DM, Ourselin S, Fox
NC
ABSTRACT
Diffusion tensor imaging (DTI) assesses brain’s white matter tracts. Research is needed to
determine the behavioural relevance of DTI measures; this could improve tracking of
Alzheimer’s disease (AD). Familial AD (FAD) enables presymptomatic investigation. Tracts
interconnecting key brain regions could make networks vulnerable, leading to cognitive
impairment. We investigate three fronto-striato-thalamic circuits: anterior cingulate cortex,
dorsolateral prefrontal cortex and lateral PFC. Fifty-seven participants underwent 3T MRI, 33
with FAD and 24 healthy controls (HC). Based on Clinical Dementia Rating, 20 carriers were
presymptomatic (pMut+) and 13 symptomatic (sMut+) Thirty-seven participants were
neuropsychologically assessed (10 HC; 16 pMut; 11 sMut+). Tracts of interest were
delineated using probabilistic tractography in an independent HC group (n=20), and used to
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quantify the 57 participants’ fractional anisotropy (FA), mode of anisotropy (MO), tensor
norm (TN), and mean diffusivity (MD). Multivariate group differences in FA-MO-TN were
tested, followed by planned pairwise comparisons of FA and MD. Canonical correlation was
used to relate tract structure (FA-MO-TN) with neuropsychological function. Group
differences were found for multivariate FA-MO-TN in 9/12 tracts (p<0.05). Tract structure
within the circuits correlated with all cognitive domains (p<0.05). In conclusion, fronto-striatothalamic tract structure could provide a useful, cognitively correlated, DTI biomarker for FAD.
107. WENFEI LIU - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
The classification of microglial activation in the hippocampus of transgenic mice carrying
genes for dementia and the effects of Trem2 knockdown in microglia
AUTHORS
Liu W, Salih DA, Ali S, Cummings DM, Richardson JC, Edwards FA
ABSTRACT
Neuroinflammation is a well-known feature of Alzheimer’s disease (AD), and SNPs in
immune-related genes like TREM2 and CD33 are found to be risk factors for AD. This
suggests that microglia, the major immune cell type in the CNS, play an important role in the
disease. Here we characterise the microglial activation in the hippocampus of different
transgenic mouse models of dementia and knockdown Trem2 in microglia to investigate
Trem2 function.
Homozygous and heterozygous TASTPM mice carrying human APP695-Swedish mutation
and presenilin-1 M146V mutation were used as a model of amyloid-beta build-up in AD.
Heterozygous TauD35 mice with human tau P201L mutation were used as a model of tau
pathology. Serial sections were obtained. Microglia were stained with Iba1 and CD68
antibodies, and quantification in the hippocampus was performed using confocal
microscopy. BV-2 cells were transfected with Trem2 siRNA. Trem2 knockdown level and the
expression of microglial genes were assessed by qRT-PCR.
TASTPM mice show microglial activation closely associated with amyloid plaque deposition,
while in TauD35 mice microglial activation is detected with a considerable delay after
appearance of neurofibrillary tangles.
Carried out in accordance with Animals (Scientific Procedures) Act 1986 and GSK Policy on
the Care, Welfare and Treatment of Animals.
108. MARIA MAIARU - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL
BIOLOGY
POSTER TITLE
Improving chronic pain by targeting FKBP51
AUTHORS
Maiarù M, Tochiki KK, Cox MB, Géranton SM
ABSTRACT
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The comorbidity between chronic pain states and mood disorders such as depression and
anxiety remains poorly understood and the aim of this project was to explore the role of the
stress regulator FKBP51 in pain processing.
Differences in nociceptive behaviour were investigated in FKBP51 knock out (KO) mice and
in mice that received anti-FKBP51 siRNA intrathecally. Behaviour was observed in
inflammatory and neuropathic pain states. All procedures complied with the UK Animal Act
(1986).
The results obtained using KO animals and siRNA in WT mice demonstrated a strong
involvement of FKBP51 in nociceptive signaling. Specifically, KO animals showed a lower
sensitivity to mechanical stimuli both during and following the onset of long term
inflammation induced by CFA and neuropathic pain induced by SNI. Results obtained with
the siRNA delivered intrathecally indicated that spinal FKBP51 specifically plays a key role in
pain processing after injury.
Our findings therefore strongly suggest that spinal FKBP51 is involved in both the induction
and the maintenance phase of long-term pain states and is a good therapeutic target for the
treatment of chronic pain states.
109. ANDREEA MANOLE - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Riboflavin transporter neuronopathy
AUTHORS
Manole A, Jepson JEC , Pandraud A, Kullmann DM, Hanna MG, Reilly M, Houlden H
ABSTRACT
First described in 1894, Brown-Vialetto-Van Laere syndrome is a rare, autosomal recessive
neurodegenerative disorder characterised by bilateral sensorineural hearing loss, cranial
nerve palsies, respiratory insufficiency and severe sensorimotor neuropathy.
Our aims were to investigate: A) the scope of mutations occurring in these genes; B) the in
vitro effects of SLC52A2 mutations on cellular energy metabolism and mitochondrial function
in fibroblasts of patients; and C) the in vivo consequences of the loss of the SLC52A3
homologue in the fruit fly.
We used Sanger sequencing to screen 116 patients exhibiting cranial neuropathies and
sensorimotor neuropathy +/- respiratory insufficiency. We then performed functional assays
and measured activities of mitochondria respiratory complexes in patients with SLC52A2
mutations. We employed an RNAi-mediated gene knockdown of the Drosophila SLC52A3
homologue to recapitulate the loss-of-function phenotype of BVVL.
We identified 18 BVVL cases summing 5 SLC52A2 and 14 SLC52A3 pathogenic mutations.
Mitochondrial respiratory complex I and complex II activity were decreased in SLC52A2
mutation patients and carrier fibroblasts. Preliminary data will be presented regarding the
effect of a knockdown on aspects of mitochondrial function in Drosophila.
Overall our findings confirm the pathogenetic role of SLC52A2 and SLC52A3 in BVVL, and
thus have important clinical and therapeutic implications.
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110. AUDE MARZO - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL BIOLOGY
POSTER TITLE
Wnt signalling promotes full synapse recovery after synapse degeneration in the adult
hippocampus
AUTHORS
Marzo A, Galli S, Lopes D, Segovia-Roldan M, Podpolny M, Cacucci F, Gibb A, Salinas PC
ABSTRACT
Synapse degeneration occurs early in neurodegenerative diseases and strongly correlates
with cognitive decline in Alzheimer’s disease (AD). The molecular mechanisms triggering
synapse vulnerability and how synapse function can be restored after substantial synaptic
failure remain unclear. In AD, increased levels of the secreted Wnt antagonist Dickkopf-1
(Dkk1) contribute to Amyloid-β mediated synaptic failure. Using a transgenic mouse model
that inducibly expresses Dkk1, we demonstrate that Dkk1 expression in the adult
hippocampus triggers synapse loss, impairs long-term synaptic plasticity and induces deficits
in long-term memory. Importantly, cessation of Dkk1 expression induces a complete
restoration of synaptic function and long-term memory. We demonstrate that deficient Wnt
signalling compromises synaptic integrity in the adult brain resulting in hippocampal
dysfunction. Our results also reveal that Wnt signalling promotes a robust regeneration of
synapses and suggest that modulation of this pathway is a plausible therapy for functional
restoration at early stages of neurodegenerative diseases.
111. GIULIA MASSARO - UCL SCHOOL OF PHARMACY
POSTER TITLE
Intravenously administered gene therapy for the treatment of neuronopathic Gaucher
Disease
AUTHORS
Massaro G, Perocheau D, Karlsson S, Cheng SH, Waddington SN, Rahim AA
ABSTRACT
Gaucher Disease (GD) is an inherited metabolic disorder caused by mutations in the GBA
gene encoding the lysosomal enzyme glucocerebrosidase (GCase). Deficiency of GCase
produces an accumulation of glucosylceramide in macrophages within visceral organs and
brain. Neuronopathic forms of GD are characterized by neuronal loss, astrocytosis and
microglial proliferation. Enzyme replacement therapy is used to ameliorate the visceral
pathology, however there is no treatment available for the lethal neurodegeneration. Our
research focuses on type II GD, in which neurologic pathology results in death during early
infancy. The aim of this project is to intravenously administer an adeno-associated viral
vector serotype 9 (AAV9) carrying the functional GBA gene to a GCase-deficient murine
model of type II GD (K14-lnl/lnl) and assess the improvement in lifespan, brain and visceral
pathology.
AAV9 has been demonstrated to be able to cross the blood-brain barrier following
intravenous injection. We administered AAV9 carrying a therapeutic GBA gene into neonatal
K14-lnl/lnl mice which die 12 days after birth. Treated animals showed an increase in their
lifespan. The neurodegenerative pathology was ameliorated and some of the affected areas
of the brain were partially rescued. Histologic analysis of other organs and blood tests
revealed an improvement in the visceral pathology.
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112. CHRISTINA MURRAY - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Are there neuroprotective properties in the parvopyramidal layer of the presubiculum that
could prevent degeneration?
AUTHORS
Murray C, Gami P, Portelius E, Holton J, Zetterberg H, Revesz T, Lashley T
ABSTRACT
Background: Previous findings show that the parvopyramidal layer of the presubiculum
accumulates amyloidogenic proteins in a range of diseases, but only minimal neurofibrillary
degeneration is seen. However, in the neighbouring entorhinal cortex and subiculum severe
neuronal loss and deposition of amyloid plaques is observed.
Aims: Using post-mortem brain samples from AD cases, we aim to characterise the protein
deposits and determine the level of microglial activation in both the parvopyramidal layer of
the presubiculum and the neighbouring areas.
Methods: Immunohistochemistry was performed on cases of AD in order to visualise the
parvopyramidal layer of the presubiculum. Both the parvopyramidal layer and amyloid
plaques from the entorhinal cortex were laser captured for biochemical analysis of the
amyloid peptides. Microglial activation was also investigated.
Results: We observed a marked reduction in microglial activation and a decrease of Nterminally truncated and pyroglutamate modified Aβ peptides in the presubiculum compared
to the entorhinal cortex.
Conclusion: We have shown that in AD the parvopyramidal region contains diffuse deposits
of amyloidogenic proteins without neurofibrillary tangles or neuropil thread formation and
with minimal microglial activation. Understanding why may provide further insight into the
disease mechanisms.
113. MELANIA MUSCAS - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Therapeutic effects of modulation of the heat shock response in an animal model of Multiple
Sclerosis
AUTHORS
Muscas M, Pryce G, Al-Izki S, Baker D, Kalmar B, Greensmith L
ABSTRACT
Multiple Sclerosis (MS) is known to result in a significant lower motor neuron death. We have
previously shown that pharmacological upregulation of heat shock proteins (Hsps) with
Arimoclomol improves motor neuron survival and muscle function in mouse models of Motor
Neuron Disease. Here, we examined whether Arimoclomol could improve motor neuron
survival in the MS animal model, experimental autoimmune encephalitis (EAE).
Treatment with Arimoclomol increased motor neuron survival and improved muscle function
in EAE mice. Arimoclomol is known to upregulate the expression of Hsps by prolonging the
activation (phosphorylation) of heat shock transcription factor-1 (HSF-1). In untreated EAE
mice, there was a significant reduction in Hsp70 and HSF-1 expression in the spinal cord,
which was restored to normal by treatment with Arimoclomol. Furthermore, Arimoclomol
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increased the level of phosphorylated (activated) HSF-1. There was also a marked increase
in expression of inflammatory markers in the spinal cord of untreated EAE mice, but this was
only slightly reduced by Arimoclomol. Surprisingly, in EAE muscle there were no significant
disease-related changes in Hsp expression with or without Arimoclomol treatment. In
conclusion, Arimoclomol improves motor neuron survival and muscle function in a mouse
model of MS, by upregulation of Hsps in the CNS.
114. JOANNE NG - UCL INSTITUTE FOR WOMEN’S HEALTH
POSTER TITLE
Novel therapeutic approaches for childhood parkinsonism
AUTHORS
Ng J, Zhen J, Meyer E, Karda R, Baruteau J, Perocheau D, Buckley S, Massaro G, Hughes
M, Heales S, Pope S, Erreger K, Li Y, Borck G, Reith MEA, Rahim A, Waddington SN,
Kurian MA
ABSTRACT
Dopamine transporter deficiency syndrome (DTDS) is a primary neurotransmitter disorder
due to loss-of-function mutations in SLC6A3 encoding the Dopamine transporter (DAT). It is
clinically characterised by a progressive infantile-onset dystonia parkinsonism movement
disorder.
The aims of this study are to evaluate the clinical disease spectrum in DTDS, and to develop
a gene therapy approach using the DAT knockout mouse model.
We identified 8 new patients harbouring 5 novel missense mutations, and report a novel
atypical phenotype of juvenile parkinsonism. In vitro functional characterisation reveal that
disease mechanisms are multifactorial, including abnormal DAT trafficking, glycosylation,
impaired substrate recognition and uptake function.
We have established a DAT KO mouse colony, and demonstrated 42% survival rate at 5
weeks age, early hyperlocomotor features with parkinsonism, high HVA and degenerative
features with reactive astrocystosis. We have evaluated viral gene therapy approaches to
target the dopaminergic neurons in the neonatal mouse using Adeno associated virus (AAV)
modified by several promoters delivered by intracranial and intravenous delivery to P0 mice.
We are currently developing AAV9 viral gene therapy construct aiming to rescue the
phenotype of the neonatal DAT knockout mouse, with the long term goal of clinical
translation to DTDS patients.
115. TERESA NICCOLI - UCL DEPARTMENT OF GENETICS, EVOLUTION &
ENVIRONMENT
POSTER TITLE
Role of glucose metabolism in Alzheimer's disease
AUTHORS
Niccoli T, Cabechina M, Wong CT, Partridge L
ABSTRACT
Accumulation of A-ß42 peptide in the brain is thought to be the primary cause of Alzheimer's
disease pathogenesis. To study the effect of A-ß42 on the brain, we use a Drosophila
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2015 UCL NEUROSCIENCE SYMPOSIUM | POSTER ABSTRACT BOOKLET
melanogaster model of adult-onset A-ß pathology developed in the lab. We are analysing
the role of glucose metabolism in A-ß42 pathology using this model. Overexpression of the
Glucose Transporter, specifically in the neurons partially rescues the phenotype of A-ß42
expressing flies. We are analysing potential mechanisms mediating this effect.
116. NIAMH O'BRIEN - UCL DIVISION OF PSYCHIATRY
POSTER TITLE
Case only recurrent variation in CACNG4 is associated with Bipolar Disorder, Schizophrenia
and Alcohol Dependence Syndrome
AUTHORS
O'Brien NL, Lin Y, Fiorentino A, Way MJ, Sharp SI, Quadri G, Jarram A, Guerrini I, Smith I,
Thomson AD, Bass NJ, Morgan MY, Curtis D, McQuillin A
ABSTRACT
A case-case genome wide association analysis identified a variant, located 36kb from
CACNG5 and 79kb from CACNG4, to be associated, p<10−6 , with BD and SZ. CACNG4
and CACNG5 share 24% homology and are members of the γ subunits of the L-type voltage
gated calcium channel genes and function as transmembrane AMPA receptor regulators.
CACNG4 protein coding regions, promoter, 5’UTR and 3’UTR were screened for variants
which could increase an individual’s susceptibility to BD using high resolution melting curve
analysis (HRM).
HRM identified 21 SNPs in CACNG4. Two non-synonymous SNPs were chosen for follow
up genotyping in the BD, SZ ADS and control cohorts. Of these, rs371128228 was found in
each of the three case cohorts and absent in the control sample. The variant was found in 5
individuals with BD (p=0.061), 1 individual with SZ (p=0.14) and 3 individuals with ADS
(p=0.072). This SNP was not associated in the combined group p=0.078. Data from the
exome variant server (EVS) was used as an additional control cohort and rs371128228 was
only present in once in 4,229 samples. Using this data results in an overall association of p=
0.001 with the combined psychiatric phenotypes.
117. JOSHUA PAULIN - UCL DEPARTMENT OF NEUROSCIENCE, PHYSIOLOGY &
PHARMACOLOGY
POSTER TITLE
Overlaps in pathways regulating ageing and Alzheimer’s: changes in the insulin and insulinlike growth factor signalling pathway in mouse models of Alzheimer’s Disease
AUTHORS
Paulin J, Salih D, Edwards F
ABSTRACT
The Insulin and Insulin-like Growth Factor Signalling (IIS) cascade is an ancient and wellconserved pathway known to regulate lifespan, stress-resistance, and metabolism in many
organisms. With ageing potentially being a potent risk factor for developing Alzheimer’s
Disease (AD), elucidation of the importance of the pathways involved in the regulation of
ageing in the pathogenesis of AD have begun to take place. A pronounced increase in glial
Insulin-like Growth Factor 1 (IGF1) expression is seen in many neurological disorders,
including AD, suggesting it has a central role in the brain’s response to injury. The
implications of this endogenous increase on disease progression however have yet to be
determined. By defining changes in the signalling through the IIS pathway in the
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hippocampus of different AD model mice throughout the development of the disease, and
linking this to changes in glial IGF1 expression, I can begin to define the role of increased
IGF1 in AD, and determine whether any therapeutic benefit can be elicited from targeting
this process
118. POSTER WITHDRAWN
119. ALEXANDER PEPLER - UCL SCHOOL OF PHARMACY
POSTER TITLE
Identification of novel disease-causing variants in startle disease using exome sequencing
AUTHORS
Pepler A, Biskup S, Harvey R
ABSTRACT
Hyperekplexia or startle disease is a rare, early onset disorder characterised by exaggerated
startle in response to tactile stimuli. Currently, pathogenic variants in three genes have been
implicated in the hyperekplexia phenotype; Glycine receptor α1 (GlyR α1), glycine receptor β
subunit (GlyR β), and the glycine transporter (GlyT2).
Utilising the SureSelect5 exome capture kit, in conjunction with the SOLiD 5500xl NGS
platform, we generated approximately 120 million 72 base pair reads per sample, resulting in
approximately 100 million genome-aligned reads per sample. Variants were called where
mismatches to the reference genome (UCSC, Hg19) were identified.
The resulting raw variant lists contained approximately 200,000 single nucleotide variants
and insertions/deletions. Subsequent filtering and analyses were performed in order to reach
a shortlist of potentially causative variants within eight hyperekplexia trios.
We identified a case of allelic drop-out of the known GLRA1 Y279C pathogenic variant,
where identification by Sanger sequencing was previously unsuccessful. No clearly
pathogenic variants or shared genes were identified at this stage. Variants within ATRN and
UNC80 were highlighted due to involvement with the ‘zitter’ mouse (Kuramoto et al. 2001)
and the C. elegans ‘fainting’ phenotype (Yeh et al. 2008), respectively. Further work is
required to determine possible pathomechanisms.
120. ALEXANDRA PHILIASTIDES - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
The role of Fkbp family members in molecular mechanisms of prion propagation
AUTHORS
Philiastides A, Brown CA, Collinge J, Lloyd SE
ABSTRACT
Prion diseases are fatal neurodegenerative diseases. Genes other than the prion protein
gene can have an effect on susceptibility and phenotype.
Fkbp9 was identified as a potential prion modifier gene, following a microarray gene
expression study which correlated mRNA expression in uninfected brains, from 5 inbred
lines of mice, with their respective incubation times. An in-vitro bioassay, the scrapie cell
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assay (SCA) has validated the above findings, showing that Fkbp9 stably knocked down cell
lines exhibit a significant increase in prion propagation. The Fkbp9 protein is part of a family
of proteins known as immunophilins, which are peptidyl-propyl cis-trans isomerases. Fkbp
proteins have been implicated in neurodegenerative diseases, including Parkinson’s and
Alzheimer’s disease.
To establish whether other Fkbp proteins affect prion propagation, stable gene silenced
prion-susceptible neuroblastoma cell lines (N2aPK1/2) were generated for four genes
(Fkbp1a, 4, 5 and 8) using retroviral shRNA constructs. The genes encode Fkbp12, 51, 52
and 38 proteins respectively. The SCA was employed to test the effect of gene knockdown
on prion propagation, based on immunodetection of PrPres. Preliminary data suggests that
knockdown of Fkbp12 and 52 may reduce prion propagation. Understanding the role of Fkbp
family members in protein folding and aggregation may help to explain how these proteins
affect the pathology of neurodegenerative diseases.
121. JAMES PHILLIPS - UCL EASTMAN DENTAL INSTITUTE
POSTER TITLE
Engineered neural tissue made using CTX human neural stem cells for peripheral nerve
regeneration
AUTHORS
Day A, Murray-Dunning C, Phillips JB
ABSTRACT
Sheets of aligned engineered neural tissue (EngNT) can be made using a combination of
cellular self-alignment and stabilisation through the removal of some interstitial fluid. EngNT
can be used as an artificial endoneurium to support peripheral nerve regeneration, using
Schwann cells and more recently using stem cells that have been differentiated to resemble
Schwann cells. In order to progress this technology towards clinical translation, the use of
human neural stem cells as a potential allogeneic source of therapeutic cells is under
investigation, along with the development of optimised production processes.
The aim of this study was to investigate EngNT made with human neural stem cells as an
off-the-shelf therapy to treat peripheral nerve injury. Differentiated CTX human neural stem
cells were seeded within type I collagen gels, and cellular self-alignment followed by
stabilisation using RAFT™ (TAP Biosystems, UK) resulted in the formation of sheets of
EngNT. New equipment was developed and processes optimised to facilitate production at
scale. The phenotype of differentiated CTX cells was characterised in EngNT and the
aligned cellular material was assembled to form a guidance substrate and tested using a rat
model of peripheral nerve injury.
122. ELISAVET PREZA - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Stem cell models of C9orf72-linked Frontotemporal Dementia
AUTHORS
Preza E, Isaacs A, Rossor M, Hardy J, Wray S
ABSTRACT
The expanded GGGGCC repeat in an intronic region of C9orf72 is the most common genetic
cause of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. Recent studies show
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a role of expanded RNA and dipeptide aggregates as pathological features, supporting a
toxic gain of function disease mechanism while others show that loss of C9orf72 function
can also lead to disease. In our effort to understand the underlying disease biology, we are
studying cortical neurons from patient-derived induced pluripotent stem cells (iPSC). iPSC
were differentiated into cortical neurons using a dual SMAD inhibition protocol followed by an
extended period of in vitro neurogenesis. Cortical identity was confirmed by
immunofluorescence to both deep layer (Tbr1) and upper layer (Satb2) markers. To
generate a neuronal model for C9orf72 haploinsufficiency, we have generated CRISPR
constructs to disrupt we have targeted exon 2 of C9orf72 gene thus creating a functional
C9orf72 knock-out iPS cell line. The temporal expression and splicing of C9orf72 has been
investigated by analysis of C9orf72 protein and RNA levels throughout cortical development
in both control and patient-derived neurons. Studying these stem cell models will increase
our understanding on C9orf72 function as well as its role in Frontotemporal Dementia
pathogenesis.
123. LAURA PULFORD - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Mapping the genetic links between Down syndrome and Alzheimer’s disease
AUTHORS
Pulford LJ, Rickman M, Noy S, Tosh J, Abucewicz D, Tybulewicz, LJ, Fisher EMC, Wiseman
FK
ABSTRACT
Down syndrome (DS), caused by inheriting an extra copy of human chromosome 21
(Hsa21), leads to a greatly elevated risk of developing Alzheimer’s disease (AD). This is
largely due to triplication of the gene encoding the amyloid precursor protein (APP).
Evidence from mouse models has suggested that a gene or genes other than APP
exacerbates AD pathogenesis in DS. In order to narrow the region of Hsa21 contributing to
this deficit I have set up a novel cross between the Ts2Yey mouse model, trisomic for a
subset of ~40 Hsa21 orthologous genes on mouse chromosome 10 (Mmu10), with the J20
(APPSwInd) model of APP/Aβ pathology. Trisomy of this region rescues the sudden-death
phenotype observed in J20 mice, thought to be caused by epileptiform activity. A reduction
of astrogliosis is also observed in Ts2Yey trisomic mice, however no changes in the levels of
soluble or insoluble Aβ, Aβ plaque load or APP and relative levels of APP C-terminal
fragments have been observed. This highlights the complexity of AD pathogenesis in DS
and further studies are required to identify the genes and the mechanism responsible for this
unexpected neuroprotection.
124. SIRI RANLUND - UCL DIVISION OF PSYCHIATRY
POSTER TITLE
A polygenic risk score analysis of psychosis endophenotypes
AUTHORS
Ranlund S, Calafato S, Lin K, Arranz M, Bakker S, Collier D, Crespo-Facorro B, Diez A, di
Forti M, Giegling I, Hall J, Hall M-H, Iyegbe C, Jablensky A, Kahn R, Kalaydjieva L, Lewis C,
Mata I, McDonald C, McIntosh A, Murray R, Ophoff R, Picchioni M, PGC, Powell J, Rujescu
D, Shaikh M, Tosato S, Toulopoulou T, Van Os J, Walshe M, WTCCC, Bramon E
ABSTRACT
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Many single-nucleotide polymorphisms (SNPs) increasing risk of schizophrenia have now
been identified, and endophenotypes could help us to understand the phenotypic impact of
these risk loci. We tested whether polygenic risk score (PRS; the combined effect of a large
number of SNPs) for schizophrenia predicts brain structure/function and cognition, in a
sample of patients with psychosis, their unaffected relatives and healthy controls (total
N=3385). Endophenotypes included the P300 ERP (N=417), whole brain volume (N=684),
lateral ventricular volume (N=684), the Ray Auditory Learning task (N=1642), block design
(N=2380) and digit span (N=1404). PRS was calculated from the number of risk alleles an
individual carries for each SNP, weighted by the log(OR) provided by the Psychiatric
Genomics Consortium. PRS differed between groups (p<0.001); patients had the highest
scores, followed by relatives and last controls. Variance in endophenotypes accounted for by
PRS was low and mostly non-significant. 1% of variance in lateral ventricular volume, only at
the most liberal SNP inclusion threshold, was accounted for by the PRS (p=0.01).
SNPs associated with an increased risk of schizophrenia also influence lateral ventricular
volume. However, PRS did not influence other endophenotypes investigated. Lack of power
is a potential issue, with effects likely to be subtle.
125. SABINE REICHERT - UCL DEPARTMENT OF CELL AND DEVELOPMENTAL
BIOLOGY
POSTER TITLE
Assigning behavioural and brain developmental functions to genes of human
neurodevelopmental disorders
AUTHORS
Ghosh M, Reichert S, Hoffman E, Rihel J
ABSTRACT
Neurodevelopmental diseases such as autism and Prader-Willi are associated with a
number of behavioural abnormalities including disrupted sleep and epilepsy, which
negatively affect quality of life. Recent multi-genome comparison studies have identified
several genes that are likely to contribute to these disease phenotypes. However, the impact
of disrupted gene function on brain development and consequently behaviour remains
largely unknown, precluding mechanistic understanding and consequently targeted
pharmacological intervention.
To identify alterations in the development and function of sleep-regulating neurons and
circuits in these disorders, we are working to characterise zebrafish mutants in diseaseassociated genes, in terms of both their neuroanatomy and behaviour in conjunction with
targeted in vivo drug screening. The feasibility and potential of this approach is confirmed by
our recent work on the syndromic autism gene contactin associated protein-like 2. Our work
extends observations made in mouse models, including specific GABA-ergic deficits, seizure
liability, and sleep-wake phenotypes. Importantly, targeted drug screening based on cluster
analysis has identified a pharmacological suppressor of these zebrafish mutant’s sleep
phenotype. This demonstrates how our multidisciplinary approach allows us to
systematically associate mutations in autism risk genes with brain architecture, circuit
function, and behavioural phenotypes that in zebrafish can be screened for pharmacological
interventions.
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126. EMMA SCHUL - UCL SCHOOL OF PHARMACY
POSTER TITLE
Investigating the effect of exendin (EX-4) on hyposmia and the piriform cortex in a novel rat
model of early stage Parkinson’s disease (ESPD)
AUTHORS
Schul EV, Mercer A, Constanti A
ABSTRACT
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the
loss of dopamine (DA) in the substantia nigra (SN), underlying the presence of motor
symptoms, the presence of α-synuclein aggregates in Lewy Bodies (LBs), and
neuroinflammation. Its early stage is characterized by non-motor symptoms (NMS), including
hyposmia, and loss of brain noradrenaline (NA) preceding the loss of dopamine (DA).
Currently, a toxin model mimicking the early stage of PD (ESPD) is lacking and was
therefore designed. The GLP-1 receptor agonist exendin 4 (EX-4) is a potential novel
therapeutic candidate in PD treatment. Its effects were therefore studied in our novel ESPD
model.
Establishment of the novel rat ESPD model was carried out by confirming the presence of
hyposmia as a NMS, measuring the decrease in brain biosynthesis of DA and NA, and
identifying the presence of chronic neuroinflammation. The loss of NA was induced by a
single i.p. administration of N-2-chloroethyl-N-ethyl-2-bromobenzulamine (DSP-4), and DA
loss was induced by bilateral intrastriatal administration of 6-hydroxydopamine (6-OHDA) in
male Wistar rats. A study of different neuronal populations in the piriform cortex (a brain
region crucial for olfactory processing), in the ESPD model, revealed alterations in
parvalbumin-positive interneurones and rescue following EX-4 treatment.
127. SALLY SHARP - UCL DIVISION OF PSYCHIATRY
POSTER TITLE
Molecular Mechanism Underpinning Clozapine's Action
AUTHORS
Sharp SI, Weymer J, Gurling HMD, McQuillin A
ABSTRACT
We have identified genetic association between schizophrenia and genes involved in
clathrin-mediated endocytosis (CME). Many G-protein coupled receptors (GPCRs) have
affinity for antipsychotic drugs and CME is important for GPCR trafficking. The atypical
antipsychotic clozapine has greater efficacy and tolerability compared with typical
antipsychotics, likely explained by its strong serotonin (5-HT) receptor agonism and weak
dopamine receptor antagonism. There is evidence that clozapine increases clathrinmediated internalization of 5-HT receptors.
Our previous analysis of SH-SY5Y cells (RT-PCR) and mouse brains (microarray) has
demonstrated that clozapine, but not haloperidol, alters expression of CME-related and 5-HT
receptors genes. We have also shown that clozapine alters protein internalisation from the
cell membrane to recycling endosomes, suggesting a mechanism of action involving
intracellular signalling and altered GPCR recycling/degradation. Finally, we have identified
decreased expression of several pituitary hormones that may contribute to the side-effect
profile of clozapine, using RNA sequencing of brains from mice treated with clozapine for
four weeks.
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These findings will significantly advance our understanding of the therapeutic mechanisms of
action of clozapine and may identify novel, alternative treatment rationales, for people who
are clozapine-resistant and other patients groups with psychosis.
128. LUDMILA SHEYTANOVA - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Generation of a quantitative cell-based model for amyloid beta (Aβ) seeding and aggregation
AUTHORS
Sheytanova LM, Kloehn PC
ABSTRACT
Alzheimer’s disease (AD) is characterised by the pathologic accumulation of extracellular
amyloid β (Aβ) plaques and intracellular tau tangles. Aβ is released by sequential proteolysis
from the integral membrane protein amyloid precursor protein (APP). Despite compelling
evidence that Aβ aggregation can be seeded in APP-transgenic mice after intracerebral
inoculation of brain extracts from AD patients, but not from heathy controls, there are
currently no cell models to quantitatively assess the Aβ burden from patient samples. Such
cell models may not only be invaluable as biomarker tools, for screening small molecule
libraries, but also help to better characterise the underlying mechanism of Aβ aggregation
and toxicity in neurons. We have now sourced twelve commercial neuroblastoma cell lines to
study cell-dependent differences in seeded aggregation and toxicity after incubating soluble
fractions of AD and healthy control brain extracts. Whilst quantification of intracellular and
secreted Aβ alloform levels will help to identify the most favourable cell model, we will
investigate, in a systematic manner, how changes in the genetic makeup of cells affect the
sensitivity to seeded aggregation. This will include, but is not limited to enhancing
amyloidogenic processing by expression of mutant versions of APP and PS1 and genetic
ablation of proteolytic proteins.
129. KIMBERLEY SMITH - UCL SCHOOL OF PHARMACY
POSTER TITLE
Zebrafish dopamine transporter mutants: disease modelling and drug discovery in infantile
onset parkinsonism-dystonia
AUTHORS
Smith KM, Kurian MA, Harvey RJ
ABSTRACT
Dopamine transporter deficiency syndrome (DTDS) is caused by mutations in SLC6A3,
encoding the human dopamine transporter (hDAT). DTDS associated mutations result in
diminished dopamine/Na+ binding affinity, reduced cell-surface expression or a loss of posttranslational glycosylation, leading to loss of function of the dopamine transporter. Patients
classically present with infantile-onset progressive parkinsonism-dystonia. As the disease
progresses, patients develop hypokinesia with parkinsonian features, and in the absence of
disease modifying therapies, many DTDS patients die in adolescence. The aim of this study
was to generate a stable zebrafish DAT mutant in order to a) model DTDS in an invertebrate
model system; and b) to establish a high-throughput assay to identify possible novel
therapeutic molecules for treating this devastating disorder. Originally utilized by bacteria to
mediate defense against viruses and other foreign nucleic acid, CRISPR/Cas9 systems can
be engineered to cleave double stranded DNA in vitro, specific to regions of interest.
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CRISPR/cas9 genome editing technology, along with next generation sequencing, has been
employed to generate a stable DAT zebrafish mutant. In addition, the expected phenotype of
the mutant fish has been investigated with morpholino gene knock-down of SLC6A3 and
pharmacological inhibition of DAT. Preliminary data suggests loss of DAT function lead to a
marked reduction in zebrafish swimming behaviour.
130. CHARLOTTE SPICER - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Investigating the effects of pharmacological up-regulation of the heat shock response in a
transgenic mouse model of inclusion body myopathy
AUTHORS
Spicer C, Ahmed M, Hanna MG, Greensmith L
ABSTRACT
Sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease
affecting adults over 50-years-old. Although the precise cause of sIBM remains unknown, it
is characterised by both inflammatory and degenerative features. However, trials of antiinflammatory agents have all been unsuccessful and to date there is no effective diseasemodifying treatment for IBM.
Protein mishandling in cells leads to accumulation and aggregation of proteins, characteristic
of IBM pathology. We have previously demonstrated that co-induction of the cytoprotective
heat shock response by treatment with Arimoclomol, ameliorates IBM-like pathology in
cultured muscle cells by improving protein handling.
We investigated the effects of Arimoclomol in vivo by treating transgenic mice with a
mutation in the valosin-containing protein (VCP) gene. This mouse models multisystem
proteinopathy (MSP) and recapitulates many of the key features of sIBM in muscle. We
examined the muscle of mutant VCP (mVCP) mice to assess the therapeutic effects of a
pre-clinical trial of Arimoclomol.
Histological examination showed evidence of key IBM-like characteristics in the muscle of
mVCP mice, including TDP-43 mislocalisation, ubiquitin-positive inclusions and increased
centralised nuclei. Arimoclomol treatment significantly attenuated all of these pathogenic
features in muscle.
These in vivo findings confirm our in vitro data and suggest that Arimoclomol may be a
potential therapeutic agent for the treatment of sIBM.
131. VASILEIOS TENTOLOURIS-PIPERAS - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Brain network morphometry and structural connectivity underlying
visuospatial/visuoperceptual impairments in PCA
AUTHORS
Tentolouris-Piperas V, Kinnunen K, Shakespeare T
ABSTRACT
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Background: Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome with
atrophy of the parietal and occipital lobes, and deficits in visuoperceptual and visuospatial
processing. It is most commonly caused by Alzheimer’s disease (AD).
Aims: To investigate the relationship between performance on visuospatial/visuoperceptual
tasks, particularly the usual/unusual views test, and structural abnormalities of brain
networks supporting these functions in PCA patients compared to typical AD and normal
controls. To examine how findings will relate to existing hypotheses on visual processing
organisation and visual object identification.
Methods: Participants were identified from the DRC PCA cohort: 43 PCA, 29 typical AD
patients, and 37 controls. A VBM analysis was carried out on T1-weighted images, followed
by a diffusion data analysis using probabilistic tractography. Multivariate statistical analysis
was carried out for potential correlations between neuropsychological and imaging findings.
Results: PCA patients are expected to show loss of volume in key regions of the visual
system and occipital cortex networks, and to show altered structure of these networks’ white
matter connections.
Conclusion: Diffusion tractography findings could relate to specific cognitive impairments
characteristic to PCA patients. A correlation with neuropsychological data could provide
evidence to further elucidate the organisation of visual processing and identification
networks.
132. EMMA WILSON - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Cellular pathomechanisms of Hereditary Sensory and Autonomic Neuropathy type 1 (HSAN1) in primary motor neurons
AUTHORS
Wilson E, Kalmar B, Kugathasan M, Reilly MM, Greensmith L
ABSTRACT
HSAN-1 is a peripheral neuropathy related to Charcot-Marie-Tooth disease, caused by
missense mutations in the SPTLC1 / SPTLC2 genes. These genes code for two subunits of
the enzyme serine palmitoyltransferase (SPT) which catalyzes the first and rate-limiting step
of de novo sphingolipid synthesis. It has been proposed that mutations in SPT cause a
change in enzyme substrate specificity, which results in the production of atypical
sphinganines, deoxysphinganine (DSp) and deoxymethylsphinganine (DMSp), rather than
the normal enzyme product, sphinganine (Sp). Accumulation of DSp and DMSp have been
proposed to cause the neurodegeneration observed in HSAN-1 patients.
The aim of this study was to characterize DSp and DMSp-mediated neurotoxicity in primary
mouse motor neurons and to investigate the potential mechanisms that may underlie DSp/
DMSp neurotoxicity. Specifically, we examined mitochondrial function and changes in
intracellular calcium, which have been shown to be altered in other sensory and motor
neuron disorders.
Our results show that the abnormal enzyme products DSp and DMSp have a dosedependent, neurotoxic effect in primary motor neurons. These abnormal sphingolipids not
only result in a reduction in neurite outgrowth but also induce significant cell death. In
addition, motor neurons treated with sphinganines display mitochondrial abnormalities as
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well as abnormal intracellular calcium levels, suggesting that the toxic effects of DSp and
DMSp may be mediated by these deficits.
133. KATE WOLFE - UCL DIVISION OF PSYCHIATRY
POSTER TITLE
Predictors of pathogenic copy number variation in adults with idiopathic intellectual disability
and co-morbid neuropsychiatric disorders
AUTHORS
Wolfe K, McQuillin A, Strydom A, Bass N
ABSTRACT
Chromosomal copy number variants (CNVs) are increasingly implicated in the aetiology of
neurodevelopmental and neuropsychiatric disorders. Multiple congenital abnormalities
(MCA) and autistic spectrum disorders (ASD) have been found to be indicative of underlying
CNV pathology in paediatric populations with intellectual disabilities (ID). Adults with ID and
co-morbid neuropsychiatric disorders remain largely untested and there is a lack of
knowledge of clinical predictors of CNV pathology in this cohort.
250 adults with ID and co-morbid psychiatric disorders were recruited through UK ID
psychiatry services and array CGH was undertaken using the Nimblegen 135K platform.
Clinical predictors of interest include: gender; degree of ID; family history; co-morbid physical
and mental health problems; behavioural presentation and forensic in-patient status. A
preliminary univariate analysis using SPSS was undertaken to analyse the role of these
variables as predictors of CNV pathogenicity.
MCA or ASD were not found to be significant predictors of CNV pathogenicity. Forensic inpatient status was the only significant predictor of CNV pathogenicity. Future research with a
forensic in-patient cohort would need to comprise comprehensive behavioural phenotyping
and forensic history taking as a starting point for analysing the likely complex interplay
between genetic risk factors, the environment and criminal behaviour.
134. SHI-YU YANG - UCL INSTITUTE OF NEUROLOGY
POSTER TITLE
Using neural crest stem cell-derived dopaminergic neurons to mimic pathogenesis of GBA1associated Parkinson’s disease
AUTHORS
Yang SY, Beavan M, Schapira AHV
ABSTRACT
Parkinson’s disease (PD) is the second commonest neurodegenerative disease affecting
approximately 4% of people >80 years. Important progress in understanding PD
pathogenesis has been based on human post-mortem samples, chemically-lesioned
animals, transgenic animals and in vitro models; however these models all have limitations.
We developed a novel human neuronal cell model from heterozygous GBA mutation positive
subjects, in which we isolated neural crest stem cells from GBA heterozygous mutated
subjects’ adipose tissues. The isolated neural crest stem cells were differentiated to
functional dopaminergic neurons with higher efficiency. This model has successfully
mimicked specific biochemical features of GBA1-associated PD and offered us a unique
opportunity to examine cell-type specific pathology in the vulnerable dopaminergic neurons
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derived from PD patients. These cells provide a suitable platform for drug screening for
drugs that may target selected pathways in PD pathogenesis.
135. AURA ZELCO - UCL SCHOOL OF PHARMACY
POSTER TITLE
An assessment of neuroprotective/regenerative properties of exendin-4 following hypoxicischemic insult to the brain
AUTHORS
Zelco A, Rocha FE, Rahim AA
ABSTRACT
Background: The study investigated if Exendin-4, an analogue of Glucagon-Like Peptide 1,
has neuroprotective and/or neuroregenerative effects in a mouse model of hypoxicischaemic brain injury.
Methods: At postnatal day 7, animals underwent unilateral carotid occlusion followed by 30
minutes 8% oxygen exposure. Neuroprotection group received one dose (5µl/g) of either
Exendin-4 or saline and were transcardially perfused 48 hours later; neuroregeneration
group received additional lower doses of either Exendin-4 or saline every 12 hours for 14
days and daily tested using grid walk assessment. Brains of both groups were histologically
assessed for tissue infarction and cell death, but neuroprotection group was also assessed
for astroglia activation.
Results: Exendin-4 administration resulted in significant neuroprotection 48 hours after HI;
there was reduction in cell death (p=0.046), activated astroglia (p=0.04) and tissue loss
(p=0.056), especially in the hippocampus, striatum and thalamus.
In the neuroregeneration study, Exendin-4 treated mice performed better on grid walk test,
but there was no effect in the histological assessments.
Conclusions: Exendin-4 after 48 hours showed a neuroprotective effect that was lost in the
longer treatment; a delaying in the injury rather than an actual neuroprotection could cause
this difference, even if Exendin-4 improves motor function.
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Other Posters | Drama Studio
136. PETER ATKINSON - EISAI
POSTER TITLE
A collaboration in drug discovery for neurodegeneration
AUTHORS
Eisai:UCL Therapeutic Innovation Group
ABSTRACT
In December 2012 Eisai Co., Ltd. and University College London (UCL) announced a
pioneering collaboration to identify and validate novel drug targets and develop new
therapeutics for the treatment of neurological diseases such as Alzheimer’s, Parkinson’s and
other related disorders. Since establishing the collaboration we have initiated four TIG
projects which are currently undergoing Target Validation in key areas of interest for
potential CNS disease intervention including mitochondrial dysfunction, protein aggregation
and misfolding and neuroinflammation. The collaboration brings UCL scientists together with
Eisai’s drug discovery research team (based in Hatfield, UK), wider drug development
expertise from across the organisation and access to a focussed compound library for
screening. We have also hired a number of TIG scientists to work within PI labs at UCL to
enable further development and translation of the science around a target. As our existing
projects mature we now welcome new proposals from UCL researchers, to include additional
areas of interest such as endoplasmic reticulum stress, axonal transport and neurovascular
dysfunction. For further information please contact David Miller (david.d.miller@ucl.ac.uk)
and Andy Takle (Andy_Takle@eisai.net)
137. ALVARO DIEZ - UCL DIVISION OF PSYCHIATRY
POSTER TITLE
Dynamic causal modelling of the spatial network related to the P300 evocation in healthy
and psychotic population
AUTHORS
Díez Á, Ranlund S, Adams R, Walshe M, Murray R, Friston K, Pinotsis D, Bramon E
ABSTRACT
DCM is a Bayesian model inversion method developed to estimate how event-related
responses result from the dynamics of coupled neural populations and how these are
influenced by experimental changes. We used DCM to obtain an optimal spatial model
related to the P300 response in healthy and psychotic population. 24 patients with
psychosis, 24 unaffected relatives and 25 controls underwent EEG recording during an
auditory oddball paradigm. We a priori selected several plausible spatial models for the
P300; including temporal, parietal and frontal regions. Using DCM we then analysed and
selected the best model for explaining the differences between task conditions. The best
explanatory model in healthy participants included Primary Auditory Cortices (A1), Superior
Parietal Lobules (SPL) and Superior Frontal Gyri (SFG). The addition of Superior Temporal
Gyri (STG) did not improve the outcome. The winning model in patients included only A1
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and SPL. Superior rather than inferior parietal and frontal structures were more decisively
involved in the healthy P300. However, SFG was not essential in patients, which is in line
with frontal hypoactivity and reduced P300 amplitude in psychosis. We obtained an optimal
brain spatial model for further P300 effective connectivity studies involving both healthy and
clinical population.
138. POSTER WITHDRAWN
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UCL Neuroscience Domain
Thanks to all of our sponsors
UCL Faculty of Brain Sciences
UCL Hospitals Biomedical Research Centre
UCL Division of Biosciences
Gatsby Computational Neuroscience Unit
UCL Division of Psychology and Language Science
UCL School of Pharmacy
UCL Division of Psychiatry
UCL Faculty of Medical Sciences
UCL Institute of Ophthalmology
UCL Translational Research Office
UCL Ear Institute
UCL Institute of Neurology
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