2004 Neurocience Poster Day - Program in Neuroscience ...

NEUROSCIENCE POSTER DAY - Thursday, April 29, 2004
SCHEDULE
11:00 - Noon: Registration (free), Poster set up and viewing
Medical Sciences Building, Alumni Lounge
First Undergraduate Neuroscience Specialist’s Posters
Separate undergraduate poster viewing area: MacLeod Auditorium
Balcony
Noon - 1:00pm:
Pizza lunch
1:00 - 3:00pm: Poster viewing and judging
Medical Sciences Building, Alumni Lounge and MacLeod
Auditorium Balcony
3:00 -4:00pm: DR. JOE TSIEN, Department of Molecular Biology, Princeton
University
"Integrated analysis of memory processes in the brain"
Medical Sciences Building, Rm 2172
Co-sponsored by the Hospital for Sick Children
Poster Day Organizers:
John Yeomans, Program in Neuroscience Acting Director
Pat Reed, PIN Secretary
Martin Ralph, Undergraduate Neuroscience Program Coordinator

GRADUATE POSTERS
1 Asrar, Suhail*
Department of Physiology, University of Toronto; Program of Brain and Behaviour,
Hospital for Sick Children
AMPA-DEPENDENT LTP: A LESSER KNOWN FORM OF PLASTICITY
2 Bagshaw, Rick D. * 1,3 , Callahan, John W. 2,3 , Mahuran, Don J. 1,3
1. Dept. of Laboratory Medicine and Pathobiology; 2. Dept. of Biochemistry, University
of Toronto; 3. Metabolism Programme, Research Institute, The Hospital for Sick
Children, Toronto, Canada
PROTEOMICS OF THE LYSOSOMAL MEMBRANE REVEALS DIVERSE ORIGINS
OF THE LYSOSOME
3 Bedard, Anne-Claude* & Tannock, Rosemary
Institute of Medical Science & Program in Neuroscience, The University of Toronto
Brain & Behaviour Research Program, The Hospital for Sick Children
BENEFICIAL EFFECTS OF METHYLPHENIDATE ON VERBAL WORKING
MEMORY IN CHILDREN WITH ADHD
4 Behl, Pearl * & Black, Sandra - CANCELLED
Institute of Medical Science
EXAMINATION OF THE LONGITUDINAL EFFECTS OF CHOLINERGIC THERAPY ON
ALZHEIMER’S DISEASE (AD)(ELECT-AD)
5 Bercovici, Eduard
1,2 *, Cortez, M.A. 2 , Snead III, O. Carter 1,2
1. Institute of Medical Science, University of Toronto, Toronto, Canada; 2. Brain and
Behaviour Program, Division of Neurology, The Hospital for Sick Children Department
of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada
SEROTONIN DIRECTLY MODULATES AY-9944 INDUCED ATYPICAL
ABSENCE SEIZURES
6 Bezchlibnyk, Yarema B.
1,2 , Young, L. Trevor 1,2 , Chen, Biao 2 , Wang, Jun-Feng 1,2 and
MacQueen, Glenda M. 2
1. Mood and Anxiety Program, Centre for Addiction and Mental Health, Department of
Psychiatry, University of Toronto, Toronto, Ontario; 2. Department of Psychiatry and
Behavioural Neuroscience, McMaster University, Hamilton, Ontario
CREB PHOSPHORYLATION IN THE AMYGDALA OF SUBJECTS WITH MOOD
DISORDERS
7 Blech-Hermoni, Yotam* & Seltzer, Ze’ev
University of Toronto Centre for the Study of Pain, Faculty of Dentistry
A LOCUS ON CHROMOSOME 7 PLAYS A ROLE IN NEUROPATHIC PAIN IN HA
AND LA RATS AND IS ORTHOLOGOUS TO PUTATIVE PAIN QTL PAIN1 IN THE
MOUSE
2

8 Bollig, Carmen M. 1 , Bressmann, Tim 1 , Uy, Catherine 1 , Thind, Parveen 1 , Irish, Jonathan
C. 2
1 Graduate Department of Speech-Language Pathology, University of Toronto;
2 Department of Otolaryngology/Head and Neck Surgery, University Health Network,
University of Toronto
EVALUATION OF TONGUE SHAPES WITH 3-DIMENSIONAL ULTRASOUND
IMAGING IN GLOSSECTOMY PATIENTS PRE- AND POST-SURGICALLY
9 Caraiscos, Valerie B. 1 *, You-Ten, Kong E. 2 , Newell, J. Glen 3 , Elliott, Erin M. 1 , Rosahl,
Thomas W. 5 , Wafford, Keith A. 5 , MacDonald, John F. 3,4 and Orser, Beverley A. 1,2,3,6
1 Institute of Medical Science, Departments of 2 Anesthesia, 3 Physiology and
4 Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada; 5 Merck
Sharp & Dohme Research Laboratories, Neuroscience Research Center, Terlings Park,
Harlow, Essex, United Kingdom; 6 Department of Anesthesia, Sunnybrook & Women’s
College Health Sciences Centre, Toronto, Ontario, Canada
ANESTHETICS SELECTIVELY MODIFY A NOVEL FORM OF GABAERGIC
INHIBITION
10 Cheung, Joyce & Wojtowicz, J. Martin
Department of Physiology, University of Toronto
AGE-RELATED CHANGES IN THE PRODUCTION AND MIGRATION OF NEW
NEURONS IN THE RAT OLFACTORY SYSTEM
11 Chiu, Mary* & Orser, Beverley
Department of Physiology, University of Toronto
LOCALIZATION OF α5-CONTAINING GABA A RECEPTORS IN THE
HIPPOCAMPUS
12 Cohn, Mélanie* 1 , Levine, Brian 1,2,3 , Black, Sandra E. 2,3,4 , Richards, Brian 5 , Kaufman,
Yakir 6 , Freedman, Morris 2,6 , and Moscovitch, Morris 1,3
Departments of 1 Psychology/ 2 Medicine (Neurology), University of Toronto; 3 Rotman
Research Institute at Baycrest Centre for Geriatric Care; 4 Sunnybrook and Women’s
College Health Sciences Centre; Departments of 5 Psychology/ 6 Behavioural Neurology,
Baycrest Centre for Geriatric Care, Toronto, Ontario
SEMANTIC AND EPISODIC MEMORY LOSS IN A CASE OF WHIPPLE’S
DISEASE ENCEPHALOPATHY
13 Cunic, D.I. 1,2 *, Paradiso, G. 1,2 , Kwan, C. 2 , Sailer, A. 1,2 , Moro, E. 1,2 , Poon, Y. 1,2 , Molnar,
G. 1,2 , Gunraj, C. 1,2 , Lang, A.E. 1,2 , Lozano, A.M. 2, 3 , Chen, R. 1,2
1 Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada; 2 Toronto
Western Research Institute, Toronto, Ontario, Canada; 3 Division of Neurosurgery,
Toronto Western Research Institute, Toronto, Ontario, Canada
SOURCE GENERATORS OF EVOKED POTENTIALS FROM SUBTHALAMIC
NUCLEUS DEEP BRAIN STIMULATION
3

14 Elliott, Erin M. 1 *, MacDonald, John F. 2,3 , and Orser, Beverley A. 1,2,4,5
1 Institute of Medical Science, Depts. of 2 Physiology, 3 Pharmacology, 4 Anesthesia, Univ.
of Toronto, Toronto, ON, Canada, M5S 1A8; 5 Dept. of Anesthesia, Sunnybrook &
Women’s College HSC, Toronto, ON, Canada, M4N 3M5
TONIC BUT NOT SYNAPTIC INHIBITORY CONDUCTANCE IN MURINE
HIPPOCAMPAL NEURONS IS ENHANCED BY LOW CONCENTRATIONS OF THE
β2/3 SUBUNIT SELECTIVE ANESTHETIC ETOMIDATE
15 Fawcett, A.P. 1 *, Moro, E. 2 , Lang, A.E. 2 , Lozano, A.M. 3 , Hutchison, Wm.D. 1,3
1. Dept. of Physiology 2. Dept. of Medicine, Division of Neurology 3. Dept. of Surgery,
Div. of Neurosurgery, University of Toronto, Toronto, Ontario, Canada
PALLIDAL DEEP BRAIN STIMULATION (DBS) INFLUENCES BOTH REFLEXIVE
AND VOLUNTARY SACCADES IN HUNTINGTON’S DISEASE
16 Giannoylis, Irene* 1 , Nelson, Aimee J. 3 , Staines, Richard W. 3,4 , McIlroy, William E. 2,3,4
1. Department of Physiology, University of Toronto; 2. Graduate Department of
Rehabilitation Science, University of Toronto; 3. Sunnybrook & Women’s College
Health Science Center, University of Toronto; 4. Kinesiology & Health Science, York
University, Toronto, ON, Canada
EFFECTS OF PERCEIVED EFFORT DURING A MOTOR TASK MEASURED
USING FMRI
17 Glazer, P. M.* 1 , Quant, S. 2 , Maki, B. E. 2, 5 , & McIlroy, W. E. 1,2,3,4
1 Graduate Department of Rehabilitation Science, 2 Institute of Medical Science,
3 Department of Physical Therapy, 4 Toronto Rehab Institute, University of Toronto;
5 Centre for Studies in Aging, Sunnybrook and Women’s College Health Sciences Centre,
University of Toronto
THE EFFECT OF VERBAL FLUENCY TASK ON BALANCE CONTROL
18 Guy, Allison* & Broussard, Dianne
Department of Physiology, University of Toronto, Canada
Toronto Western Research Institute, University of Toronto, Canada
INVESTIGATION OF THE ROLE OF IONOTROPIC GLUTAMATE RECEPTORS IN
SHORT-TERM PLASTICITY IN THE MEDIAL VESTIBULAR NUCLEI
19 Ho, Stephanie K.Y. 1 *, Kovacevic, Natasha 2 , Chen, Josette X. 2 , Henkelman, Mark R. 2 ,
Henderson, Jeffrey T. 1
1
Department of Pharmaceutical Sciences, University of Toronto, 2 Mouse Imaging
Centre, Hospital for Sick Children, Toronto
ROLE OF EPHB RECEPTORS IN MURINE CNS AXON GUIDANCE
20 Huang, Juan 1 , Wu, Xihong 1 , Yeomans, John 2 , Li, Liang 1,2
1 Department of Psychology, Speech and Hearing Research Center, Peking University,
Beijing, China, 100871
2 Department of Psychology, Centre for Research on Biological Communication Systems,
University of Toronto, Toronto, Ontario, Canada M5S 3G3
EFFECTS OF TETANIC STIMULATION OF THE AUDITORY THALAMUS OR
AUDITORY CORTEX ON ACOUSTIC STARTLE RESPONSES IN AWAKE RATS
4

21 Hwang, Rudi 1 *, Deluca, V. 1 , Masellis, M, 1 Mueller, D. 1 , Czobor, P. 2 , Volavka, J. 2 ,
Lieberman, J.A. 3 , Meltzer, H.Y. 4 , Kennedy, J.L. 1
1. Neurogenetics Section, Centre for Addiction and Mental Health (CAMH), University
of Toronto; 2. Nathan S. Kline Institute for Psychiatry Research; 3. University of North
Carolina at Chapel Hill; 4. Case Western Reserve University
INVESTIGATING THE EFFECT OF DOPAMINE D1 & D2 RECEPTOR GENE
POLYMORPHISMS ON ANTIPSYCHOTIC TREATMENT RESPONSE
22 Labrie, Viviane* 1,2,3 , Lipina, Tatiana 3 , Roder, John 1,2,3
1 Collaborative Program in Neuroscience, 2 Institute of Medical Science, 3 Samuel
Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
THE BRAIN GLUTAMATERGIC SYSTEM AS A TARGET FOR NOVEL
CLASS OF NEUROLEPTICS
23 Lau, A.*, Arundine, M., Tymianski, M.
Department of Physiology, University of Toronto, Toronto, Canada;
Division of Cellular and Molecular Biology, Toronto Western Research Institute,
Toronto, Canada
SIN-1 INDUCED NITRATION INHIBITS CASPASE-3 ACTIVITY IN THE
STAUROSPORINE MODEL OF CLASSICAL APOPTOSIS IN NEURONS
24 Levy, Naama 1,2,3 *, Black, Sandra 1-5 , Caldwell, Curtis 1,2 , Lobaugh, Nancy 1,2,4 , Bocti,
Christian 1,4 - CANCELLED
Cognitive Neurology Unit and Imaging Research, Sunnybrook and Women's College
Health Sciences Centre 1 , Toronto, Ontario, Canada; Institute of Medical Science 2 ,
Program in Neuroscience 3 , and Department of Medicine/Division of Neurology 4 ,
University of Toronto; Rotman Research Institute and Baycrest Centre for Geriatric Care 5
IMPACT OF CEREBROVASCULAR COMORBIDITY ON SPECT PERFUSION
IMAGING AND EXECUTIVE FUNCTION IN ALZHEIMER'S DISEASE
25 McDonald, Heather* & Wojtowicz, J. Martin
Department of Physiology, University of Toronto
AGE-RELATED DECREASE IN HIPPOCAMPAL NEUROGENESIS: POSSIBLE
IMPLICATIONS FOR COGNITIVE DECLINE DURING AGING
26 Miller, R.C.* 1,5 , McIlroy, W.E. 1,2,3,6 , Mikulis, D.J. 7 , Jurkiewicz, M.T.* 3,7 , Popovic,
M.R. 4,5,6 , and Verrier, M.C. 1,2,3,6 .
1. Department of Rehabilitation Science, 2. Physical Therapy, 3. Physiology, 4. Institute
of Biomaterials and Biomedical Engineering, University of Toronto; 5. Rehabilitation
Engineering Laboratory, 6. Toronto Rehabilitation Institute: Lyndhurst Center; 7.
Medical Imaging, Toronto Western Hospital; Toronto, Ontario, Canada
NEUROMUSCULAR RESTORATIVE THERAPY (NRT)
27 Moore, Kathryn J. 1,2 & Shoichet, Molly S. 1,2,3
Department of Chemical Engineering and Applied Chemistry 1 ; Institute of Biomaterials
and Bioengineering 2 ; Department of Chemistry 3
COMBINED GRADIENTS OF NEUROTROPHIC FACTORS WORK IN SYNERGY
TO GUIDE NEURITE OUTGROWTH
5

28 Niechwiej-Szwedo, E.* 1 , Gonzalez, E. 2,3,4 , Steinbach, M.J. 1,2,3,4
1 Institute of Medical Science, 2 Department of Ophthalmology and Vision Science,
University of Toronto; 3 Vision Science Research Program, Toronto Western Hospital;
4 Centre for Vision Research, York University
LOCALIZATION OF TARGETS IN DEPTH WITH ALTERED AFFERENT
FEEDBACK
29 Rivkin, Elena* & Cordes, Sabine
Department of Molecular and Medical Genetics
FORWARD GENETIC RECESSIVE SCREEN TO IDENTIFY NOVEL MOUSE
MUTANTS WITH DEFECTS IN HINDBRAIN PATTERNING
30 Saab, Béchara 1,2 *, Georgiou, John 2 , Roder, John 1,2
1 Collaborative Program in Neuroscience, Molecular & Medical Genetics Department,
University of Toronto, 2 Samuel Lunenfeld Research Institute, Mount Sinai Hospital,
Toronto, Canada
THE C-TERMINAL PEPTIDE OF THE CALCIUM SENSOR, NCS-1, MODULATES
SHORT-TERM SYNAPTIC PLASTICITY IN THE MOUSE HIPPOCAMPUS
31 Seminowicz, D.A.*, Mikulis, D.J., Davis, K.D.
Institute of Medical Science
CORTICAL NOCICEPTIVE ACTIVITY IS ALTERED DURING COGNITIVE
ENGAGEMENT
32 Setnik, Beatrice 1,2 * & Nobrega, José N. 1,2
1
Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, ON,
Canada; 2 Department of Pharmacology, University of Toronto, Toronto, ON, Canada
SEX-DEPENDENT UPREGULATION OF CORTICAL TrkB RECEPTOR mRNA
LEVELS IN THE LEARNED HELPLESSNESS MODEL OF DEPRESSION
33 Shao, Li, Sun, Xiujun, Xu, Li, Young, L.Trevor and Wang, Junfeng
Centre for Addiction and Mental Health, and Department of Psychiatry,
University of Toronto, Ontario, Canada
ENDOPLASMIC RETICULUM STRESS PROTEINS: A TARGET IN COMMON FOR
MOOD STABILIZERS LITHIUM AND VALPROATE IN NEURONAL CELLS
34 Sibley, K.M.* 1, 3 , Tang, A. 1-3 , Brooks, D. 1-3 , McIlroy, W.E. 1-3
1. Graduate Department of Rehabilitation Science, 2. Department of Physical Therapy,
University of Toronto, 3. Toronto Rehabilitation Institute, Toronto, Ontario
NEUROMUSCULAR AND CARDIOVASCULAR RESPONSES TO NOVEL
PEDALING STRATEGIES IN HEALTHY PARTICIPANTS
35 Stevens, W. Dale 1 *, Cron, Greg O. 2 , Pappas, Bruce A. 3 , Santyr, Giles E. 2 , Grady, Cheryl
L. 1
1. Rotman Research Institute, University of Toronto, Toronto, ON; 2. Department of
Physics, Carleton University, Ottawa, ON; 3. Institute of Neuroscience, Carleton
University, Ottawa, ON
QUANTIFICATION OF CEREBRAL, RETINAL, AND VERTEBRAL BLOOD FLOW
IN RAT MODELS OF ISCHEMIA: A MRI STUDY
6

36 Vessal, Mani* 1,2,3,4 , Dugani, Chandrasagar B. 4 , Solomon, Dianand A. 4 , Burnham, W.
McIntyre 1,2,3,5 , Ivy, Gwen O 4 .
Institute of Medical Science 1 , Program in Neuroscience 2 , and Bloorview Epilepsy
Research Program 3 , University of Toronto, Toronto; Centre for the Neurobiology of
Stress 4 , University of Toronto at Scarborough, Scarborough; Department of
Pharmacology 5
GLIOGENESIS IN THE PIRIFORM CORTEX OF KINDLED SUBJECTS: A
QUANTITATIVE ANALYSIS OF FULLY KINDLED BRAINS
37 Xu, J.*, Xue, S., Lei, G., Kwan, C.L., Yu, X.-M.
Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
THE ROLE OF C-TERMINAL SRC KINASE (CSK) IN THE REGULATION OF
NMDA RECEPTORS
38 Zai, Gwyneth* 1,2 , King, Nicole 2 , Burroughs, Eliza 4 , Barr, Cathy L. 1,3,5 , Kennedy, James
L. 1,2,3,5 , Richter, Peggy 3,4
1 Institute of Medical Science, University of Toronto; 2 Neurogenetics Section, Centre for
Addiction and Mental Health; 3 Department of Psychiatry, University of Toronto;
4 Anxiety Disorders Clinic, Centre for Addiction and Mental Health; 5 The Toronto
Hospital – Western Division, Department of Psychiatry, University of Toronto
QUANTITATIVE TRAIT ANALYSIS OF THE GAMMA-AMINOBUTYRIC ACID
BETA RECEPTOR 1 GENE IN OBSESSIVE-COMPULSIVE DISORDER
39 Zhao, Xiao-Han* 1,2 , Xin, Wen-Kuan 1,2 , Xu, Jindong 1,2 , Kwan, Chun L. 1,2 , Zhu, Kang-
Min 1,2 , Cho, Jae-Sung 1,2 , Duff, Missy 1,2 , Ellen, Richard P. 1,3 , McCulloch, Christopher
A.G. 1,3 and Yu, Xian-Min 1,2
1. Faculty of Dentistry, 2. Centre for Addiction and Mental Health, 3. The CIHR Group
in Matrix Dynamics, University of Toronto, Toronto, ON, Canada
CRITICAL CONTROL POINT: RECRUITING N-METHYL-D-ASPARTATE (NMDA)
RECEPTOR-MEDIATED TOXICITY
7

UNDERGRADUATE POSTERS
40. Capano, Lucia
Undergraduate Neuroscience Specialist Program
INVESTIGATION OF DNA VARIANTS IN THE 5’-REGULATORY REGION OF
THE DRD1 GENE IN ATTENTION DEFICIT/HYPERACTIVITY DISORDER
41. Chan, E. 1 , Kovačević, N. 2 , Henderson, J. T. 3
1. Neuroscience Specialty, University of Toronto; 2. Department of Pharmceutical
Sciences, University of Toronto; 3. Mouse Imaging Centre, Hospital for Sick Children
THE DEVELOPMENT OF AN MRI BASED EXPERT SYSTEM AND 3D SURGICAL
MRI/CT ATLAS FOR 129/SvImJ AND C57BL6 INBRED MOUSE STRAINS
42. Cheung, Joyce
Department of Physiology
AGE-RELATED CHANGES IN THE PRODUCTION AND MIGRATION OF NEW
NEURONS IN THE RAT OLFACTORY SYSTEM
43. Clarke, Laura, Georgiou, John, Salter, Michael, Roder, John
The Samuel Lunenfeld Research Institute
ROLES OF Src TYROSINE KINASE IN HIPPOCAMPAL SYNAPTIC PLASTICITY
44. Ding, Hoi Ki, Ko, Shanelle, Shum, Fanny, Zhuo, Min
Department of Physiology, Centre for the Study of Pain, University of Toronto
A THERMAL-BASED ACTIVE ESCAPE/AVOIDANCE PARADIGM WITHOUT
FEAR
45. Hirshhorn, Marnie
Undergraduate Neuroscience Specialist Program
ASSESSING THE PRESENCE OF OSCILLATORY ACTIVITY IN THE THALAMUS
OF PARKINSON’S DISEASE PATIENTS
46. Ng, Karen
Undergraduate Neuroscience Specialist Program
INVESTIGATING THE ROLE OF THE m5 CHOLINERGIC RECEPTOR IN BRAIN
STIMULATION REWARD USING PHAMACOLOGICAL AND
ELECTROPORATION TECHNIQUES
47. Rizvi, Sakina
Undergraduate Neuroscience Specialist Program
MEMORY DEFICITS AMONG PERSONS WITH SCHIZOPHRENIA: UTILITY OF
THE NINE-BOX MAZE TASK
48. Salmasi, Giselle Ghazal
Neuroscience Research, Department of Laboratory Medicine and Pathobiology,
Sunnybrook and Women’s College Health Sciences Centre, University of Toronto
DRAINAGE OF CEREBROSPINAL FLUID INTO EXTRACRANIAL LYMPHATICS
IN RATS AND MICE REVEALED BY INTRACISTERNAL INJECTION OF
MICROFIL
8

49. Watts, Jeff
Undergraduate Neuroscience Specialist Program
CAN DIFFERENCES IN THE Ca 2+ SENSOR EXPLAIN DIFFERENCES IN
QUANTAL OUTPUT BETWEEN CRAYFISH TONIC AND PHASIC CELLS A
MONTE CARLO MODEL
50. Wong, Fiona
Undergraduate Neuroscience Specialist Program
H1, A STABLE HEPOXILIN ANALOG, DOES NOT ENHANCE NEURITE
OUTGROWTH OR REGENERATION AFTER INJURY IN RAT
PHEOCHROMOCYTOMA CELLS OR PRIMARY HIPPOCAMPAL NEURONS IN
VITRO
51. Wong, J.S., Hutchison, W.D.
Department of Physiology, Faculty of Arts and Science and Faculty of Medicine,
University of Toronto, Ontario, Canada
6-HYDROXYDOMAPINE REDUCES MOTOR BEHAVIORS OF RATS AND
INDUCES DISTINCT FIRING PATTERNS IN MULTI-UNIT RECORDINGS OF THE
RODENT GLOBUS PALLIDUS
52. Yum, Jennie
Undergraduate Neuroscience Program, University of Toronto, Toronto, Ontario, Canada,
M5S 3G3
SHORT-TERM DEPRESSION AT THE DEVELOPING CALYX OF HELD
SYNAPSE: EVIDENCE FOR HETEROSYNAPTIC INHIBITION MEDIATED BY
PRESYNAPTIC GABA B RECEPTORS
9

GRADUATE POSTER ABSTRACTS
1. Asrar, Suhail*
Department of Physiology, University of Toronto; Program of Brain and Behaviour, Hospital for
Sick Children
AMPA-DEPENDENT LTP: A LESSER KNOWN FORM OF PLASTICITY
A strong majority of studies conducted involving synaptic plasticity (which is thought to be
important in learning and memory) revolve around NMDA-dependent forms of plasticity.
However, certain studies have revealed that NMDA-independent forms of plasticity may be
induced in the hippocampus of mice where the AMPA GluR2 subunit has been knocked out.
Most AMPA receptors are normally not significantly permissive to calcium due to the activity of
the GluR2 subunit, and the knocking-out of this subunit leads to the formation of AMPA
receptors that are calcium permeable. The study of these mutant receptors is important for several
reasons. Firstly, there are inter-neurons present in the hippocampus that are also permeable to
calcium but are difficult to study, and research in calcium permeable AMPA receptors may shed
more light on the way that these inter-neurons function. Secondly, under pathological conditions,
calcium influx from calcium permeable AMPA receptors has shown to have an important role in
the adverse mechanisms that ultimately lead to cell death.
The precise mechanisms involved in this NMDA-independent form of plasticity remain unknown,
and may involve a variety of signaling factors including PKA, PKC and CaMKII. The latter has
shown to be particularly important in numerous studies implicating its role in NMDA-dependent
forms of plasticity. Therefore, to test the possibility that CaMKII may play an important role in
AMPA-dependent plasticity, we used the CaMKII inhibitor KN-62 in the presence of the NMDA
blocker APV in electrophysiological studies where AMPA-dependent LTP (long term
potentiation) was induced tetanically under field recordings measured in the CA1 region of the
hippocampus. Surprisingly, our preliminary data suggests that CaMKII may not have a significant
role in AMPA-dependent LTP induced in mutant mice. These results suggest that a distinct
mechanism may operate for AMPA receptor-induced synaptic plasticity.
10

2. Bagshaw, Rick D.* 1,3 , Callahan, John W. 2,3 , Mahuran, Don J. 1,3
1. Dept. of Laboratory Medicine and Pathobiology; 2. Dept. of Biochemistry, University of
Toronto; 3. Metabolism Programme, Research Institute, The Hospital for Sick Children, Toronto,
Canada
PROTEOMICS OF THE LYSOSOMAL MEMBRANE REVEALS DIVERSE ORIGINS OF
THE LYSOSOME
Lysosomes are dynamic, endocytic subcellular compartments which contribute to degradation
and recycling of cellular material. From our proteomic model of lysosomes (rat liver Triton
WR1339-filled lysosomes) we have identified 254 unique proteins thus far in the lysosomal
membrane. We have used a combination of 2D-IPG-PAGE:mass spectrometry and Ion-exchange
chromatography:LC-MS/MS as protein identification strategies. About half of the proteins
identified are known constituents of the endosomal/lysosomal system and proteins involved in
membrane trafficking, and 25% of proteins match to unknown cDNAs. The remaining proteins
are those originally associated with other cellular compartments such as Golgi, ER, and Plasma
membrane indicating diverse origins of the lysosomal membrane. The unexpected identification
of the Alzheimer’s disease-associated γ-secretase complex (Nicastrin, Presenilin, and APP),
allowed us to characterize its enrichment and acidic-pH optimum enzymatic activity in the
lysosomal membrane. An unknown protein identified in the integral membrane protein fraction
contains domains highly similar to those from the ARF family of G-proteins involved in protein
trafficking. It localizes with lysosomal markers by immunofluorescence, and is expressed in all
human tissues, suggesting that it has a fundamental role in the endosomal/lysosomal system.
Characterizing novel lysosomal proteins will help elucidate the roles of the lysosome in cell
biology.
11

3. Bedard, Anne-Claude* & Tannock, Rosemary
Institute of Medical Science & Program in Neuroscience, The University of Toronto
Brain & Behaviour Research Program, The Hospital for Sick Children
BENEFICIAL EFFECTS OF METHYLPHENIDATE ON VERBAL WORKING MEMORY IN
CHILDREN WITH ADHD
Objective: To investigate the effect of methylphenidate (MPH) on verbal working memory, as
measured by the digit span subtests of the WISC-PI, in children with Attention-
Deficit/Hyperactivity Disorder (ADHD). Verbal working memory is a core component of
working memory that has been shown to be impaired in ADHD. Given the lack of precision in the
behavioral phenotype of ADHD, we examined whether individual differences within the
inattention dimension were associated with patterns of treatment response in verbal working
memory.
Methods: A clinic-referred sample of school-aged children with a confirmed DSM-IV diagnosis
of ADHD (n=100) completed a test of verbal span and working memory in an acute, randomized,
placebo-controlled, crossover trial with three single fixed doses of MPH. The sample was divided
into mildly inattentive and severely inattentive subgroups.
Results: MPH significantly improved performance on the verbal working memory task. Severely
inattentive children were characterized by a positive cognitive response to stimulant medication
compared to mildly inattentive children.
Conclusions: These findings provide insight into potential mechanisms underlying individual
differences in cognitive functioning and treatment response in ADHD, which in turn may
facilitate more targeted treatments.
12

4. Behl, Pearl * & Black, Sandra
Institute of Medical Science
EXAMINATION OF THE LONGITUDINAL EFFECTS OF CHOLINERGIC THERAPY ON
ALZHEIMER’S DISEASE (AD)(ELECT-AD)
Cholinergic neurons in the basal forebrain project diffusely to the cortical and limbic structures of the
brain and are involved in many aspects of cognitive function. These nuclei have strong interconnections
with the limbic system and are a major source of cholinergic output to the hippocampus and the cerebral
cortex. The basal forebrain nuclei are targeted in AD and deterioration of these neurons leads to a
progressive decline in the brain levels of Acetylcholine. Given this gradual cortical cholinergic
denervation, therapy that would enhance the synaptic concentrations of Acetylcholine would seem
rational and several cholinesterase inhibitors have now been on the market for symptomatic treatment of
AD, some for over 10 years. No other effective treatments have yet emerged, although research into better
therapeutics on AD continues. It is important therefore to better understand the effects of cholinergic
therapy on cognitive and behavioral functioning over time. In order to appreciate the effects of these
agents, it is necessary, however, to know about the natural history of the cognitive and behavioral
impairments in AD.
Only one study has compared the natural history of cognitive decline in untreated AD patients over one
year to the progression seen in patients on cholinesterase inhibitors. Patients on cholinesterase inhibitors
were better at one year both cognitively and functionally compared to those who had never had treatment.
This is promising, but more studies, especially with more detailed assessments of cognitive domains are
certainly needed, particularly longitudinal follow-up of executive functions that especially impact on
instrumental activities of daily living. Given that AD has a mean duration of 8 to 9 years, it is essential to
assess the potential of cholinesterase inhibitors over longer timer periods in order to evaluate whether
these drugs really do make a lasting difference to patients. Most studies have only looked at short-term
benefits in cognition, behavior and function within a 6-month, double blind, randomized placebo
controlled design, since placebo-controlled trials are very difficult to do over periods longer than 6
months or one year in the AD population. In fact, the relative success of the cholinergic agents now
means that a placebo group is unethical. Hence, case-control studies of patients in the untreated era
compared to post-treatment era may realistically be the only design that is feasible to understand the
longer-term effects of this new class of drug. Purpose: This study, therefore, aims to assess the
longitudinal effects of treatment with cholinesterase inhibitors compared to no treatment in matched
cohorts of patients with AD enrolled in a longitudinal observation study either prior to when treatment
became available or after treatment became a common clinical option. Methods: Probable AD patients
were recruited from the Cognitive Neurology Memory clinic at Sunnybrook and Women’s, where they
underwent standardized neuropsychological, functional and behavioral assessments as well as
neuroimaging. My study investigated potential differences in progression rates in different cognitive
domains, such as memory, language, and visuospatial function, in relation to treatment status. I also
investigated the sensitivity of behavioral measures to treatment effects as captured by the
Neuropsychiatric Inventory (NPI) and the potential differences in the activities of daily living using the
Disability Assessment for Dementia scores (DAD) Hypotheses: A) i) A slower rate of progression will be
seen overall in the treated group compared to the untreated group based on the Mattis Dementia Rating
scale, ii) some cognitive domains will be more responsive than others, specifically visuospatial/executive.
B) Improvement or less decline will be seen in the treated group in behavior as captured by the
Neuropsychiatric Inventory (NPI) and in function as measured by the Disability Assessment for Dementia
scale (DAD). Results: analysis is in progress right now. Conclusion: This study hopes to answer questions
concerning long term effects of a drug class, whose introduction to clinical use was based on 6-month
pivotal studies. This will help clinicians to better evaluate the ongoing utility of these drugs, and will also
help to understand their psychopharmacological effects.
13

5. Bercovici, Eduard 1,2 *, Cortez, M.A. 2 , Snead III, O. Carter 1,2
1. Institute of Medical Science, University of Toronto, Toronto, Canada; 2. Brain and Behaviour
Program, Division of Neurology, The Hospital for Sick Children Department of Pediatrics,
Faculty of Medicine, University of Toronto, Toronto, Canada
SEROTONIN DIRECTLY MODULATES AY-9944 INDUCED ATYPICAL ABSENCE
SEIZURES
Administration of the cholesterol inhibitor AY-9944 (AY) produces chronic atypical absence
seizures in Long Evans hooded rats. AY seizures are characterized as bilaterally synchronous 5-7
Hz slow spike and wave discharges (SSWD). In AY rats, SSWD are apparent during sleep, as are
myoclonic jerks. We hypothesized that serotonin can modulate AY induced SWD by acting on
the serotonin receptor subtypes 5-HT 2A and 5-HT 2C . The duration and frequency of SSWD that
characterize the AY model as well as SSWD duration were measured using electrocorticographic
(ECoG) recordings in freely moving animals. Using randomized counterbalanced dose response
design, rats were treated with either the 5-HT 2A agonist 1-[2,5-dimethoxy-4-iodophenyl]-2-
aminopropane (DOI, 0.5, 1 or 2 mg/kg), the 5-HT 2C preferring agonist m-chlorophenylpiperazine
(mCPP, 1, 2, or 4 mg/kg), or vehicle. DOI significantly reduced the total duration and number of
SSWD without affecting average burst duration. In contrast, mCPP had no effect on total duration
or number of SSWD, but significantly reduced the average burst at 1 and 2 mg/kg. These data
support the hypothesis that 5HT 2A receptors are involved in the pathogenesis of experimental
atypical absence seizures.
14

6. Bezchlibnyk, Yarema B. 1,2 , Young, L. Trevor 1,2 , Chen, Biao 2 , Wang, Jun-Feng 1,2 and
MacQueen, Glenda M. 2
1. Mood and Anxiety Program, Centre for Addiction and Mental Health, Department of
Psychiatry, University of Toronto, Toronto, Ontario; 2. Department of Psychiatry and
Behavioural Neuroscience, McMaster University, Hamilton, Ontario
CREB PHOSPHORYLATION IN THE AMYGDALA OF SUBJECTS WITH MOOD
DISORDERS
Signal transduction abnormalities have been identified in patients with bipolar disorder (BD) and
major depressive disorder (MDD). In addition, components of these signaling cascades have been
shown to be targets for mood stabilizers such as lithium, and antidepressant drugs. Since the
transcription factor cAMP regulatory element binding protein (CREB) is critical in converting
activity of signal transduction pathways to changes in cellular and molecular status, we measured
the level of phosphorylated CREB (pCREB) in postmortem amygdala sections consisting of
subjects with MDD, BD, schizophrenia and non-psychiatric, non-neurologic comparison
subjects (n = 15 per group). This region is critical for emotional processing, and important in the
pathophysiology of both BD and MDD. No significant differences were found between
diagnostic groups - non-psychiatric controls, subjects with BD, MDD, or schizophrenia (SCZ) -
but increased numbers of pCREB stained cells were identified in several amygdalar nuclei in
subjects who had died by suicide. In contrast, patients treated with lithium at the time of death
had significantly lower pCREB levels in the same region. These results may be important in
understanding the neurobiology of suicide and the well-documented anti-suicidal effect of
lithium.
15

7. Blech-Hermoni, Yotam*, Seltzer, Ze’ev
University of Toronto Centre for the Study of Pain, Faculty of Dentistry
A LOCUS ON CHROMOSOME 7 PLAYS A ROLE IN NEUROPATHIC PAIN IN HA AND
LA RATS AND IS ORTHOLOGOUS TO PUTATIVE PAIN QTL PAIN1 IN THE MOUSE
Background: Nerve injury produces in some humans chronic neuropathic pain. The same
variability is seen in animal models of chronic pain. In one model of chronic pain, a peripheral
nerve is transected. As a result, a neuroma develops at the site of injury and spontaneous firing
from this site, as well as from the cell bodies in the Dorsal Root Ganglia, begins shortly after.
Within a similar time-course, some animals begin to exhibit abnormal behaviour of licking,
biting, and scratching of the anesthetic foot. This abnormal behaviour is expressed
postoperatively over a period of weeks, can be quantified using an acceptable scale and is used as
a model of chronic pain. In previous studies, an outbred Sabra rat line was phenotypically isolated
into two distinct inbred lines: One expresses high levels of the abnormal behaviour (HA) and one
expresses no – or low – levels (LA). This phenotype was purported to be controlled by a single
autosomal recessive gene, although no speculation was made at the time with respect to its
possible identity (Devor & Raber, 1990). Subsequently, our group reported identifying a
Quantitative Trait Locus (QTL) on chromosome 15 of mice, having a major effect on this
phenotype. This QTL was named Pain1 (Seltzer et al., 2001).
Aims of investigation: To examine whether a rat genomic region orthologous to Pain1 in the
mouse plays a role in neuropathic pain in rats.
Methods: In this comparative study DNA samples were used from HA, LA, and Sabra rat lines.
15 microsatellite markers were chosen, to genotype a section of the 7q34 region of 45 HA, 37
LA, and 6 Sabra rats. This region is orthologous to the location of the Pain1 QTL on mouse
chromosome 15. An additional 6 markers were used to genotype other (control) regions on rat
chromosomes 3, 5, and 20.
Results: Six out of the 15 markers on chromosome 7 and 2 out of the 6 control markers were
informative, showing dimorphism in the tested DNA samples. Significant linkage disequilibrium
was found with these contrasting rat lines using the markers on chromosome 7, but not with the
control markers. Significant differences were found between HA and LA rats, using the Chi
Square test, examining the segregation of alleles of markers in the genotyped region of
chromosome 7, ranging from p

8. Bollig, Carmen M. 1 , Bressmann, Tim 1 , Uy, Catherine 1 , Thind, Parveen 1 , Irish, Jonathan C. 2
1 Graduate Department of Speech-Language Pathology, University of Toronto;
2 Department of Otolaryngology/Head and Neck Surgery, University Health Network, University
of Toronto
EVALUATION OF TONGUE SHAPES WITH 3-DIMENSIONAL ULTRASOUND IMAGING
IN GLOSSECTOMY PATIENTS PRE- AND POST-SURGICALLY
The aim of the present study is to assess tongue shapes and speech outcome in glossectomy
patients. Our data will enable us to investigate the quality of the surgical reconstruction technique
chosen for an individual patient. To this end, we use ultrasound imaging to compare pre-operative
and post-operative speech and tongue function in patients undergoing partial tongue resection
surgery.
The standard procedure for cancer of the tongue and adjacent structures is a partial glossectomy
and defect reconstruction. Our goal is to ascertain which reconstruction method provides the best
speech outcome and the most symmetrical tongue shapes for patients with different sites and sizes
of tumor lesions. The outcome of our study will enable us to provide valuable phonetic
information to oral surgeons in deciding which reconstruction method is most suitable for an
individual patient.
At this point we can present data of the first two patients, who were chosen for a comparison of
two methods of reconstruction. The one patient who suffered of a relatively small tumor (T1)
underwent a local defect closure and the other patient who had a severe in-cratered tumor (T3-4)
underwent a free gracilis flap reconstruction. The assessments, which were made with noninvasive
3-dimensional ultrasound imaging, took place shortly before and after the surgical
treatment, when the wound healing was completed. Using ultrasound we are able to investigate
the shape, position, surface and volume of the tongue in a novel way during the production of
speech sounds.
The perceptual evaluation of the post-operative speech of both subjects was close to normal
except for distortions mainly of alveolar consonants. Since ultrasound analysis allows for the
detection and visualization of compensatory tongue gestures in the production of speech sounds,
our data indicate that the tongue mobility of both subjects was decreased.
The 3-dimensional ultrasound volume reconstruction enabled us to undertake a detailed analysis
of the patients’ pre- and post-surgical tongue shapes. The ultrasound allowed us to validate that
the tongue reconstruction methods used for our two patients were adequate for the sites and sizes
of their tumors. The current paper offers a glimpse into the future perspectives our on-going
research.
The detailed quantitative analysis of tongue shapes and function using the ultrasound imaging will
allow us to establish scientifically based guidelines for the surgical reconstruction of tongue defects.
17

9. Caraiscos, Valerie B. 1 *, You-Ten, Kong E. 2 , Newell, J. Glen 3 , Elliott, Erin M. 1 , Rosahl,
Thomas W. 5 , Wafford, Keith A. 5 , MacDonald, John F. 3,4 and Orser, Beverley A. 1,2,3,6
1 Institute of Medical Science, Departments of 2 Anesthesia, 3 Physiology and 4 Pharmaceutical
Sciences, University of Toronto, Toronto, Ontario, Canada; 5 Merck Sharp & Dohme Research
Laboratories, Neuroscience Research Center, Terlings Park, Harlow, Essex, United Kingdom;
6 Department of Anesthesia, Sunnybrook & Women’s College Health Sciences Centre, Toronto,
Ontario, Canada
ANESTHETICS SELECTIVELY MODIFY A NOVEL FORM OF GABAERGIC INHIBITION
Background: Whole-cell recordings from hippocampal neurons show two distinct forms of
GABAergic inhibition: 1) transient synaptic transmission or miniature inhibitory post-synaptic
currents (mIPSCs) and 2) a persistent low-amplitude tonic current. Our lab has previously shown
that the tonic current in cultured hippocampal neurons is preferentially enhanced by the
intravenous anesthetic, propofol, compared to synaptic currents (Bai et al., 2001). We also
showed that extrasynaptic α5 subunit-containing γ-aminobutyric acid subtype A receptors
(α5GABA A Rs) generate a tonic current in hippocampal CA1 pyramidal neurons (Caraiscos et al.,
2004). Here, we test the hypothesis that the volatile (inhaled) anesthetic, isoflurane, differentially
enhances tonic versus synaptic currents by acting on α5GABA A Rs.
Methods: The whole-cell voltage-clamp technique was used to examine tonic and synaptic
GABAergic currents from wild type (WT) and GABA A R α5-/- cultured hippocampal neurons as
well as GABA-evoked currents from recombinant GABA A Rs expressed in HEK 293 cells. Cells
were voltage-clamped at a holding potential of –60 mV.
Results: We observed that the GABA A R α5 subunit was necessary for enhancement of the tonic
current by low concentrations (25 µM) of the volatile anesthetic, isoflurane, as potentiation was
absent in α5-/- neurons. At this concentration, isoflurane had no effect on mIPSCs recorded from
WT or α5-/- mice. Studies of recombinant human α5β3γ2L and α1β3γ2L GABA A Rs
demonstrated that the α5 subunit confers a marked sensitivity and efficacy to potentiation of
GABA-evoked currents by isoflurane.
Discussion: Our results show that low, amnestic concentrations of isoflurane selectively act on
tonic α5GABA A Rs in the hippocampus. The suppression of memory for traumatic surgical events
is an essential effect of anesthetics. These results suggest that extrasynaptic α5GABA A Rs are
primary targets for low concentrations of volatile anesthetics, thus providing the foundation for
investigating an association between tonic inhibition in the hippocampus and effects of
anesthetics on memory.
(Supported by the CIHR to VBC, JGN, JFM, BAO; the CAS to KEY-T; a Career Scientist Award
to BAO).
18

10. Cheung, Joyce & Wojtowicz, J. Martin
Department of Physiology, University of Toronto
AGE-RELATED CHANGES IN THE PRODUCTION AND MIGRATION OF NEW
NEURONS IN THE RAT OLFACTORY SYSTEM
The subventricular zone (SVZ) is one area in the mammalian brain where neurogenesis continues
into adulthood. Many of the cells generated in the SVZ are neuronal precursors that migrate
sagittally along a pathway known as the rostral migratory stream (RMS) to the olfactory bulb
(OB) where they differentiate into local interneurons. The goal of the present study was to
identify age-related changes in neurogenesis in the SVZ. Young (1-2 months old) and middleaged
(12 months old) rats were injected with bromodeoxyuridine (BrdU) to label dividing cells
that were subsequently quantified. The neuronal phenotype of the newly generated cells was
confirmed by double-labeling the cells with doublecortin (DCX), a marker of young migrating
neurons. It was found that in young rats, proliferation of new cells occurred in the SVZ and
migrated via the RMS to the OB within 10 days. Middle-aged rats exhibited cell proliferation in
the SVZ, RMS, and OB, but fewer of the newly divided cells differentiated into neurons. In both
groups of animals, there appeared to be a second population of cells within the SVZ that was
characterized by delayed proliferation and migration that occurred between 10 and 28 days. This
study demonstrates novel mechanisms in the production and migration of new neurons from the
SVZ via the RMS to the OB.
19

11. Chiu, Mary* & Orser, Beverley
Department of Physiology, University of Toronto
LOCALIZATION OF α5-CONTAINING GABA A RECEPTORS IN THE HIPPOCAMPUS
GABA A receptors (GABA A R) are hetero-pentameric ligand-gated chloride ion channels
composed of subunits from at least seven different classes (α1-6, β1-3, γ1-3, δ, ε, θ, π). Different
combinations of subunits confer diverse pharmacological and biophysical properties. α5-
containing GABA A R represents one of the minor combinations in the brain, as they constitute less
than 5% of the total GABA A receptor population. However, they are relatively highly expressed
(constituting approximately 20% of the GABA A R population) in the hippocampus, the part of the
brain that governs learning and memory. These α5-containing GABA A Rs have been shown to
mediate tonic GABAergic inhibition, a form of GABAergic conductance that arises from
activation of extrasynaptic receptors by low ambient concentrations of GABA in the extracellular
space (Caraiscos et al., 2004). This tonic conductance may provide a background level of
inhibition that regulates neuronal networks by mechanisms that are distinct from synaptic
transmission. Immunocytochemical study has also shown α5-containing GABA A Rs to have an
extrasynaptic localization (Brunig et al., 2002). In dissociated cultures of hippocampal neurons,
the α5 subunit was shown to have no apparent colocalization with gephyrin, a selective marker of
postsynaptic sites. There is also an almost complete lack of colocalization between α5 subunit
and PSD95 and Synapsin-I terminals, suggesting extrasynaptic localization of α5 GABA A R.
Given their relatively restricted expression in the brain and their potential physiological
importance, we seek to better understand these extrasynaptic α5-containing GABA A Rs.
Specifically, we propose to perform a subcellular fractionation protocol that allows us to
investigate the localization of hippocampal α5-containing GABA A Rs at a subcellular level. By
fractionating hippocampal neuron into its components, we may explore what other subunits
and/or proteins may associate with extrasynaptic receptors. This information offer fundamental
insights into the regulation of brain function and possible new strategies for developing target
specific therapeutic drug.
20

12. Cohn, Mélanie* 1 , Levine, Brian 1,2,3 , Black, Sandra E. 2,3,4 , Richards, Brian 5 , Kaufman,
Yakir 6 , Freedman, Morris 2,6 , and Moscovitch, Morris 1,3
Departments of 1 Psychology/ 2 Medicine (Neurology), University of Toronto; 3 Rotman Research
Institute at Baycrest Centre for Geriatric Care; 4 Sunnybrook and Women’s College Health
Sciences Centre; Departments of 5 Psychology/ 6 Behavioural Neurology, Baycrest Centre for
Geriatric Care, Toronto, Ontario
SEMANTIC AND EPISODIC MEMORY LOSS IN A CASE OF WHIPPLE’S
DISEASE ENCEPHALOPATHY
Background: Whipple's disease (WD) is a rare, chronic, multisystemic illness caused by the
bacteria Tropheryma whippelii. While symptoms are typically gastrointestinal, in rare cases the
central nervous system is affected. There are few descriptions of the cognitive symptoms
associated with WD, and only one of formal neuropsychological test results and none of
retrograde memory function.
Objectives: To investigate cognitive deficits, with an emphasis on episodic and semantic
retrograde memory function, in a case of WD encephalopathy presenting with an amnestic
syndrome, to relate these deficits to underlying brain abnormalities documented using MRI
technique, and to evaluate the findings in reference to current neuropsychological theories of
episodic and semantic.
Results: MS, a 49-year-old with WD encephalopathy, showed impaired visual spatial skills, smell
identification, speed of information processing, executive functions and anterograde memory
function on neuropsychological tests. In terms of retrograde memory, he showed impaired
autobiographical episodic memory for all life periods preceding the onset of his amnesia without
evidence of a temporal gradient. As for semantic memory, a temporal gradient of approximately
20 to 25 years was apparent in autobiographical and public knowledge domains. The pattern of
his episodic and semantic memory loss is consistent with MRI findings, which showed severe
atrophy in the medial temporal lobes bilaterally.
Conclusion: WD encephalopathy can result in a typical amnestic syndrome affecting both
semantic and episodic retrograde memory, but to different degrees, consistent with recent theories
regarding the role of the medial temporal lobe.
21

13. Cunic, D.I. 1,2 *, Paradiso, G. 1,2 , Kwan, C. 2 , Sailer, A. 1,2 , Moro, E. 1,2 , Poon, Y. 1,2 , Molnar, G. 1,2 ,
Gunraj, C. 1,2 , Lang, A.E. 1,2 , Lozano, A.M. 2, 3 , Chen, R. 1,2
1 Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada; 2 Toronto Western
Research Institute, Toronto, Ontario, Canada; 3 Division of Neurosurgery, Toronto Western
Research Institute, Toronto, Ontario, Canada
SOURCE GENERATORS OF EVOKED POTENTIALS FROM SUBTHALAMIC NUCLEUS
DEEP BRAIN STIMULATION
Purpose and Hypothesis: High frequency deep brain stimulation (DBS) of the subthalamic
nucleus (STN) alleviates the cardinal motor symptoms of advanced Parkinson’s Disease (PD), but
its mechanism of action remains unclear. Evoked potentials recorded from scalp electrodes have
been reported with STN DBS. However, their generator source and whether these potentials are
specific to stimulation of clinically effective contacts are not known. It is hypothesized that
generator sources of cortical potentials for clinically effective DBS will be similar in different
patients.
Methods: We studied 4 PD patients (mean age: 57 years; mean disease duration:15 years) with
bilateral STN DBS. All patients were on their usual medications. The clinical effectiveness of
the unilateral bipolar stimulation was verified by comparing UPDRS motor scores with the
stimulator turned off and on at the high frequency stimulation rate the patients normally use. To
record evoked potentials, high resolution EEG was recorded using a cap equipped with 58 scalp
electrodes and 6 inferior face electrodes. The STN was stimulated at 10 Hz with both the optimal
and other possible adjacent bipolar contact combinations (e.g. 0-1+, 1-2+, 2-3+, 2+3-) from the
implanted quadripolar stimulating electrode. Regional dipoles (source generators) of the
potentials evoked were calculated using Brain Electric Source Analysis (BESA) software, and
their location was estimated using an averaged brain.
Results: High frequency bipolar stimulation at the optimal contacts improved UPDRS motor
scores in all patients (mean improvement: 21%). In all patients, a potential with latency of about
20 ms was consistently observed with stimulation at optimal contacts. In 3 patients this potential
was positive (average peak latency:23ms; average amplitude:1.53μV) and was maximal over the
medial-posterior frontal leads. In one patient, the potential was negative (19ms;-0.59μV) and was
maximal over the parietal cortex. Regional dipole analysis localized the generator source of this
potential (average time of peak regional dipole source activity: 22ms) in all patients to the
ipsilateral medial premotor cortex . This regional source was not observed with stimulation of the
lowest contacts (0-1+).
Conclusions: STN stimulation at clinically effective contacts activates the ipsilateral premotor
cortex at a latency of about 22 ms. This suggests that STN DBS may work in part through
activation of the cortex.
22

14. Elliott, Erin M. 1 *, MacDonald, John F. 2,3 , and Orser Beverley A. 1,2,4,5
1 Institute of Medical Science, Depts. of 2 Physiology, 3 Pharmacology, 4 Anesthesia, Univ. of
Toronto, Toronto, ON, Canada, M5S 1A8; 5 Dept. of Anesthesia, Sunnybrook & Women’s College
HSC, Toronto, ON, Canada, M4N 3M5
TONIC BUT NOT SYNAPTIC INHIBITORY CONDUCTANCE IN MURINE HIPPOCAMPAL
NEURONS IS ENHANCED BY LOW CONCENTRATIONS OF THE β2/3 SUBUNIT
SELECTIVE ANESTHETIC ETOMIDATE
Hippocampal neurons are regulated by two types of inhibitory conductances including a rapid
phasic conductance generated by post-synaptic GABA A receptors (GABA A Rs) and a low
amplitude, persistent tonic conductance putatively mediated by extrasynaptic GABA A Rs. We first
reported that phasic and tonic conductances in the hippocampus are generated by
pharmacologically distinct populations of GABA A Rs. Gabazine (Mol Pharmacol 2001; 59:814)
and penicillin (Mol Pharmacol 2003; 63:2-8) selectively blocked the synaptic but not tonic
conductance in CA1 pyramidal neurons and neurons grown in primary culture. Here we report that
low concentrations of etomidate, an anesthetic that selectively modulates β2/3 subunit-containing
GABA A Rs, enhanced the tonic current but not phasic conductance. Whole cell currents (–60 mV)
were recorded from murine hippocampal neurons (E17) grown in dissociated cultures. Etomidate
(100nM) enhanced the amplitude of the tonic conductance by 91.8 ± 23.7 % (n=7, p1µM) further enhanced the
tonic conductance (229.1 ± 57.0 % at 1µM, n=10, p< 0.05). Additionally, concentrations above 1
µM also prolonged decay (τ w = 21.4 ± 3.7 vs 24.8 ± 2.9 msec; n=8, p

15. Fawcett, A.P. 1 *, Moro, E. 2 , Lang, A.E. 2 , Lozano, A.M. 3 , Hutchison, Wm.D. 1,3
1. Dept. of Physiology 2. Dept. of Medicine, Division of Neurology 3. Dept. of Surgery, Div. of
Neurosurgery, University of Toronto, Toronto, Ontario, Canada
PALLIDAL DEEP BRAIN STIMULATION (DBS) INFLUENCES BOTH REFLEXIVE AND
VOLUNTARY SACCADES IN HUNTINGTON’S DISEASE
Introduction: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is being
evaluated as a potential new therapy for patients with Huntington’s disease (HD). In addition to
the skeletal movement disorders, HD patients have oculomotor deficits, including difficulty
initiating voluntary saccades and difficulty in suppressing rapid saccades towards newly
appearing stimuli.
Purpose: This study measured changes in several saccade parameters, due to stimulation, in one
of the first HD patients to be implanted with bilateral GPi DBS in the world. The aim of this
study was to determine if oculomotor performance improved with stimulation in parallel with
clinical scores.
Methods: Oculomotor performance was assessed using three testing paradigms: prosaccades,
anti-saccades and memory-guided saccades. The data from the HD patient was also
compared to that of two healthy controls.
Results: Pallidal DBS decreased pro-saccade latency, total movement time and the number of
correctly executed trials, as well as increasing saccade gain compared to values when stimulation
was off (p

16. Giannoylis, Irene* 1 , Nelson, Aimee J. 3 , Staines, Richard W. 3,4 , McIlroy, William E. 2,3,4
1. Department of Physiology, University of Toronto; 2. Graduate Department of Rehabilitation
Science, University of Toronto; 3. Sunnybrook & Women’s College Health Science Center,
University of Toronto; 4. Kinesiology & Health Science, York University, Toronto, ON, Canada
EFFECTS OF PERCEIVED EFFORT DURING A MOTOR TASK MEASURED USING FMRI
Studies revealing brain changes associated with motor learning and recovery of motor function
following injury fail to account for the confounding effects of perceived effort on cortical
activation. Previous work on sense of effort has typically altered the sensorimotor demands of a
motor task by inducing muscle fatigue. We currently vary task difficulty without changing
peripheral motor state to reveal changes in the underlying neural network associated with
differences in perceived effort. We employed a motor task involving simultaneous abd/adduction
of the 3rd and 4th digits. The task was performed when: 1) digit pairs (2nd/3rd) and (4th/5th)
were taped (easy) and 2) when digit pairs were not taped (difficult). Twenty healthy young righthanded
subjects were imaged using a 1.5 T GE echospeed MRI while performing the task with
their dominant hand for 15 seconds interleaved with a 15 second rest condition for 10 epochs over
a 5 minute period. Subjects were recruited who rated the task (without assistance from tape) as
easy (n=10) or difficult (n=10). A 10-point rating scale for perceived effort was used to select
subjects and to measure effort following the performance of each task during scanning. Overall, a
greater sense of effort resulted in greater activation in primary, secondary, and association motor
cortices. Our findings have implications for studies reporting brain changes associated with
changes in motor function such as occur during stroke recovery or sensorimotor learning. This
work reveals the importance of developing experimental designs to control and/or monitor not
only the sensorimotor demands of a task but also the perceived effort.
(Support Contributed By: OHSF & CIHR)
25

17. Glazer, P. M.* 1 , Quant, S. 2 , Maki, B. E. 2, 5 , & McIlroy, W. E. 1,2,3,4
1 Graduate Department of Rehabilitation Science, 2 Institute of Medical Science, 3 Department of
Physical Therapy, 4 Toronto Rehab Institute, University of Toronto; 5 Centre for Studies in Aging,
Sunnybrook and Women’s College Health Sciences Centre, University of Toronto
THE EFFECT OF VERBAL FLUENCY TASK ON BALANCE CONTROL
The literature has well documented that the elderly are at an increased risk of falling and that this
risk is exacerbated by decline in cognitive functioning. Over the past several years the
relationship between cognitive status and postural stability has been extensively studied and
resulted in evidence for direct association between posture and cognition. Despite these efforts
the mechanism of cortical involvement in postural control still remains largely unknown. The
purpose of this study was to provide basic understanding of the association between specific
aspects of cognitive function and the control of stability, but more specifically to assess whether
cortical areas believed to be involved in attention switching are involved in the control of posture.
The novelty of this approach was to explore the influence on postural control of concurrent
performance of cognitive tasks that have well described underlying cortical networks. The
Verbal Fluency (FAS) task is a standard neuropsychological test involving activation of two
different areas of the cortex in two separate tests. One of the subtests, the Phonemic Fluency (PF),
assesses word generation and switching ability which is mediated by the frontal lobes, while the
Semantic Fluency (SF) counterpart is believed to involve a temporally mediated lexical search.
This dissociation between tests provides an opportunity to provide insight about localization of
specific cortical areas involved in cognitive control of postural stability as well as gaining
evidence for specific cognitive processes involved in postural control. Since the prefrontal cortex
is believed to be involved in attention switching it was hypothesized that postural control would
be disrupted when Phonemic Fluency but not Semantic Fluency is performed concurrently.
26

18. Guy, Allison* & Broussard, Dianne
Department of Physiology, University of Toronto, Canada
Toronto Western Research Institute, University of Toronto, Canada
INVESTIGATION OF THE ROLE OF IONOTROPIC GLUTAMATE RECEPTORS IN
SHORT-TERM PLASTICITY IN THE MEDIAL VESTIBULAR NUCLEI
Purpose. To investigate the role of ionotropic glutamate receptors in short-term plasticity at the
synapses between primary vestibular afferents and second order vestibular neurons in the medial
vestibular nuclei (MVN). Short-term plasticity at these synapses changes their strength, thus
altering the information processing characteristics of these neurons. These changes may cause
these neurons to act as frequency filters and may play a role in altering the vetibulo-ocular reflex
in response to immediate changes in the environment.
Methods. Using 600 mm coronal slices of mouse brainstem (P14-P32), we induced short-term
plasticity in second order vestibular neurons by stimulating vestibular afferents with bipolar
tungsten electrodes and currents of 20-100 mA. We were able to observe the effect of stimulation
by recording from second order vestibular neurons with an Axoclamp 2A amplifier. Using paired
pulses (IPI 5ms – 50 ms) and trains of various frequencies (10 Hz – 100 Hz) as stimuli, we were
able to investigate the dynamics of these synapses in the MVN.
Results. In three cells, we observed short-term facilitation at the synapses between primary
vestibular afferents and second order vestibular neurons. An analysis of the peak amplitudes of
the first and second peaks evoked by paired-pulse stimuli suggest that this phenomenon may be
post-synaptic in these three synapses.
Future Directions. We will continue to observe the synaptic dynamics between the primary
vestibular afferents and the second order vestibular neurons in the MVN. We will also be
applying ionotropic glutamate receptor antagonists, APV and NBQX, to observe the role of
AMPA receptors and NMDA receptors respectively in short-term plasticity at these synapses.
27

19. Ho, Stephanie K.Y. 1 *, Kovacevic, Natasha 2 , Chen, Josette X. 2 , Henkelman, Mark R. 2 ,
Henderson, Jeffrey T. 1
1
Department of Pharmaceutical Sciences, University of Toronto, 2 Mouse Imaging Centre,
Hospital for Sick Children, Toronto
ROLE OF EPHB RECEPTORS IN MURINE CNS AXON GUIDANCE
A crucial step in the proper assembly of mammalian central nervous system (CNS) is the
guidance of axons to their appropriate synaptic targets. With respect to this, Eph receptors have
been shown to play a key role in the formation of many neural structures. In order to gain a better
understanding of these receptors and their role in axon guidance, wild-type and Eph mutant brains
are analyzed by high-resolution MRI. A major advantage of high-resolution MRI over traditional
histological methods is that it provides an accurate three-dimensional (3D) representation of CNS
structures and allows analysis of morphological changes in a high throughput manner. As a first
step to validate high-resolution MRI as a tool for examining axonal tracts and to determine the
sensitivity of this system, Eph mutants previously shown to exhibit axon guidance defects in their
anterior commissures were examined. The results obtained for EphB2 using this system
compared favorably with those previously described using histology. At present, an extensive
analysis of the EphA4 null mutants has been performed and compared to EphB2. The results
demonstrated interesting similarities and differences between B2 and A4 mutants. Furthermore,
these findings support the concept that EphB-family members delineate distinct zones of axon
guidance cues.
28

20. Huang, Juan 1 , Wu, Xihong 1 , Yeomans, John 2 , Li, Liang 1,2
1 Department of Psychology, Speech and Hearing Research Center, Peking University, Beijing,
China, 100871
2 Department of Psychology, Centre for Research on Biological Communication Systems,
University of Toronto, Toronto, Ontario, Canada M5S 3G3
EFFECTS OF TETANIC STIMULATION OF THE AUDITORY THALAMUS OR
AUDITORY CORTEX ON ACOUSTIC STARTLE RESPONSES IN AWAKE RATS
The amygdala plays an important role in both emotional learning and fear potentiation of the
startle reflex. The lateral nucleus of the amygdala (LA), which receives auditory inputs from both
the auditory thalamus (medial geniculate nucleus, MGN) and the auditory association cortex
(AAC), is a critical structure for auditory fear conditioning. The central nucleus of the amygdala,
which has intra-amygdaloid connections with the LA, increases startle magnitude via midbrain
connections to the startle circuits. Although tetanic stimulation of either the MGN or the AAC in
vitro or in vivo can induce long-term potentiation (LTP) in the LA, the behavioral consequences
of tetanization of each of these two auditory afferents have not been reported. In the present
study, the startle reflex, elicited by either an intense noise or noise paired with transient electrical
stimulation of MGN or AAC in awake rats, was enhanced by tetanic stimulation of MGN, but
suppressed by that of AAC. The tetanization-induced changes of startle diminished within 24
hours. Transient electrical stimulation of the MGN, but not the AAC, either inhibited or enhanced
startle, depending on the interval between the electrical stimulus and startling stimulus.
Moreover, block of GABA B receptors in the LA reversed the effect of tetanic stimulation of the
AAC on startle but did not change the effect of tetanic stimulation of the MGN. The results
suggest that MGN and AAC afferents play a differential role in emotional modulation of startle.
The AAC inputs to the LA are more dependent on the inhibitory GABA B transmission.
29

21. Hwang, Rudi 1 *, Deluca, V. 1 , Masellis, M, 1 Mueller, D. 1 , Czobor, P. 2 , Volavka, J. 2 ,
Lieberman, J.A. 3 , Meltzer, H.Y. 4 , Kennedy, J.L. 1
1. Neurogenetics Section, Centre for Addiction and Mental Health (CAMH), University of
Toronto; 2. Nathan S. Kline Institute for Psychiatry Research; 3. University of North Carolina at
Chapel Hill; 4. Case Western Reserve University
INVESTIGATING THE EFFECT OF DOPAMINE D1 & D2 RECEPTOR GENE
POLYMORPHISMS ON ANTIPSYCHOTIC TREATMENT RESPONSE
Hypothesis: Based on evidence that dopamine D1 receptors play a role improving cognitive and
working memory deficits in schizophrenic patients and based on evidence that blockade of
dopamine D2 receptors is the primary mechanism by which symptoms of psychosis are
alleviated, we hypothesize that dopamine D1 and D2 receptor gene polymorphisms may play a
role in predicting antipsychotic treatment response.
Methods: Four single nucleotide polymorphisms (SNPs) in DRD1 and 11 SNPs spanning DRD2
were genotyped in three schizophrenic populations. These samples had a total number of about
280 patients. Treatment (clozapine, haloperidol, olanzapine, and risperidone) response data was
evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric
Rating Scale (BPRS). Analysis of covariance and X 2 were used to compare genotype group
differences in treatment response. Linkage disequilibrium analysis was used to reveal haplotype
blocks within the genes that was in turn used to perform haplotype analyses.
Results: DRD2 –241 A/G SNP was associated with cognitive symptom scores from the PANSS
in one sample as well as positive symptom scores from the BPRS in another sample. DRD2 –141
C Ins/Del polymorphism was associated with negative symptom subscale change scores in two
different samples as well as being associated with overall BPRS response when two samples were
combined. A trend was observed for DRD1 –48 A/G SNP in predicting negative symptom
change scores as well as overall improvement.
Conclusions: These exploratory results are interesting and suggest a possible role for DRD1 and
DRD2 genes in prediction of subtypes of response to antipsychotic treatment. Replication in
larger and independent samples is warranted.
30

22. Labrie, Viviane* 1,2,3 , Lipina, Tatiana 3 , Roder, John 1,2,3
1 Collaborative Program in Neuroscience, 2 Institute of Medical Science, 3 Samuel Lunenfeld
Research Institute, Mount Sinai Hospital, Toronto, Canada
THE BRAIN GLUTAMATERGIC SYSTEM AS A TARGET FOR NOVEL CLASS OF
NEUROLEPTICS
Schizophrenia is frequently characterized by disturbances in sensorimotor gating and in
attentional processes, which can be measured by pre-pulse inhibition (PPI) and latent inhibition
(LI), respectively. Researchers have implicated dysfunction of the glutamatergic system to be
involved in this disorder. Behaviours analogous to the symptoms of schizophrenia can be
mimicked in both humans and rodents by inhibiting NMDA receptor neurotransmission. The
pharmacologically-induced hypofunctional NMDA receptor model consequently provides a
means of assessing the efficacy of putative neuroleptics. This study examines whether drugs that
target the glutamate system; D-serine and ALX5407, have an effect on the PPI and LI of mice, in
the presence or absence of an NMDA receptor antagonist; MK-801. Inbred C57Bl/6J mice were
tested in a startle reactivity paradigm, following the administration of drugs. Latent inhibition
compared the response animals had to a tone, after having received 0 or 40 tone pre-expositions,
4 tone-shock associations, and systemic drug treatments. Thus the ability of D-serine and
ALX5407, to facilitate PPI, prevent disruption of latent inhibition, and reverse the effects of
NMDA receptor inhibition was determined. A comparison of these drugs with the effects of the
traditional atypical neuroleptic, clozapine, was equally completed to further identify their
suitability as potential neuroleptics.
31

23. Lau, A.*, Arundine, M., Tymianski, M.
Department of Physiology, University of Toronto, Toronto, Canada;
Division of Cellular and Molecular Biology, Toronto Western Research Institute, Toronto,
Canada
SIN-1 INDUCED NITRATION INHIBITS CASPASE-3 ACTIVITY IN THE
STAUROSPORINE MODEL OF CLASSICAL APOPTOSIS IN NEURONS
It has been shown that cells subjected to sublethal stretch followed by the application of an
otherwise tolerated NMDA treatment leads to increased neuronal death. This mortality exhibits
certain hallmarks of classical apoptosis, including irregular nuclear morphology and DNA
fragmentation. In addition, the presence of ROS, ONOO-, and other free radicals were readily
apparent in biochemical assays. However, these cells do not display an increased presence of
active caspase-3 protease, a main effector protein of the apoptotic pathway. It is our hypothesis
that the caspase-3 mediated pathway of cellular death is directly or indirectly inhibited by protein
nitration. Our studies employed the use of staurosporine, a known initiator of classical apoptotic
pathways; SIN-1, a nitration agent; or a combination of treatments. The stretch model was briefly
re-characterised and was consistent with previous data. Staurosporine (1uM) treated cells showed
increased active caspase-3 immunoreactivity starting at 3 h progressing to a least 24. Increased
cellular death was demonstrated by the larger proportion of propidium iodide stained cells,
though protein nitration was not observed. A titration curve of cell death versus SIN-1
concentration was also acquired. 1mM SIN-1 demonstrated sub-saturated levels of cell death
compared to treatments of 3mM SIN-1 and 10mM SIN-1. Cells subjected to 1mM SIN-1
displayed no active caspase-3 immunoreactivity from 3h to 24h, but showed increased protein
nitration beginning at 3h. Cotreatment of cells with 1uM staurosporine and 1mM SIN-1 or 3mM
SIN-1 displayed no immunoreactivity with a pan-caspase-3 antibody. However, cells cotreated in
this fashion still display increased cell death compared to controls. These results suggest that
some pathways of delayed neuronal death may be independent of caspase-3 activity and that
protein nitration is the key inhibitor.
32

24. Levy, Naama 1,2,3 *, Black, Sandra 1-5 , Caldwell, Curtis 1,2 , Lobaugh, Nancy 1,2,4 , Bocti,
Christian 1,4
Cognitive Neurology Unit and Imaging Research, Sunnybrook and Women's College Health
Sciences Centre 1 , Toronto, Ontario, Canada; Institute of Medical Science 2 , Program in
Neuroscience 3 , and Department of Medicine/Division of Neurology 4 , University of Toronto;
Rotman Research Institute and Baycrest Centre for Geriatric Care 5
IMPACT OF CEREBROVASCULAR COMORBIDITY ON SPECT PERFUSION IMAGING
AND EXECUTIVE FUNCTION IN ALZHEIMER'S DISEASE
An important issue confronting differential diagnosis in dementia and a major source of
heterogeneity is the frequent coexistence of Alzheimer's Disease (AD) and Cerebrovascular
Disease (CVD). Although CVD is rarely the sole cause of dementia, small subcortical strokes
increase the likelihood of expressing dementia in those with co-occurring AD pathology. Such
facts have been shifting our understanding of how AD and CVD pathologies interact in the
human brain. In the landmark NUN study, only 57% of elderly women meeting pathological
criteria for AD were demented, whereas 93% with small vessel infarcts and AD were demented,
suggesting synergistic effects of AD and subcortical CVD on cognition.
Functional brain imaging techniques, such as Positron Emission Tomography (PET) and single
photon emission computed tomography (SPECT), are currently used for examining deficits in
regional cerebral blood flow and metabolism in several neurologic diseases, including stroke and
dementia. Brain SPECT is usually less expensive and more widely available. Numerous studies
have compared SPECT in AD, normal controls and/or other dementias; however few have
concentrated primarily on the functional effects of subcortical CVD alone or in combination with
AD. Hypothesis: 1.Patients with mixed AD and subcortical CVD evident as hyperintensities on
MRI will show prefrontal perfusion deficits on SPECT. 2.Executive dysfunction will correlate
with prefrontal perfusion deficits on SPECT and will be more common in patients with AD
mixed with CVD. Methods: Subjects meeting NINCDS- ADRDA criteria for probable and
possible AD, and DSM-IV criteria for dementia were recruited from the Cognitive Neurology
Clinic and Stroke Unit at Sunnybrook and Women's College Health Sciences Centre. After a
careful review of patient history by two independent clinicians, patients are classified into
subgroups according to the degree of subcortical cerebrovascular disease on imaging and
presence of focal signs. 50 AD patients with and 50 AD patients without subcortical CVD who
have undergone standardized neurological assessment and who are matched for age, education,
sex, and Mini-Mental State Exam score have been selected. The neuropsychological battery
includes Mattis Dementia Rating Scale, Weschler Memory Scale - Visual Reproduction, Rey-
Osterrieth Complex Figure Test, Benton Line Orientation and Boston Naming Test. Executive
functions are assessed with phonemic fluency, Digit Span, Wisconsin Card Sorting Test, Trails A
& B, and select subcategories of the Mattis Dementia Rating Scale. Structural MRI and SPECT
perfusion imaging performed within 90 days of neuropsychological testing will also be analyzed.
SPECT studies were acquired using our Picker 3000, triple-headed gamma camera, with ECD as
the tracer. Reconstructions are performed using our in-house software for coregistration to a
standardized MRI-derived Region of Interest anatomical template. Lesion load is assessed using a
white matter hyperintensity rating scale in all subjects.
Conclusion: This investigation of brain perfusion and behavior correlations aims to increase
understanding of the cognitive profile and clinical course in mixed AD and subcortical CVD with
particular attention to the impact of CVD on frontal perfusion and executive deficits.
33

25. McDonald, Heather* & Wojtowicz, J. Martin
Department of Physiology, University of Toronto
AGE-RELATED DECREASE IN HIPPOCAMPAL NEUROGENESIS: POSSIBLE
IMPLICATIONS FOR COGNITIVE DECLINE DURING AGING
The hippocampal dentate gyrus is one of two adult brain regions to which neurons are added
throughout life. Neurogenesis, the process by which new neurons are added to the brain, occurs
in the dentate subgranular zone when neural progenitors give rise to new cells. Our goal was to
investigate age-related changes in neurogenesis in order to understand if and how the new cells
may relate to memory impairments seen in aging subjects. The production of new granule cells
persists in aged and even senescent animals, but the rate of production declines steadily over the
lifespan, becoming considerably reduced to less than 10% of young values by about one year, or
middle age. The present study represents a quantitative comparison of neurogenesis in young and
aged rats, taking into account the proliferation, survival, and differentiation of cells produced by a
population of labeled progenitors. Thirty-eight day and 12-month-old Sprague-Dawley rats were
injected with 5-bromo-2¡¦-deoxyuridine (BrdU), a thymidine analogue, in order to label cells
dividing in the dentate gyrus over a 24-hr. period, and to follow their fates. Examined at several
time points ranging from one day to two months following injection, aged rats showed a 90%
decrease in cell proliferation, but similar patterns of cell survival (indicated by BrdU labeling),
neuronal differentiation (indicated by doublecortin labeling), and maturation (indicated by CaBP
labeling) relative to young. These results indicate that hippocampal neurogenesis, although it
occurs on a drastically reduced scale relative to young levels, continues to proceed normally in
aged rats. Based on previous results in our laboratory we suggest that the extreme reduction in
neurogenesis could have profound consequences for memory loss in aging adults.
34

26. Miller, R.C.* 1,5 , McIlroy, W.E. 1,2,3,6 , Mikulis, D.J. 7 , Jurkiewicz, M.T.* 3,7 , Popovic, M.R. 4,5,6 ,
and Verrier, M.C. 1,2,3,6 .
1. Department of Rehabilitation Science, 2. Physical Therapy, 3. Physiology, 4. Institute of
Biomaterials and Biomedical Engineering, University of Toronto; 5. Rehabilitation Engineering
Laboratory, 6. Toronto Rehabilitation Institute: Lyndhurst Center; 7. Medical Imaging, Toronto
Western Hospital; Toronto, Ontario, Canada
NEUROMUSCULAR RESTORATIVE THERAPY (NRT)
PURPOSE: To determine the effect of NRT for individuals with cSCI. RELEVANCE: NRT uses
functional electrical stimulation (FES), muscle strengthening, goal orientated functional training
and stretching with the ultimate goal of increasing hand grasping abilities. Function, motor
control, and cortical activation will be examined before and after participation in NRT to evaluate
change. METHODS: A right handed male (age 46, C6-7 with a traumatic cSCI, 4 years post
injury). Assessments [Spinal Cord Independence Measure (SCIM), standard neurological
classification (ASIA), kinematic hand analysis (KHA), quadriplegic hand assessment tool (Q-
HAT), standard electromyography, and functional magnetic resonance imaging (fMRI)] were
conducted before and after NRT, which was delivered 3 X / week for 3 months. This is a single
case repeated measures design. RESULTS: FMRI data suggested greater cortical involvement
during right palmar grasp compared to normals. Pre NRT scores were: ASIA: motor - 19/50
right, 11/50 left; sensory: light touch - 23/56 right, 22/56 left and pinprick - 11/56 right, 17/56
left; SCIM 64/100; KHA wrist range of motion (ROM) of 48 degrees (right) and 2 degrees (left),
finger ROM: PIP of 2.6 degrees (right) and 1.5 degrees (left), MIP of 1.5 degrees (right) and 1
degrees (left); Q-HAT 22/45 (right) and 12/45 (left). Post NRT scores will be reported.
CONCLUSIONS: A five point increase in the Q-HAT score would be considered significant, (i.e.
improved grasp performance) and should translate into an increase in force of 1.5 lbs/sq” for
palmar grasp and 0.5 kg for pinch grasp, with a concurrent improvement in range of motion.
35

27. Moore, Kathryn J. 1,2 & Shoichet, Molly S. 1,2,3
Department of Chemical Engineering and Applied Chemistry 1 ; Institute of Biomaterials and
Bioengineering 2 ; Department of Chemistry 3
COMBINED GRADIENTS OF NEUROTROPHIC FACTORS WORK IN SYNERGY TO
GUIDE NEURITE OUTGROWTH
Spinal cord injury is a devastating disorder. Early intervention with medicine prevents some
secondary damage after injury, and physical therapy provides some relief for patients, but a cure
likely requires regeneration of damaged axons in the spinal cord. Our research is focused on the
development of a device capable of bridging the gap in an injured spinal cord and encouraging
axons to regenerate within this device using peptides, drugs, and neurotrophic factors.
Neurons extend neurites in response to growth factors such as nerve growth factor (NGF) and
neurotrophin-3 (NT-3). Even more interesting is the fact that neurons, such as dorsal root ganglia
(DRGs) and pheochromocytoma (PC12) cells, extend neurites up an NGF concentration gradient
with a minimum gradient required for guidance. Our lab has demonstrated that DRGs and PC12
cells grow neurites in the direction of an immobilized gradient of neurotrophins. 1 In an attempt to
translate this fundamental research towards a device for clinical evaluation, our current research
goals are to create a cell-adhesive, cell-invasive polymer scaffold to entrap NGF and NT-3
together in combined immobilized concentration gradients, and to look for synergism in the
guidance of neurite extension along these combined gradients.
NGF and NT-3 act on the cell through two tyrosine kinase receptors, TrkA and Trk C,
respectively. These two receptors initiate neuronal responses through different signaling
cascades 2 , thus allowing possible interactions between the cascades, resulting in synergistic
responses. But for interactions to occur, the two receptors must be located on a single cell. We
were able to show the presence of both receptors on E10 chick DRG cells through double
immunolabelling.
Crosslinked p(HEMA) scaffolds are cell-invasive at 15 wt%, and have been shown both to entrap
NGF and NT-3 and maintain stable concentration gradients of these neurotrophins. Using this
system, effective guidance of DRG neurites was achieved with a NGF concentration gradient of
310 ng/ml/mm alone. When combined NGF and NT-3 gradients of only 200 ng/ml/mm each were
used, guidance was also observed; however, gradients of either NGF or NT-3 alone at 200
ng/ml/mm were unable to guide neurites and served as controls. Gradients of one neurotrophin at
200 ng/ml/mm with the second neurotrophin at a homogeneous concentration were also unable to
guide neurite growth. This suggests that the mere presence of the second growth factor is
insufficient to achieve synergism - the second neurotrophin gradient is required.
We plan to test the efficacy of these gradient scaffolds in vivo to enhance regeneration following
injury to the spinal cord.
Acknowledgments: We are grateful to NSERC for funding.
1. Kapur T, Shoichet MS. Immobilizing a concentration gradient for neurite guidance.
Submitted to Journal of Biomedical Engineering, September 2002.
2. Song HJ, Poo M. Signal transduction underlying growth cone guidance by diffusible
factors. Current Opinion Neurobiology 9: 355-363, 1999.
36

28. Niechwiej-Szwedo, E.* 1 , Gonzalez, E. 2,3,4 , Steinbach, M.J. 1,2,3,4
1 Institute of Medical Science, 2 Department of Ophthalmology and Vision Science, University of
Toronto; 3 Vision Science Research Program, Toronto Western Hospital; 4 Centre for Vision
Research, York University
LOCALIZATION OF TARGETS IN DEPTH WITH ALTERED AFFERENT FEEDBACK
Knowledge of eye position is important for the perception of visual direction and to maintain
space constancy during eye movements. The central nervous system (CNS) can obtain non-visual
information about eye position from two sources: outflow (efferent copy of the motor command)
and inflow (afferent feedback from the eye muscles). Palisade Endings (PE), which are associated
with the global layer of the eye muscles, might provide the proprioceptive information about eye
position. Recent evidence suggests that the PE are innervated by a distinct set of non-twitch
motor neurons found in the periphery of the oculomotor nuclei that control eye movements.
Moreover, activity in the non-twitch motor neurons does not add to the force used to move the
eye. It has been hypothesized that these non-twitch motor neurons could be involved in
modulating the gain of sensory feedback, analogous to the gamma-efferent fibers which control
the sensitivity of muscle spindles in the skeletal muscles. The purpose of this study was to
examine the above hypothesis using behavioral methods. Specifically, it was hypothesized that
altering the gain of the afferent feedback from eye muscles would result in misregistration of eye
position and increased pointing errors with the arm. The Jendrassik maneuver (JM) was used to
alter the afferent feedback by increasing the efferent activity of the non-twitch fibers that
innervate the PE.
Healthy, young adults (n=8) were seated in total darkness and were asked to look and point to
green lights which appeared at two distances in depth (25 and 45 cm). Eye movement data were
collected using the El-Mar eye tracking system, and pointing responses were measured with an
electromagnetic tracking device (Flock of Birds). Participants were tested in 3 experimental
conditions, which were randomized as to order: 1. control (look and point to target); 2. look and
point during JM (while performing a muscle contraction with the lower limbs); 3. look during JM
and point after JM (point 2-3 sec after the contraction has been released). Data were analyzed
using a custom software program and focused on the end-point accuracy of vergence eye
movements and hand movements.
Results: Subjects systematically overshot the target with the hand, and converged beyond the
target in all the conditions. Pointing responses were significantly less accurate (p

29. Rivkin, Elena* & Cordes, Sabine
Department of Molecular and Medical Genetics
FORWARD GENETIC RECESSIVE SCREEN TO IDENTIFY NOVEL MOUSE MUTANTS
WITH DEFECTS IN HINDBRAIN PATTERNING
Cranial nerves arise in a highly stereotypical manner in the embryonic hindbrain, and serve as
landmarks for proper hindbrain development. The genetic hierarchy that governs specification
and patterning of each individual cranial nerve is still largely unknown. To identify novel mouse
mutations that affect cranial nerve development we performed a small-scale, recessive
mutagenesis screen using the chemical mutagen N-ethyl-N-nitrosourea (ENU). As a phenotypical
assay for mutant selection we performed immunohistochemical analysis using the 2H3 antineurofilament
antibody. In total, the progeny of 41 carrier males were analyzed. From these, 6
had axon guidance defects, and 2 had ventral patterning defects.
In one of the mutants, which we named gumby, anti-neurofilament staining of 10.5dpc revealed
an abnormally sprouting facial nerve (cranial nerve VII). At embryonic days 11.5-12.5dpc, gumby
homozygotes had severely reduced lower jaws (micrognathia), abnormally shaped heads, and
lacked blood. The gumby mutation is embryonically lethal at day 13.5dpc.
To localize the locus affected by the gumby mutation we used meiotic backcrosses that segregate
the phenotype relative to known molecular markers. Interestingly, gumby is located in a region
that is syntenic to a region of human chromosome that has been implicated in Cri du Chat
Syndrome (CDCS). CDCS is one of the most common deletion disorders with an incidence of 1
in 20,000 live births. Hallmarks of this syndrome include severe mental retardation, speech delay,
hypotonia, microcephaly, hypertelorism, epicanthal folds, micrognathia, and a high-pitched cry
similar to the mewing of a cat. Therefore, our future analysis of gumby may provide biologic
understanding of some of the clinical features of Cri Du Chat syndrome.
Our results demonstrate the productivity of small-scale mutagenesis screens for identifying novel
neurodevelopmental mouse mutations. Clearly, some novel mutations such as gumby, not only
can provide insight into vertebrate neurodevelopment, but also allow us to model aspects of
human neurodevelopmental disorders.
38

30. Saab, Béchara 1,2 *, Georgiou, John 2 , Roder, John 1,2
1 Collaborative Program in Neuroscience, Molecular & Medical Genetics Department, University
of Toronto, 2 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
THE C-TERMINAL PEPTIDE OF THE CALCIUM SENSOR, NCS-1, MODULATES SHORT-
TERM SYNAPTIC PLASTICITY IN THE MOUSE HIPPOCAMPUS
Synaptic plasticity, including learning and memory, is thought to be regulated by changes in
calcium concentrations at nerve terminals. Calcium influx into both the pre- and post-synapse
triggers a cascade of events to alter their physiology. These calcium-dependent cascades are
likely mediated by certain proteins of the calcium-binding protein (CBP) superfamily (of which
calmodulin is the best understood). The most sensitive CBP, the intriguing protein neuronal
calcium sensor-1 (NCS-1), is believed to have a prominent role in synaptic plasticity and underlie
the thought processes that lead to learning and memory. Here we shown that the C-terminal
peptide of NCS-1 fused to the HIV-1 protein transduction domain (TAT) sequence modulates
short-term synaptic plasticity. Paired pulse facilitation (PPF) and post-tetanic potentiation (PTP)
are increased in the CA1 and dentate gyrus hippocampal regions of slices. These data suggest
that mice containing the C-terminal NCS-1 peptide will have altered thought paradigms leading
to behavioural differences from wild-type mice.
39

31. Seminowicz, D.A.*, Mikulis, D.J., Davis, K.D.
Institute of Medical Science
CORTICAL NOCICEPTIVE ACTIVITY IS ALTERED DURING COGNITIVE
ENGAGEMENT
Interactions of pain and cognition have been studied in humans and animals previously, but a
clear relationship of behavior and brain activity has not previously been shown. We aimed to
show using functional MRI how a cognitively demanding task (Stroop) modulates pain-related
brain activations and conversely, how pain modulates attention-related activity. Reaction time
(RT) data indicated two types of pain responders: subjects in the A group had a faster Stroop
reaction time when pain was concomitant to the task, while those in the P group had a slower
Stroop performance during painful stimulation. Two region of interest analyses were performed.
We first tested whether brain areas activated during painful median nerve stimulation were
modulated by cognitive load. We next tested whether brain areas activated during the high
conflict cognitive task were modulated by pain. Pain-related activity in three regions, primary
(S1), and secondary (S2) somatosensory cortices, and anterior insula, was attenuated by cognitive
engagement, but this effect was specific to the A group. Pain-related activity in the caudal and
rostral anterior cingulate cortex (ACC) and ventroposterior thalamus were not modulated by
cognitive load. None of the attention-related areas, including bilateral dorsolateral prefrontal and
posterior parietal cortices, were modulated by pain, although a nonsignificant trend was noted.
These findings suggest that pain networks can be modulated by cognitive strategies.
Furthermore, the distinction of behavioral subgroups may relate to cognitive coping strategies
taken by patients with chronic pain.
40

32. Setnik, Beatrice 1,2 * & Nobrega, José N. 1,2
1
Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, ON,
Canada; 2 Department of Pharmacology, University of Toronto, Toronto, ON, Canada
SEX-DEPENDENT UPREGULATION OF CORTICAL TrkB RECEPTOR mRNA LEVELS IN
THE LEARNED HELPLESSNESS MODEL OF DEPRESSION
Neurotrophic factors have been recently recognized for their role in behavioural and plasticityrelated
alterations in patients with major depression. The biological activity of neurotrophic
factors such as brain-derived neurotrophic factor (BDNF), which itself has been shown to exert
antidepressant effects, are largely mediated by the receptor tyrosine kinase-B (TrkB). Since
BDNF levels are decreased in animals exposed to both acute and chronic stress, this may
potentially affect levels of the TrkB receptor in stress-dependent animal models of depression.
Furthermore, BDNF levels fluctuate in response to hormonal changes in females. The learned
helplessness animal model of depression was used in this study to determine how Trk B levels are
affected according to depressive behaviour and sex. Male and female rats, in diestrus, were
exposed to the learned helplessness paradigm and were classified as either learned helpless or
non-learned helpless on the basis of escape performance. Quantitative in situ hybridization
analysis was used to determine TrkB receptor mRNA levels in the frontal cortical regions of LH,
nLH and normal control rats. In males, TrkB receptor mRNA expression was consistently higher
in the LH group compared to control and nLH males in all 48 regions sampled, indicating an
association with learned helplessness behavior. This upregulation was most prominent in specific
regions including the primary somatosensory area (layer 4, +29.5%) and caudate putamen
(+24.5%). Females in the diestrus phase showed a pattern of TrkB upregulation distinct to that
of males. TrkB levels in females showed a trend towards upregulation in 81% of regions
sampled. This upregulation was observed in both groups exposed to stress, LH and nLH
collectively, relative to controls, reaching significance in 9 regions. Unlike males, females
showed a generalized stress effect as opposed to a behavioural effect, despite the fact that there
were no gender differences in vulnerability towards developing helplessness behaviour. These
results suggest that TrkB may play a role in both stress and learned helpless behaviour, however
these roles may be sex-dependent.
41

33. Shao, Li, Sun, Xiujun, Xu, Li, Young, L.Trevor and Wang, Junfeng
Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto,
Ontario, Canada
ENDOPLASMIC RETICULUM STRESS PROTEINS: A TARGET IN COMMON FOR MOOD
STABILIZERS LITHIUM AND VALPROATE IN NEURONAL CELLS
Lithium and valproate are highly effective treatments for bipolar disorder. Previous studies in our
laboratory found that chronic treatment with valproate increased the expression of endoplasmic
reticulum (ER) stress proteins GRP78, GRP94 and calreticulin in rat brain and C6 glioma cells.
We report here that in primary cultured rat cerebral cortical cells, expression of GRP78, GRP94
and calreticulin are increased by chronic treatment with lithium and valproate at therapeutically
relevant concentrations, but not increased by the other mood stabilizing drugs carbamazepine and
lamotrigine. Both mRNA and protein levels are increased by lithium and valproate. In contrast to
inhibitor of the ER Ca 2+ -ATPases thapsigagin, a classic GRP78 inducer, chronic treatment with
lithium and valproate has no effects on cell damage, intracellular free Ca 2+ concentration or
GRP78 translocation. Our results suggest that lithium and valproate increase the expression of
GRP78, GRP94 and calreticulin in primary cultured rat cerebral cortical cells without causing cell
stress. This also suggests that the mechanism of GRP78 increase induced by lithium and
valproate may be different from that of thapsigagin.
42

34. Sibley, K.M.* 1, 3 , Tang, A. 1-3 , Brooks, D. 1-3 , McIlroy, W.E. 1-3
1. Graduate Department of Rehabilitation Science, 2. Department of Physical Therapy, University
of Toronto, 3. Toronto Rehabilitation Institute, Toronto, Ontario
NEUROMUSCULAR AND CARDIOVASCULAR RESPONSES TO NOVEL PEDALING
STRATEGIES IN HEALTHY PARTICIPANTS
Recumbent seated pedaling has been proposed as a safe and effective form of neuromuscular and
cardiovascular rehabilitation following stroke. Studies of pedaling in people following a stroke
have shown that during pedaling the paretic limb performs significantly less work than the nonparetic
limb, which is compensating for weakness on the paretic side.
Traditional models of seated bicycle pedaling use a linked-crank paradigm in which the pedals
are mechanically coupled to one another. The mechanical constraints of the system are such that
the pedals do not move independently, and accordingly when one pedal is pushed down during
the extensor phase of the pedaling motion, the other pedal is rotated to the top of the cycle
without any active contribution by the flexing leg. The result is that traditional seated pedaling is
primarily extensor in nature with little active flexion. Patients with hemiparesis are able to
successfully pedal in spite of asymmetries in sensori-motor control because of the bicycle design.
While traditional recumbent bicycle pedaling is a good choice for cardiovascular training
following stroke, it does not optimally challenge the neuromuscular control pathways. To
maximize recovery, an ideal training program must ensure that both legs contribute to the
movement while maintaining the cardiovascular challenge. The purpose of this study was to
investigate the neuromuscular and cardiovascular characteristics of three novel pedaling
paradigms in young healthy participants for potential application to stroke rehabilitation.
Ten healthy males and females (mean age 28.7 +/- 1.1 years) were recruited for the study. All
participants performed a maximal exercise test to determine the maximum workload achievable,
which was used to determine exercise intensity for the study. A minimum of one week following
the maximal exercise test, participants returned to pedal in three novel pedaling paradigms (single
leg, visual feedback, spring-loaded Cyclocentric TM ) as well as traditional pedaling, which was the
control condition. All participants performed all four conditions, pedaling for four minutes in
each condition at 50% of the maximum workload achieved and at 70 revolutions per minute (25%
of maximum workload for the single leg condition). Participants were given five minutes of rest
in between conditions. Traditional pedaling was always performed twice: at the beginning and
end of testing, while the order of the three novel paradigms was counterbalanced between
participants. Sub-maximal oxygen uptake and surface electromyography of eight leg muscles
were recorded in each condition.
Preliminary analysis indicates that there were task-specific differences in the timing and
amplitude of muscle activation profiles and oxygen uptake characteristics. Ongoing work will
continue to examine cardiovascular and underlying sensori-motor control characteristics of novel
pedaling strategies in stroke patients with the goal of developing an optimized training program
for stroke rehabilitation.
43

35. Stevens, W. Dale 1 *, Cron, Greg O. 2 , Pappas, Bruce A. 3 , Santyr, Giles E. 2 , Grady, Cheryl L. 1
1. Rotman Research Institute, University of Toronto, Toronto, ON; 2. Department of Physics,
Carleton University, Ottawa, ON; 3. Institute of Neuroscience, Carleton University, Ottawa, ON
QUANTIFICATION OF CEREBRAL, RETINAL, AND VERTEBRAL BLOOD FLOW IN
RAT MODELS OF ISCHEMIA: A MRI STUDY
A model for inducing acute global ischemia has been introduced recently wherein bilateral
carotid artery occlusion (2VO) is combined with systemic hypotension (H2VO). Blood pressure
is reduced and maintained below 50 mm Hg by controlled anaesthesia via a respirator. This
model offers improvements as it has an extremely low mortality rate, yields consistent neural
degeneration and the ischemia is completely reversible. In both 2VO and H2VO models, the
extent to which the vertebral arteries compensate for reduced cerebral blood flow (BF), as well as
the time course and means by which this occurs, are not well known. Further, the extent of retinal
ischemia, a cause of ocular pathology in these models, is unknown. We used quantitative
dynamic contrast-enhanced magnetic resonance imaging (MRI) to quantify changes in cerebral
BF, vertebral artery BF, and retinal BF in adult male rats (N=10) during both 2VO and H2VO.
Each rat was anaesthetised with halothane, then imaged during a control condition, immediately
following 2VO, and in an H2VO condition respectively. An immediate and substantial increase in
vertebral BF occurred after 2VO, which was positively correlated with retinal BF. BF reduction
occurred in the retina, frontal cortex, temporal cortex, cerebellum, and midbrain, from most to
least respectively. These results indicate that anterior cerebral regions and the retina are
particularly vulnerable to ischemia in these models. As well, they indicate an immediate
compensatory increase in vertebral BF when the carotid arteries are occluded. Variability of
compensatory vertebral BF between rats may explain divergent effects of 2VO across studies
using different strains of rats.
Support Contributed By: CIHR and Ontario Heart and Stroke
44

36. Vessal, Mani* 1,2,3,4 , Dugani, Chandrasagar B. 4 , Solomon, Dianand A. 4 , Burnham, W.
McIntyre 1,2,3,5 , Ivy, Gwen O 4 .
Institute of Medical Science 1 , Program in Neuroscience 2 , and Bloorview Epilepsy Research
Program 3 , University of Toronto, Toronto; Centre for the Neurobiology of Stress 4 , University of
Toronto at Scarborough, Scarborough; Department of Pharmacology 5
GLIOGENESIS IN THE PIRIFORM CORTEX OF KINDLED SUBJECTS: A
QUANTITATIVE ANALYSIS OF FULLY KINDLED BRAINS
Complex partial epilepsy is a seizure disorder in which attacks frequently arise from foci located
in the temporal lobes. The amygdala-kindling model is a widely used model of complex partial
epilepsy with secondary generalization. This model is thought to mimic such seizures because
brain regions such as piriform cortex (PC), amygdala, and hippocampus, which are in the human
temporal lobes, are among brain regions that are the most prone to the development and
maintenance of the seizure-prone state. This study was designed to quantitatively assess
astrocytic proliferation in the rat-PC in the amygdala-kindling model of epilepsy in an attempt to
understand the functional significance of astrocytes in the maintenance of the epileptic state.
Five groups of male Wistar rats (n = 6 per group) were kindled to five stage 5 seizures. The
kindled subjects and their corresponding sham-kindled controls (n = 6 per group) were then
sacrificed after different survival periods: 1,7,18,30 or 90 days. Dividing astrocytes were
identified by double labeling with bromodeoxyuridine (BrdU) and either glial fibrillary acidic
protein (GFAP; expressed in mature astrocytes) or vimentin (Vim; expressed in immature
astrocytes) and quantified using a confocal laser-scanning microscope.
In addition to observing a significantly higher number of dividing astrocytes in kindled animals,
we also noted differences in the numbers of dividing astrocytes in the ipsilateral versus
contralateral-PC. Using one-way analysis of variance (ANOVA), we observed the highest
number of proliferating astrocytes in the 18-day group and the lowest in the 90-day post-kindled
group. Previous studies have demonstrated a significant role played by astrocytes in proper
synaptic functioning. Thus, the increased number of astrocytes may be involved in synaptic
reorganization and synaptogenesis, both of which have been observed in kindling. Furthermore,
the differences observed among the kindled groups, as well as between the PCs in both
hemispheres, may be suggestive of possible function(s) of astrocytes in facilitating neural
networks necessary in maintaining the seizure prone state.
45

37. Xu J.*, Xue S., Lei G., Kwan C.L., Yu X.-M.
Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
THE ROLE OF C-TERMINAL SRC KINASE (CSK) IN THE REGULATION OF NMDA
RECEPTORS
The regulation of N-methyl-D-aspartate (NMDA) receptors by Src family protein tyrosine
kinases has been implicated in a wide spectrum of physiological and pathological conditions in
the central nervous system (CNS), such as learning and memory, epilepsy, chronic pain and
neurodegenerative disorders. However, how Src kinase activity per se is regulated in the control
of NMDA receptors is still an open question. Recently, we have demonstrated that protein
tyrosine phosphatase alpha (PTPá), the activator of Src kinases, is necessary for the initiation and
maintenance of the up-regulation of NMDA receptors by Src kinases (The EMBO J. 2002, 21,
2977-2989). Furthermore, we found that the Src kinase inhibitor, C-terminal Src kinase (Csk)
may also complex with NMDA receptors in the brain. Specifically, Csk was found to associate
with co-expressed NMDA NR2A subunits in heterologous cells, and the Csk-NR2A association
could be enhanced by co-expression of constitutively active form of Src, but not the kinase dead
form of Src, indicating that the Csk-NR2A subunit interaction may be regulated by Src kinase.
Moreover, intracellular application of Csk (2nM) significantly inhibited the whole-cell currents
mediated by either native NMDA receptors in cultured hippocampual neurons or recombinant
NMDA (NR1-1a/NR2A) receptors in fibroblasts. In contrast, boiled Csk applied into cells had no
such effect, suggesting that Csk may down-regulate NMDA receptor activity. Taken together, it
was demonstrated that Csk, along with PTPá, may play important roles in finely regulating
NMDA receptor function in the CNS.
46

38. Zai, Gwyneth* 1,2 , King, Nicole 2 , Burroughs, Eliza 4 , Barr, Cathy L. 1,3,5 , Kennedy, James L.
1,2,3,5 , Richter, Peggy 3,4
1 Institute of Medical Science, University of Toronto; 2 Neurogenetics Section, Centre for
Addiction and Mental Health; 3 Department of Psychiatry, University of Toronto; 4 Anxiety
Disorders Clinic, Centre for Addiction and Mental Health; 5 The Toronto Hospital – Western
Division, Department of Psychiatry, University of Toronto
QUANTITATIVE TRAIT ANALYSIS OF THE GAMMA-AMINOBUTYRIC ACID BETA
RECEPTOR 1 GENE IN OBSESSIVE-COMPULSIVE DISORDER
Background: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric illness. Genetic
factors are believed to be important etiologically. Although genetic testing has focused on the
serotonergic and dopaminergic systems, there is increasing evidence that the major inhibitory
neurotransmitter, gamma-aminobutyric acid (GABA), may also be functionally involved.
Furthermore the GABA beta receptor 1 (GABBR1) gene has been localized to chromosome
6p21.3 region, which has shown linkage to OCD.
Purpose/Hypothesis: We hypothesize that variations within the GABBR1 gene might be a risk
factor for developing OCD. Methods: We investigated five polymorphisms (–7265A/G
substitution; 10497C/G substitution; 33795A/G substitution in the 3’-UTR; Ser491Ser-1473T→C
transition; Phe659Phe-1977T→C transition) in the GABBR1 gene in a sample of 159 DSM-IV
OCD probands and their families, using the transmission disequilibrium test.
Results: A trend was observed with an over-transmission of allele 1 at the A-7265G
polymorphism and OCD (χ 2 =3.270, P=0.071). Moreover, the TDT haplotype analysis using
TRANSMIT showed a trend toward association with the haplotype of the five polymorphisms
together [2.1.1.2.1 (A-7265G.C10-71G.Ser-491-Ser.Phe-659-Phe.A33795G)] with a chi-square
value of 3.418, which corresponds to a p-value of 0.065 (overall χ 2 =6.353, 5 d.f., P=0.273).
Moreover, a trend was observed for the total Yale-Brown obsessive-compulsive scale score in the
Phe-659-Phe polymorphism (z=1.934, P=0.053) using the family-based association test,
considering the diagnosis of OCD and then the clinically relevant quantitative phenotypes.
Conclusion: The observed trends suggest that further investigations of the role of the GABBR1
gene in OCD are warranted.
47

39. Zhao, Xiao-Han* 1,2 , Xin, Wen-Kuan 1,2 , Xu, Jindong 1,2 , Kwan, Chun L. 1,2 , Zhu,
Kang-Min 1,2 , Cho, Jae-Sung 1,2 , Duff, Missy 1,2 , Ellen, Richard P. 1,3 , McCulloch, Christopher
A.G. 1,3 and Yu, Xian-Min 1,2
1. Faculty of Dentistry, 2. Centre for Addiction and Mental Health, 3. The CIHR Group in Matrix
Dynamics, University of Toronto, Toronto, ON, Canada
CRITICAL CONTROL POINT: RECRUITING N-METHYL-D-ASPARTATE (NMDA)
RECEPTOR-MEDIATED TOXICITY
INTRODUCTION: Although NMDA receptor antagonists have shown clear benefit in protecting
neurons in experimental stroke/trauma models, clinical treatment of stroke/trauma patients with
NMDA receptor antagonists has not yielded promising results.
OBJECTIVES: The purpose of this project was to characterize mechanisms of how NMDA
receptor activity is recruited to cause toxicity in the central nervous system (CNS).
METHODS: Cultured hypocampal neurons were prepared from E15-E19 rat embryos. Neuronal
Image, NMDA single channel activity and [Na + ] i and [Ca 2+ ] i were recorded at 10-14 days after
plating. Neuronal images were immediately (

UNDERGRADUATE POSTER ABSTRACTS
40. Capano, Lucia
Undergraduate Neuroscience Specialist Program
INVESTIGATION OF DNA VARIANTS IN THE 5’-REGULATORY REGION OF THE
DRD1 GENE IN ATTENTION DEFICIT/HYPERACTIVITY DISORDER
Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent childhood psychiatric disorder
with a strong genetic basis. The Dopamine receptor D1 gene (DRD1) is a strong candidate for
involvement in ADHD. A recent linkage study by Misener et al. (2003) tested for linkage of
DRD1 to ADHD and in that study the Transmission/Disequilibrium Test (TDT) showed biased
transmission of a particular DRD1 haplotype, designated Haplotype 3. This finding supports the
hypothesis that the DRDI gene is involved in this disorder, and implicates Haplotype 3 in
particular, as a risk factor. However, the polymorphic markers used in that study were not
predicted to alter DRD1 gene function. Furthermore, a sequence screen of the coding region of
the gene, with DNA from children who showed biased transmission of Haplotype 3, did not
reveal any variants. The present study tests the hypothesis that a disorder-causing variant,
associated with Haplotype 3, is in the 5'-regulatory region of this gene. We performed a sequence
screen of 2468 bp of the 5'-regulatory region of the gene in 41 children who showed biased
transmission of Haplotype 3. Sequence analysis revealed 3 nucleotide changes (variants) from the
published sequence, at -2115, -2031, and -1785 upstream from the translation start site. A search
for potential transcription factor (TF) binding sites showed that the change at -2115 resulted in
the loss of a potential Pax-4 binding site, and the gain of a potential Oct-1 binding site. The
change at -2031 resulted in the loss of a potential Pax-6 site and the gain of a potential CP2 site.
The change at -1785 did not result in a change in potential TF binding sites. These findings
suggest the possibility that changes at -2115 and -2031 might affect expression of the DRD1
gene, as a result of altered transcription factor binding.
49

41. Chan, E. 1 , Kovačević, N. 2 , Henderson, J. T. 3
1. Neuroscience Specialty, University of Toronto; 2. Department of Pharmceutical Sciences,
University of Toronto; 3. Mouse Imaging Centre, Hospital for Sick Children
THE DEVELOPMENT OF AN MRI BASED EXPERT SYSTEM AND 3D SURGICAL
MRI/CT ATLAS FOR 129/SvImJ AND C57BL6 INBRED MOUSE STRAINS
Mice are important animal models used to investigate the physiological and biochemical aspects
of a number of human diseases. Improvements in magnetic resonance imaging (MRI) and
computed tomography (CT) have progressed to the point where these techniques are applicable to
the analysis of small rodent physiology and structural morphology. In order to efficiently utilize
these tools for the analysis of structural perturbations in mice, one must first determine the levels
of natural variation which exists within structures such as the central nervous system (CNS) in
specific murine populations. In addition, one must develop a system for analyzing these data, in
which specific CNS components are automatically recognized and compared for the presence of
significant structural perturbations in terms of data obtained from control specimens. In order to
achieve this, an averaged atlas composed of >9 brains from a genetically inbred strain of mice
was produced (129/SvIMJ - N. Kovacevic). Neuroanatomic structures identifiable in each of the
9 composite brains (54) were then rendered in three dimensions by hand. These data were then
used to "teach" the computational expert system to correctly identify and characterized each
structure. This analysis system was then tested against several unknown (previously characterized
mutant) data sets in order to determine its accuracy. The results demonstrate that this system
reliably identified the indicated structures and correctly identified structural mutations in each
case. This system is presently being employed as part of a system of analytic tools to examine the
structure of the murine CNS in 3D at high throughput.
The second objective of my study was to create a three-dimensional surgical stereotactic atlas for
several mouse strains using data derived from MRI and computed tomography (CT). These
spatially accurate 3D atlases exhibited a far more accurate spatial representation of the murine
skull and brain than was previously possible using standard histologic techniques. The resulting
atlases demonstrate, in and to the ability to render a number of important neural interactions
within the CNS in 3D, the relative differences which exist between the brain and skull of 129Sv
versus C57B1 mice. These atlases are currently being employed to more accurately plan and
position stereotactic surgeries in the CNS. Data from these atlases has also been a key factor in
the development of a new system of stereotactic coordinates for the murine brain.
50

42. Cheung, Joyce
Department of Physiology
AGE-RELATED CHANGES IN THE PRODUCTION AND MIGRATION OF NEW
NEURONS IN THE RAT OLFACTORY SYSTEM
The subventricular zone (SVZ) is one area in the mammalian brain where neurogenesis continues
into adulthood. Many of the cells generated in the SVZ are neuronal precursors that migrate
tangentially along a pathway known as the rostral migratory stream (RMS) to the olfactory bulb
(OB) where they differentiate into local interneurons. The goal of the present study was to
identify age-related changes in neurogenesis in the SVZ. Young (1-2 months old) and middleaged
(12 months old) rats were injected with bromodeoxyuridine (BrdU) to label dividing cells
that were subsequently quantified. The neuronal phenotype of the newly generated cells was
confirmed by double-labeling the cells with doublecortin (DCX), a marker of young migrating
neurons. It was found that in young rats, proliferation of new cells occurred in the SVZ and
migrated via the RMS to the OB within 10 days. Middle-aged rats exhibited cell proliferation in
the SVZ, RMS, and OB, but fewer of the newly divided cells differentiated into neurons. In both
groups of animals, there appeared to be a second population of cells within the SVZ that was
characterized by delayed proliferation and migration that occurred between 10 and 28 days. This
study demonstrates novel mechanisms in the production and migration of new neurons from the
SVZ via the RMS to the OB.
Keywords: aging, cell proliferation, neurogenesis, subventricular zone, rostral migratory stream,
olfactory bulb, bromodeoxyuridine, doublecortin
51

43. Clarke, Laura, Georgiou, John, Salter, Michael, Roder, John
The Samuel Lunenfeld Research Institute
ROLES OF Src TYROSINE KINASE IN HIPPOCAMPAL SYNAPTIC PLASTICITY
Src is a non-receptor protein tyrosine kinase that is highly expressed in the CNS. Previous work
has suggested that Src plays an important role in the induction of long-term potentiation (LTP). In
the present study, we use a protein transduction domain to deliver Src(40-49), a peptide inhibitor
targeting the unique domain of Src, into intact cells, and show that late phase LTP in CA1 of the
hippocampus is unimpaired, while short-term forms of plasticity manifested immediately posttetanus
are reduced. This deficit was not accompanied by changes in basal transmitter release. We
also show that the Src family kinase inhibitors PP2 and SU6656 do not affect short-term forms of
plasticity, suggesting that the role of Src in short-term plasticity is mediated by protein-protein
interactions and not by its kinase activity. We propose several possible mechanisms through
which Src(40-49) may act in presynaptic terminals to transiently depress synaptic transmission
after the delivery of tetanic stimulation.
52

44. Ding, Hoi Ki, Ko, Shanelle, Shum, Fanny, Zhuo, Min
Department of Physiology, Centre for the Study of Pain, University of Toronto
A THERMAL-BASED ACTIVE ESCAPE/AVOIDANCE PARADIGM WITHOUT FEAR
Various analgesic tests measure the behavioural reactivity to different noxious sensations by
applying different sensory stimuli. In experimental studies, the hotplate is a common thermal
analgesic test for detecting both hyperalgesic and analgesic behavioural responses, while
Pavlovian fear conditioning is used to measure aversive fear memory. Based on a modified
hotplate test, we have developed an active escape/avoidance paradigm to test aversive memory
without the properties of fear, by using a thermal stimulus instead of an electrical shock. C57B1/6
demonstrated full learning and extinction curve, and repeated exposure to the thermal stimulus
did not alter pain reactivity. Escape latency was not altered when tested at 45°C, 35°C or at RT,
but was impaired when tested under altered contextual cues. CaMKIV KO mice were tested to
compare this paradigm with classic fear conditioning, and different types of receptors were
blocked to examine their effects on the learning and memory of this paradigm. CaMKIV KO
mice which were previously shown to have fear memory impairment have enhanced escape
latency. Injection of SQ22536 to block adenylyl cyclase impaired Day 1 escape latency, while
injection of MK801 to block NMDA receptors impaired acquisition of escaping behaviour.
Overall, the present results indicated that this thermal based active escape/avoidance paradigm
could be a simple method for studying aversive memories without the properties of fear, and
could be a useful test to detect performance and memory deficits related to aversive stimuli.
53

45. Hirshhorn, Marnie
Undergraduate Neuroscience Specialist Program
ASSESSING THE PRESENCE OF OSCILLATORY ACTIVITY IN THE THALAMUS OF
PARKINSON’S DISEASE PATIENTS
Parkinson's disease (PD) is a hypokinetic movement disorder characterized by difficulty in the
initiation of willed movements, muscular rigidity, and tremor of the hands and jaw at rest (Kandel
et al., 2000). Parkinson's patients are known to have a deficiency in the dopaminergic projection
from the Substantia Nigra to the striatum in the basal ganglia (BG). How this deficiency of
dopamine in the striatum contributes to the symptoms of PD remains unknown (Timmermmann
et al., 2003). Much of previous research has focused on changes in the firing rate of BG nuclei,
noting that the loss of dopamine in the striatum results in an increasing firing rate among the
output neurons of the BG (Obeso et al., 1997). This increases the inhibition of thalamocortical
neurons that facilitate movement, resulting in the hypokinetic symptoms characteristic of PD.
More recent research has begun to focus on changes in the patterns of activity in the BG and how
such changes relate to the symptoms of PD. A current hypothesis is that parkinsonian symptoms
result from abnormal synchronization of the BG that leads to a breakdown in the functional
segregation between parallel subcircuits of the BG-thalamocortical system (Levy et al., 2002).
Microelectrode single unit recordings have demonstrated synchronized oscillatory activity in the
subthalamic nucleus (STN) and the globus pallidus internus (GPi) at the frequency of
parkinsonian tremor (4-6 Hz) (Lemstra et al., 1999, Levy et al., 2002) and in the frequency range
of the beta band (11-30 Hz) (Levy et al., 2000). Based on these findings and the fact that the GPi
sends output to the thalamus, one would expect to observe oscillations at similar frequencies in
the thalamus (Niktarash, 2003). The present study analyzed microelectrode single unit recordings
of 27 thalamic cells from seven patients undergoing stereotactic surgery for bilateral deep brain
stimulation (DBS) to alleviate symptoms of PD. Autocorrelation histograms and spectral analysis
showed that 86% of cells had rhythmic activity at a mean frequency of 3.16 Hz. These results do
not support the hypothesis that thalamic cells should oscillate within a similar frequency range as
cells in the STN and GPi.
54

46. Ng, Karen
Undergraduate Neuroscience Specialist Program
INVESTIGATING THE ROLE OF THE m5 CHOLINERGIC RECEPTOR IN BRAIN
STIMULATION REWARD USING PHAMACOLOGICAL AND ELECTROPORATION
TECHNIQUES
The M5 receptor is one of five cholinergic muscarinic receptor subtypes. It is associated with
dopamine neurons in the brain. The dopaminergic system has, in the past, been linked to reward
seeking behaviour. Therefore, in order to investigate the role of the M5 muscarinic receptor and
dopamine neurons, the brain stimulation reward paradigm in rats is utilized as a behavioural
measure for pharmacological manipulations and electrophysiological manipulations. The
simultaneous nicotinic antagonist mecamylamine (30 ug/0.5 uL) and the muscarinic antagonist
atropine (30 ug/0.5 uL) infusion and atropine (30 ug/0.5 uL) alone was injected into the VTA.
M5 receptor expression was then increased in the ventral tegmental area by electroporation. The
combination intracranial infusion of mecamylamine and atropine, as well as intracranial infusions
of atropine did not significantly shift self-stimulation threshold. After M5 receptor expression
was increased, self-stimulation threshold was not significantly increased compared to the control
animal. Two animals, however, did demonstrate a significant change in self-stimulation
frequency. After applying a Bonferonni correction, one animal displayed an increase in selfstimulation
threshold (t =38.17, df=2, p>0.05), suggesting a VTA lesion, and another animal
displayed a decrease in self-stimulation threshold (t=8.08, df=2, p>0.05). The results of these
studies also suggest that further investigations should be conducted to reduce damage, and
increase gene uptake in order to obtain more definitive results.
55

47. Rizvi, Sakina
Undergraduate Neuroscience Specialist Program
MEMORY DEFICITS AMONG PERSONS WITH SCHIZOPHRENIA: UTILITY OF THE
NINE-BOX MAZE TASK
It is now well established that the hippocampus (HF) is a central site of pathology in
schizophrenia (Nelson et al, 1998), and as such schizophrenic patients may exhibit a specific
profile of memory loss that is associated with HF-damage. Namely, they may exhibit specific
deficits in spatial, working and allocentric memory. In this study, we utilize the nine-box maze
task (NBMT) to test the HF-related memory loss that occurs in schizophrenia. Though the NBMT
has been used to effectively test memory deficits associated with HF pathology in humans
(Abrahams, 1997), it has never been used to test memory impairment in schizophrenia. In
addition, the NBMT is one of the few human paradigms that exist that can effectively test the
three memory dimensions associated with HF-damage. As predicted, schizophrenia patients
exhibited a specific memory loss on the NBMT component that required allocentric, spatial, and
working memory. The present findings are relevant in that we have demonstrated that
schizophrenia patients exhibit memory loss that is highly related to HF pathology.
56

48. Salmasi, Giselle Ghazal
Neuroscience Research, Department of Laboratory Medicine and Pathobiology, Sunnybrook and
Women’s College Health Sciences Centre, University of Toronto
DRAINAGE OF CEREBROSPINAL FLUID INTO EXTRACRANIAL LYMPHATICS IN
RATS AND MICE REVEALED BY INTRACISTERNAL INJECTION OF MICROFIL
Cerebrospinal fluid (CSF) drainage has conventionally been thought to occur through arachnoid
granulations and villi into the superior sagittal sinus. However, the clinical experience and
experimental data in animals suggests that this view is most likely incorrect. Numerous
anatomical and quantitative physiological investigations into CSF transport have shown that
extracranial lymphatics play a significant role in CSF absorption. A particularly well-documented
route of CSF drainage relates to CSF transport through the cribriform plate in association with
olfactory nerves. Lymphatics in the submucosa of the olfactory and respiratory epithelium absorb
the CSF that has drained via this pathway. To date, the most convincing work on CSF drainage
mechanisms (qualitative as well as quantitative) has been carried out in sheep. This work suggests
the possibility that lymphatic vessels are involved in the pathogenesis of hydrocephalus.
However, the existing genetic and induced hydrocephalus models are largely confined to rodents.
In order to take advantage of these interesting animal correlates of disease it will be important to
establish the connections between the CSF and lymph compartments in rats and mice. These
models will allow us to test new and innovative ideas about how hydrocephalus may come about,
namely through a possible impairment in the lymphatic drainage of CSF.
The objective of my study was to visualize CSF-lymphatic linkages in wild-type rodents. To
achieve this, yellow Microfil was injected post mortem into the cisterna magna of mice (n=15)
and rats (n=5) to perfuse the cranial subarachnoid compartment and follow normal CSF drainage
routes out of the cranial vault. Microfil was observed at numerous locations extracranially. In
both the mouse and rat, there was extensive filling of lymphatics in the olfactory and respiratory
submucosa and in the nasal mucosa. These included lymphatics covering the ethmoid turbinates,
the nasal septum, and the lateral walls of the nasal cavity. Additionally, filling of lymphatic
vessels in the vomeronasal organ was noted. Furthermore, Microfil was seen terminating at the
retropharyngeal and cervical lymph nodes in the mouse and at the cervical lymph node in the rat.
These results confirm the existence of CSF-lymph linkages in rodents and support the role of
lymphatics in CSF drainage in many species. These results also indicate that additional
investigation of the lymphatic CSF drainage pathways in various rodent models of hydrocephalus
may reveal new insights into the pathogenesis of this disorder and could lead to new therapeutic
approaches for the treatment of ventricular dilation in children and adults.
Supported by the Canadian Institute of Health Research (CIHR)
57

49. Watts, Jeff
Undergraduate Neuroscience Specialist Program
CAN DIFFERENCES IN THE Ca 2+ SENSOR EXPLAIN DIFFERENCES IN QUANTAL
OUTPUT BETWEEN CRAYFISH TONIC AND PHASIC CELLS A MONTE CARLO
MODEL
Evoked neurotransmitter release requires Ca 2+ entry into the presynaptic terminal. This increase
in Ca 2+ concentration is thought to be detected by several different sensors, the primary being
synaptotagmin-1. Once Ca 2+ binding to synaptotagmin-1 occurs at a vesicle that has been primed
for release, the vesicle fuses with the presynaptic membrane, dumping its contents into the
synaptic cleft. Different types of neurons display varying patterns of neurotransmitter release;
tonic and phasic axons synapsing on the crayfish opener muscle show up to a 1000-fold
difference in neurotransmitter release per action potential. A Monte Carlo model was constructed
of a crayfish tonic active zone, and then differences in the binding properties of synaptotagmin-1
were examined to determine what is necessary to reproduce the difference in neurotransmitter
release found in tonic and phasic cells. A fifteen-fold difference in Ca 2+ binding affinity of
synaptotagmin-1 was necessary to reproduce a 200-fold difference in neurotransmitter release.
The current model did not take into account Ca 2+ dependence of synaptotagmin-l-phospholipid
interactions. If this fact were to be accounted for, it is possible that a four-fold difference in Ca 2+
binding affinity would produce the same result.
58

50. Wong, Fiona
Undergraduate Neuroscience Specialist Program
H1, A STABLE HEPOXILIN ANALOG, DOES NOT ENHANCE NEURITE OUTGROWTH
OR REGENERATION AFTER INJURY IN RAT PHEOCHROMOCYTOMA CELLS OR
PRIMARY HIPPOCAMPAL NEURONS IN VITRO
Hepoxilins are 12(S)-lipoxygenase metabolites of arachidonic acid found in the CNS that have
recently been implicated in growth factor-dependent neurite outgrowth and regeneration. We
investigated the effects of a chemically synthesized stable hepoxilin analog, H1 (methyl 8-
hydroxy-11,12-cyclopropyl HxA 3 ), in in vitro models of spinal cord injury using rat
pheochromocytoma (PC 12) cells and primary hippocampal neurons. 0.1 µM DMSO control and
0.28 µM H1 treatments to PC 12 cells and hippocampal neurons were compared in order to
determine if H1 had any effects neurite outgrowth, regeneration, dendritic spine formation, and
calcium dynamics. At a dose of 0.28 µM, Hl was non-toxic to cells but did not significantly
enhance neurite outgrowth or regeneration 8 h or 48 h post-injury. DiIC 12 (3)-stained hippocampal
neurons 48 h after H1 treatment failed to show any conclusive evidence for dendritic spine
formation or growth due to floating debris and possible fixation artifacts. Optimized fluo-3
calcium imaging showed that H1 did not significantly increase intracellular calcium levels or
dynamics. Overall, these results suggest that HI does not have any effect in enhancing neurite
outgrowth and regeneration, or altering intracellular calcium levels in PC 12 cells and primary
hippocampal neurons.
59

51. Wong, J.S., Hutchison, W.D.
Department of Physiology, Faculty of Arts and Science and Faculty of Medicine, University of
Toronto, Ontario, Canada
6-HYDROXYDOMAPINE REDUCES MOTOR BEHAVIORS OF RATS AND INDUCES
DISTINCT FIRING PATTERNS IN MULTI-UNIT RECORDINGS OF THE RODENT
GLOBUS PALLIDUS
Idiopathic Parkinson's disease is mainly attributed to the losses of dopaminergic neurons in the
nigrostriatal pathway. It is widely accepted that the loss of dopamine in striatal synapses lead to
paradoxical increases in firings of GABAnergic neurons projecting to the external globus
pallidus, leading to inhibition of the nucleus and increasing activation of the indirect stop
pathway ultimately. In this study, rodent Parkinsonian models are constructed by infusions of 6-
hydroxydopamine into the medial forebrain bundle, causing lesions of nigrostriatal dopaminergic
neurons. The open field test over the course of 40 days suggests progressive declines in motor
behaviors of the rats after 6-hydroxydopamine administrations. Rotation test was employed to
screen the efficacy of 6-hydroxydopamine on destroying the nigrostriatal dopaminergic neurons,
and only two of the rats had sufficient contralateral rotations 20 minutes after apomorphine (D1,
D2 nonselective agonist) injection for them to be considered satisfactory Parkinsonian models.
Detailed multi-unit electrophysiological profile on 3 different sites of the globus pallidus (rodent
homologue of external globus pallidus) produced several findings. Firing rates of some cells
gradually decreased after apomorphine injection, which contradicts with the current pathological
model of Parkinson's disease. β-bands with frequencies between 11 and 30 Hz were identified in
cross-correlations of different sites in the globus pallidus, previously identified in subthalamic
nuclei of Parkinsonian objects. Slow wave recordings suggest that they are possibly triggered by
high amplitude spikes in the globus pallidus or the subthalamic nucleus. This study provides a
novel approach to evaluate motor behaviors in pathological models of the motor system. Most
importantly, electrophysiological analyses of firing patterns suggest that the current model of
idiopathic Parkinson's disease may have undermined the role of interactions between the external
globus pallidus and subthalamic nucleus.
Keywords: apomorphine; external globus pallidus; motor behavior; multi-cell recording;
Parkinson's disease; rat; 6-hydroxydopamine
60

52. Yum, Jennie
Department of Neuroscience, University of Toronto, Toronto, Ontario, Canada, M5S 3G3
SHORT-TERM DEPRESSION AT THE DEVELOPING CALYX OF HELD SYNAPSE:
EVIDENCE FOR HETEROSYNAPTIC INHIBITION MEDIATED BY PRESYNAPTIC
GABA B RECEPTORS
Activity-dependent depression is an integral component of short-term plasticity at the calyx of
Held synapse. We examined synaptic depression in postnatal day (P) 10-16 mice and found that
depression may be induced by endogenous release of neurotransmitter in response to
physiological patterns of stimuli. EPSCs were elicited by afferent fibre stimulation of 100Hz
bursts for 30ms each, separated by varying inter-burst intervals (in the range of 0.25s to 10s).
Successive bursts generated EPSCs that declined in amplitude. Depression was found to be
frequency-dependent, increasing as the interval between bursts decreased from 10s to 0.25s. In
order to examine the impact of stage of development, cells were divided into two age groups:
those prior to hearing onset (P10-12) and those after (P13-16). Depression was further found to be
age-dependent, being more robust at immature synapses. At P10-12, EPSC amplitudes declined
to 44.6 ± 3.27% of initial levels, while at P13-16, amplitudes declined to 57.6 ± 3.14%. Finally,
we have shown that the degree of depression was enhanced when stimulating at 3x the initial
stimulation voltage (threshold) which recruits minor perisynaptic inputs. At P10-12, stimulating
at 1x reduced EPSC amplitudes 85.3 ± 3.12% and stimulating at 3x reduced amplitudes to 77.5 ±
3.67%. At P13-16, the reduction was from 84.3 ± 3.26% to 79.6 ± 2.20%. P