The Saskatchewan Neuroscience Network Research Day/Altschul Mini-Symposium June 21 and 22,
2012
Below is the schedule for the two-day neuroscience research event to be held at the Graduate Student
Commons on June 21 and 22, 2012. The first day involves a mini-symposium “Long-term effects of
early developmental challenge on brain and behaviour” with five invited speakers giving
presentations. The second day is a broad neuroscience research day with presentations from PI’s in
Saskatchewan in the morning, a student poster session, and two keynote addresses in the afternoon.
The main goals of the event are: 1) to promote the exchange of ideas related to brain research among
individuals from Saskatchewan and abroad; and 2) celebrate the large and active neuroscience
research community in Saskatchewan.
Sessions will be held at the Graduate Student Commons (1337 College Drive, U of S campus). All are
welcome. Please RSVP Dr. John Howland (Physiology, U of S) at john.howland@usask.ca if you plan
on attending.
The event and meals are free due to the generous support of the Altschul Symposium Fund,
Saskatchewan Health Research Foundation, College of Arts and Science, the University of
Saskatchewan Conference Fund, and the University of Saskatchewan Vice-President Research Office.
Altschul Mini-Symposium “Long-term effects of early developmental challenge on brain and
behaviour”
Schedule – June 21, 2012 (Note: abstracts follow the schedule)
12:30 Lunch and introductions
1:00 Ina Weiner, PhD, Department of Psychology, Tel-Aviv University, Tel-Aviv, Israel
“Tracing the development of psychosis and its prevention in an animal model.”
1:45 James I. Koenig, PhD, Maryland Psychiatric Research Center, Department of Psychiatry, University
of Maryland School of Medicine, Baltimore, MD, USA
“Fetal stress exposure elicits enduring changes on the adult brain and behavior: implications
for schizophrenia.”
2:30 John G. Howland, PhD, Department of Physiology, University of Saskatchewan, Saskatoon, SK
“Antagonism of ELR-CXC chemokine receptors during pregnancy prevents the long-term
cognitive changes caused by maternal immune activation in rats.”
3:15 Break
3:30 Aaron J. Gruber, PhD, Lethbridge Brain Dynamics Group, Department of Neuroscience, University
of Lethbridge, Lethbridge, AB
“Brain insults early in life alter cortical activity and impair economic decision-making in rats.”
4:15 Sylvain Williams, PhD, Department of Psychiatry, Douglas Institute and McGill University,
Montreal, QC
“Investigating early anatomical and functional changes in the hippocampal GABAergic network
in a prenatal infection model.”
5:00 General Discussion
7:00 Dinner (by invitation only)
Saskatchewan Neuroscience Network Research Day
Schedule – June 22, 2012 (Note: abstracts follow the schedule)
9:00 Opening Remarks
9:15 Lisa E. Kalynchuk, PhD, Canada Research Chair, Department of Psychology, University of
Saskatchewan, Saskatoon, SK
“Reelin and the pathogenesis of major depression.”
9:45 Josef Buttigieg, PhD, Department of Biology, University of Regina, Regina, SK
“Hypoxia and hypercapnia sensing by pulmonary neuroendocrine cells.”
10:15 Jack R. Gray, PhD, Department of Biology, University of Saskatchewan, Saskatoon, SK
“Neural control of adaptive behaviour: Good things come in small packages.”
10:45 Break
11:00 Ron Borowsky, PhD, Department of Psychology, University of Saskatchewan, Saskatoon, SK
“Strategic effects of instructions on the ventral-lexical reading stream:
converging evidence from neuroimaging and reaction time.”
11:30 Darrell D. Mousseau, PhD, Saskatchewan Research Chair in Alzheimer’s Disease and Related
Dementias, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK
“What is the intersection between depression and dementia?”
12:00 Lunch and Student Poster Session
2:00 Michael E. Kelly, MD, PhD, FRCSC, FACS, Department of Neurosurgery and Medical Imaging,
University of Saskatchewan, Saskatoon, SK
“Recent advances in cerebrovascular and endovascular neurosurgery.”
3:00 Anthony G. Phillips, PhD, Scientific Director CIHR Institute of Neurosciences, Mental Health, and
Addiction, Department of Psychiatry, University of British Columbia, Vancouver, BC
“Positive developments for national funding programs of innovative research in basic and
clinical neurosciences.”
5:30 Cocktails – Bliss Fine Foods (1002 Broadway Ave)
6:00 Dinner – Bliss Fine Foods (1002 Broadway Ave)
Abstracts (in order of presentation)
Altschul Mini-Symposium (June 21)
Ina Weiner, “Tracing the development of psychosis and its prevention in an animal model.”
Prenatal and/or perinatal environmental adversities such as maternal malnutrition, stress or infection
have been associated with increased risk for of several adult onset neuropsychiatric disorders including
schizophrenia (SCZ), but how early genetic and/or environmental brain insults may lead to adult-onset
psychiatric disorders remains perplexing. One possibility is that early developmental damage leads to
late symptom appearance by altering postnatal brain maturation, raising the possibility that SCZ can be
prevented. Given the diagnostic, ethical, clinical and methodological challenges of pharmacological and
imaging studies prior to official diagnosis of SCZ, getting such information in humans remains a major
challenge. Animal neurodevelopmental models of SCZ are invaluable for investigating such questions. I
will present our recent studies that use longitudinal in vivo structural imaging in the prenatal immune
stimulation model that is based on the association of prenatal infection and increased risk for SCZ.
Pregnant rats were injected on gestational day 15 with the viral mimic polyriboinosinic-polyribocytidylic
acid (polyI:C) or saline. Male and female offspring were imaged and tested behaviorally on postnatal
days (PNDs) 35, 46, 56, 70 and 90. In other experiments, offspring of polyI:C- and saline-treated dams
received the atypical antipsychotic drugs (APDs) clozapine (7.5mg/kg) or risperidone (0.045mg/kg) in
two developmental windows: PND 34-47 and PND 48-61, and underwent behavioral testing and imaging
at adulthood. Prenatal polyI:C-induced interference with fetal brain development led to aberrant
postnatal brain development as manifested in structural abnormalities in the hippocampus, the
striatum, the prefrontal cortex and lateral ventricles (LV), as seen in SCZ. The specific trajectories
exhibited region-, age- and sex-specific deviations from normal trajectories, with more regions affected
as maturations progressed, and with females having delayed onset of pathology compared to males.
Increasing brain pathology was accompanied by development of behavioral abnormalities phenotypic of
SCZ, attentional deficit and hypersensitivity to amphetamine, with same sex difference. Hippocampal
volume loss and LV volume expansion as well as behavioral abnormalities were prevented in the
offspring of polyI:C mothers who received clozapine or risperidone during the asymptomatic period of
adolescence (PNDs 35-47). Administration at a later window, PNDs 48-61, exerted sex-, region- and
drug- specific effects. Our data show that prenatal insult leads to progressive postnatal brain pathology,
which gradually gives rise to "symptoms"; that treatment with atypical APDs can prevent both brain and
behavioral pathology; and that the earlier the intervention, the more pathological outcomes can be
prevented.
James I. Koenig, "Fetal stress exposure elicits enduring changes on the adult brain and behavior:
implications for schizophrenia.”
Stress is a known provocateur of many neuropsychiatric illnesses, including schizophrenia and
depression. Clinical epidemiology studies confirm a role for developmental stresses in the genesis of
schizophrenia, particularly if present during the fetal period. Maternal exposure to psychological
challenges, infections and malnutrition have adverse consequences on the developing fetus and all have
been associated with the etiology of schizophrenia. To learn more about the consequences of stress on
the developing fetus, my laboratory exposes pregnant female rats to a panel of unpredictable but mild
psychological stresses during a period that developmentally parallels the late first and early second
trimesters of human fetal brain development. In this presentation, we will discuss 1) the enduring
behavioral changes that arise as a consequence of this developmental stress exposure, 2) brain
mechanisms altered by the prenatal stress paradigm, 3) reversal of deficits by pharmacological agents
and 4) the implications of this research for the neurodevelopmental disorder, schizophrenia.
John G. Howland, “Antagonism of ELR-CXC chemokine receptors during pregnancy prevents the longterm cognitive changes caused by maternal immune activation in rats.”
Maternal infection during pregnancy is correlated with increased incidence of psychiatric disorders such
as schizophrenia in the offspring. Recent prospective epidemiological studies suggest that this
association may be the result of elevated levels of chemokines such as interleukin (IL)-8 in pregnancies
that result in schizophrenia. We chose to examine this association in rats using a well-established model
of maternal immune activation with the viral mimetic polyinosinic:polycytidic acid (polyI:C). We tested
two main hypotheses: (1) that polyI:C administration would acutely increase chemokine levels in
maternal and fetal tissues; (2) that antagonism of chemokine receptors at the time of polyI:C
administration would prevent the expected long-term cognitive changes in the offspring. Protein
analysis following polyI:C treatment revealed a significant increase in the chemokine GRO/KC (CXCL1), as
well as other proinflammatory cytokines including IL-1β, IL-6, and TNF-α, in maternal (serum, brain, lung,
and placenta) and fetal (brain, lung) after polyI:C injection. Behavioural experiments revealed that male
offspring from polyI:C treated dams displayed significantly impaired prepulse inhibition (before and
after puberty) and set-shifting, consistent with some cognitive symptoms of schizophrenia. Offspring
from dams treated with the ELR-CXC receptor antagonist G31P alone displayed behavior on the PPI and
set-shifting tasks similar to that of controls. Remarkably, polyI:C offspring treated with G31P also
displayed behavior similar to that of controls. The present findings suggest that pharmacological
blockade of ELR-CXC chemokine receptor signaling during an inflammatory event in pregnancy prevents
the long-term alterations in cognition typically observed in the offspring. Thus, this strategy may serve
as a novel approach to prevent psychiatric disorders caused by maternal infection.
Aaron J. Gruber, “Brain insults early in life alter cortical activity and impair economic decision-making in
rats.”
Making good decisions often requires attention to salient stimuli and the use of past experience with
rewards and punishments to alter future choices. These processes involve interactions among several
cortical and subcortical brain structures including the frontal cortex, basal ganglia and dopaminereleasing neurons. Brain insults early in life can impair decision-making by altering neural function in
these systems. This presentation will highlight some recent work with neurodevelopmental rodent
models of schizophrenia that reveal impaired behavioral flexibility and dysregulation of neural signaling
in prefrontal cortex. Models based on different pathogeneses reveal similar desynchronization and
disinhibition of cortical neural activity, suggesting common impairments of information processing that
may be useful for inferring functional deficits in the human disease.
Sylvain Williams, “Investigating early anatomical and functional changes in the
hippocampal GABAergic network in a prenatal infection model.”
It is now well established that GABAergic neurotransmission is impaired in schizophrenia. However, it
remains unclear if these changes occur early during development and how they impact overall network
activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic,
polyriboinosinic–polyribocytidilic acid (polyI:C), a model based on epidemiological evidence that an
immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring.
We found that prenatal infection reduced the density of parvalbumin- but not somatostatin-positive
interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early
during postnatal development of offspring (PND 16-21). Furthermore, using an intact hippocampal
preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Using optogenetic
techniques in the complete hippocampal preparation, we also show that the parvalbumin, but not
somatostatin interneurons, are intimately responsible for generating theta oscillations. Taken together,
these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is
associated with a significant alteration in network function. Furthermore, given the role of theta
rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network
function very early in development that could contribute to cognitive deficits observed later in the
disease.
Neuroscience Research Day (June 22)
Lisa E. Kalynchuk, “Reelin and the pathogenesis of major depression”
Reelin is an extracellular matrix protein that plays an important role in cell migration, dendritic spine
formation, and synaptic plasticity within the adult hippocampus. We have been working on the idea that
a deficit in hippocampal reelin signaling may be involved in the pathogenesis of depression. In this talk, I
will describe the results of three experiments designed to investigate this idea. First, I will show that
repeated exposure to corticosterone, which robustly increases depression-like behavior in rats,
decreases the number of reelin+ pyramidal-basket cells in the subgranular zone of the dentate gyrus and
decreases the maturation rate of newborn dentate granule cells. Importantly, these results are reversed
by the tricyclic antidepressant imipramine. Second, I will show that the progressive development of
depression-like behavior in corticosterone-treated rats over time is paralleled by decreases in
hippocampal reelin expression and granule cell morphology. And finally, I will show that heterozygous
reeler mice with only 50% of normal brain levels of reelin are much more susceptible to the
depressogenic effects of corticosterone than their wild-type counterparts. Together, these results
support our hypothesis that reelin is involved in the pathogenesis of depression and suggest that reelin
may be an important biological target for the development of novel antidepressants.
Josef Buttigieg, “Hypoxia and Hypercapnia sensing by pulmonary neuroendocrine cells.”
The airway epithelium of the mammalian lung contains specialized pulmonary neuroendocrine cells
(PNEC), distributed as solitary cells and as innervated clusters termed neuroepithelial bodies (NEB). Both
PNEC and NEBs express neural and endocrine phenotypes, including the synthesis and release of amine
(5-HT) and a variety of neuropeptides. These cells are thought to act as peripheral chemosensors and
function to match lung perfusion to ventilation rates. While the mechanism of hypoxia/hypercapnia
sensing is poorly understood in PNEC/NEB, we have evidence that links the chemosensing properties in
these cells to a membrane delimited mechanism and will be described in this talk.
Jack R. Gray, “Neural control of adaptive behaviour: Good things come in small packages.”
Successful navigation through complex environments requires precise detection and assessment of
salient sensory information as well as coordinated outputs that control muscles and appendages. We
study the highly tractable insect flight system to address questions of how sensory information (vision)
modulates steering. We describe behaviour, kinematics and sensory processing during presentation of
visual stimuli in virtual space. Wing kinematics and muscle activity predict steering and identified
motion-sensitive interneurons can encode complex visual motion associated with dynamic behaviour.
Ongoing experiments that close the virtual feedback loop will allow us to better understand ubiquitous
fundamental processes of sensorimotor integration and behaviour.
Ron Borowsky, “Strategic effects of instructions on the ventral-lexical reading stream: converging
evidence from neuroimaging and reaction time.”
Neurobiology of reading research has yet to explore whether reliance on the ventral-lexical stream
during word reading can be enhanced by the instructed reading strategy, or whether it is impervious to
such strategies. We examined Instructions: name all versus name words, Word Type: regular words
versus exception words, and Word Frequency (WF) in print in an experiment while measuring the
functional magnetic resonance imaging blood oxygenation level dependent (fMRI BOLD) function and
overt naming reaction time (RT) simultaneously. Instructions to name words increased overall reliance
on the ventral-lexical stream, as measured by visible BOLD activation and the WF effect on RT, with
regular words showing the greatest effects as a function of this reading strategy. Furthermore, the
pattern of joint effects of these variables on RT supports the notion of cascaded, not parallel,
processing. These results can be accommodated by dual-stream cascaded models of reading, and
present a challenge to single-mechanism parallel processing models.
Darrell D. Mousseau, “What is the intersection between depression and dementia?”
Depression and Alzheimer disease (AD)-related dementia are two important global mental health
challenges. Depression is associated with an increased risk of developing AD, yet the molecular
commonality remains unclear. The recent literature suggests that it is the treatment of the depression
that could be triggering AD-like changes within the cell/brain. We are finding that some of the more
commonly prescribed antidepressants can cause the intracellular accumulation, and misfolding, of the
AD-related amyloid peptide in cell cultures. Changes in prescription practice based on identifying which
pharmaceuticals facilitate this effect could help to avoid the onset of AD in vulnerable individuals.
Michael E. Kelly, “Recent advances in cerebrovascular and endovascular neurosurgery.”
Cerebrovascular disorders represent some of the most challenging medical problems. New techniques
are being developed to treat these patients. They include surgical, endovascular and radiosurgery
therapies. The relevance of basic science and translation research and its impact on the cerebrovascular
patient’s treatment will also be discussed.