The 2009 Neuroscience poster day was held Thursday April 16 2009 by liuqingyan

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									The 2009 Neuroscience poster day was held Thursday April 16 2009 in conjunction with Dr. McBain's
Distinguished Lecture.

Download the full poster list

Congratulations to the five top posters:

    •   Alonso Martinez-Canabal|
        Title: Chronic over-expression of transforming growth-factor beta1 (tgf-b1) negatively impacts
        brain function and cognition

    •   A.J. Marsolais
        Title: The role of notch signaling in learning and memory

    •   R.H.C. Chen
        Title: Characterization of rab3a and α-synuclein interaction and consequences on α-synuclein
        compartmentalization

    •   Norman Farb
        Title: Letting go of sadness: mindful detachment in emotion regulation

    •   L. Zavalishina
        Title: Mbd2, another methyl-cpg-binding protein, contributes to autism-like behavioural
        phenotype in mice


Each won a $100 gift certificate to the UofT Bookstore. Thank you to all those who presented and
attended and a very special thank you to the poster judges.
      University of Toronto Neuroscience Program




                   ANNUAL
               POSTER DAY
Collaborative Graduate Program in Neuroscience


                 Thursday, April 16, 2009



          Medical Sciences Building, Stone Lobby,

                   University of Toronto
                                        Schedule
10:00-11:00   Registration (free), Poster set up
              Medical Sciences Building, Stone Lobby
10:00-11:00   Poster viewing
              Medical Sciences Building, Stone Lobby
11:00-2:00    Poster Presentations

  12:00-1:00 Pizza Lunch
  12:00-2:00 Poster Judging
2:00-3:00     UTNP Distinguished Lectureship Series – Dr. Chris McBain, Rm 3154 MSB
              National Institutes of Health Eunice Kennedy Shriver National Institute of Child
              Health and Human Development Program in Developmental Neuroscience,
              Bethesda, Maryland USA
              "mGluR7, a bidirectional switch controlling plasticity in a hippocampal
              feedforward inhibitory circuit"
              Host: Michelle Aarts




                                            -2-
                                                     Posters

1. Adusei, Daniel C.*; Pacey, Laura K.; Hampson, David R.
   Department of Pharmaceutical Sciences, University of Toronto
   DEVELOPMENTAL CHANGES IN GABAERGIC PROTEIN EXPRESSION IN FRAGILE X KNOCKOUT MICE

2. Agnihotri, Sabrina*1; Colantonio, Angela1,2,3; Polatajko, Helene1,2; Cameron, Deb1,2; Rumney, Peter4;
   Wiseman-Hakes, Catherine1,2; Bridger, Leslie; Keightley, Michelle L1,2,4
   1
    Graduate Department of Rehabilitation Science (University of Toronto), 2Department of Occupational
   Science and Occupational Therapy (University of Toronto), 3Toronto Rehabilitation Institute, 4Bloorview
   Kids Rehab
   EXPRESSIVE ARTS AS A SOCIAL AND COMMUNITY PARTICIPATION TOOL FOR ADOLESCENTS WITH
   ACQUIRED BRAIN INJURY

3. Ahmadi, Negar*1,2; Shapiro, Colin M1,2,3
   1
     Department of Cell and Systems Biology, University of Toronto, 2Toronto Western Research Institute,
   University Health Network, 3Department of Psychiatry, Faculty of Medicine, University of Toronto
   INVESTIGATION OF SLEEP IN CHRONIC TREATMENT-RESISTANT DEPRESSED PATIENTS

4. Alves, Nyresa C.* 1; Bailey, Craig D.C. 1; Nashmi, Raad2; Lambe, Evelyn K.1
   1
     Department of Physiology, University of Toronto; 2Department of Biology, University of Victoria
   DEVELOPMENTAL SEX DIFFERENCES IN Α4Β2* NICOTINIC CURRENTS IN LAYER VI PYRAMIDAL NEURONS
   OF RODENT PREFRONTAL CORTEX

5. Andre, Melanie*1,5,7; Anderson, Nicole D.3,4,5,7; Stuss, Donald T.1,3,4,6; Dawson, Deirdre R.1,2,5,7
   1
    Graduate Department of Rehabilitation Science, and Departments of 2Occupational Science &
   Occupational Therapy, 3Psychology, and 4Medicine, University of Toronto;
   5
    Kunin-Lunenfeld Applied Research Unit; 6The Rotman Research Institute, Baycrest; 7Toronto
   Rehabilitation Institute
   FURTHER EXPLORATION OF THE ECOLOGICAL VALIDITY OF TESTS OF EXECUTIVE FUNCTION

6. Antflick, Jordan E.*1; Vetiska, Sandra1; Baizer, Joan S.2; Yao, Yi1; Baker , Glen B.3; David R. Hampson1,4
   1
    Leslie Dan Faculty of Pharmacy;2Department of Physiology and Biophysics, the University at Buffalo,
   Buffalo, New York; 3Neurochemical Research Unit and Bebensee Schizophrenia Research Unit, Dept. of
   Psychiatry, University of Alberta, Edmonton, Alberta, Canada;4Department of Pharmacology, University
   of Toronto, Toronto, Ontario, Canada,
   IS L-PHOSPHOSERINE A NEUROTRANSMITTER IN THE CENTRAL NERVOUS SYSTEM?




                                                         -3-
7. Arundine, A*1,2;Bradbury C1; Ruttan, L1; Green, REA1,2
   1
    Toronto Rehabilitation Institute, 2University of Toronto, Graduate Department of Rehabilitation Science
   EXAMINING LONG-TERM EFFICACY AND COMMUNITY INTEGRATION BENEFITS OF A COGNITIVE
   BEHAVIOUR THERAPY PROTOCOL ADAPTED FOR PEOPLE WITH BRAIN INJURY

8. Bae, James J.1,3*; Martinez-Canabal, Alonso2,4; Frankland, Paul.W. 1,2,4; Lu, Wei-Yang1-3
   1
    Department of Physiology; 2Institute of Medical Science, University of Toronto, Toronto, ON.;
   3
    Neuroscience Research, Clinical and Integrative Biology, Sunnybrook & Women's College Health
   Sciences Centre, Toronto, ON; 4Program in Neurosciences and Mental Health, Hospital for Sick Children,
   Toronto, ON.
   INCREASED EXPRESSION OF TRANSFORMING GROWTH FACTOR-β1 ALTERS SYNAPTIC STRUCTURE AND
   GLUTAMATE RECEPTOR EXPRESSION

9. Buske, Christine*; Gerlai, Robert
   Cell & Systems Biology, Collaborative Program in Neuroscience
   TEMPORAL CHARACTERISTICS OF SHOALING BEHAVIOR OF ZEBRAFISH: LARGE SCALE DEVELOPMENTAL
   AND FINE RESOLUTION CHANGES.

10. Chee, Justin*1; Tremblay, Luc2; Zabjek, Karl1
    1
     Graduate Department of Rehabilitation Science; 2.Faculty of Physical Education and Health
    THE EFFECT OF MECHANICAL AND SENSORIMOTOR PERTURBATIONS ON THE PHYSIOLOGICAL COST OF
    WALKING

11. Blankstein, Udi 1, 2*; Chen, Jerry 1, 2*; Mincic, Adina2; Davis Karen D.1, 2
    1
     Institute of Medical Science, University of Toronto; 2Division of Brain, Imaging and Behaviour – Systems
    Neuroscience, Toronto Western Research Institute, University Health Network, Toronto, Ontario,
    Canada, M5T 2S8
    * co-first authors (these authors contributed equally)
    NEUROANATOMICAL CORRELATES OF NEUROTICISM AND EXTRAVERSION IN HEALTHY ADOLESCENTS

12. Chen, R.H.C.1*; Visanji N.2; Stanciu M.2; Mount H.T.J.1,2; Tandon A.2
    1
     Department of Physiology; 2Institute of Medical Science, Centre for Research in Neurodegenerative
    Diseases, Faculty of Medicine, University of Toronto, 6 Queen’s Park Crescent West, Toronto, Ontario,
    Canada, M5S 3H2.
    CHARACTERIZATION OF RAB3A AND Α-SYNUCLEIN INTERACTION AND CONSEQUENCES ON Α-SYNUCLEIN
    COMPARTMENTALIZATION




                                                       -4-
13. Cumyn, Elizabeth M.*1,2; Yang, Jimau 1, Robinson, Brian H.3,4; Mount, Howard T. J.1,2,5
    1
     Centre for Research in Neurodegenerative Diseases; 2Institute of Medical Science; 3Dept. Biochemistry;
    4
     Hospital for Sick Children; 5Dept. Medicine (Div. Neurology)
    DISTINCT EFFECTS OF WILD-TYPE, A53T AND A30P α-SYNUCLEIN TRANSGENES ON BIOENERGETIC
    HOMEOSTASIS IN MOUSE BRAIN

14. DeSouza, Danielle*1,2; Mikulis, Dr. David3,4; Lerch, Dr. Jason5,6, Glazer, Joanna2; Green, Dr. Robin1,2
    1
     Graduate Department of Rehabilitation Science, University of Toronto; 2Toronto Rehabilitation
    Institute; 3Toronto Western Research Institute; 4Department of Medical Imaging, University of Toronto;
    5
     Department of Medical Biophysics, University of Toronto; 6Toronto Centre for Phenogenomics: MICe
    AN EXAMINATION OF THE BRAIN?S STABILITY FOLLOWING TRAUMATIC BRAIN INJURY USING MR-
    DERIVED VOLUMETRIC AND CORTICAL THICKNESS MEASURES: A LONGITUDINAL STUDY

15. Elbert, Adrienne*; Gomez, Lissette; Cate-Carter, Tasha; Wigg, Karen; Feng, Yu; Archibald, Jennifer;
    Anderson, Barbara; Kerr, Elizabeth; Lovett, Maureen; Humphries, Tom; Barr, Cathy
    University of Toronto: Institute of Medicine and Department of Psychiatry
    READING DISABILITIES: ROLE OF POLYMORPHISMS IN CANDIDATE GENES ON CHROMOSOME 6P
16. Farb, Norman*1; Anderson, Adam1; Segal, Zindel2
    1
     Department of Psychology, University of Toronto; 2Centre for Addiction and Mental Health, University
    of Toronto
    LETTING GO OF SADNESS: MINDFUL DETACHMENT IN EMOTION REGULATION

17. Fenili, Daniela*; McLaurin, JoAnne
    Centre for Research in Neurodegenerative Diseases, Department of Laboratory Medicine and
    Pathobiology, Collaborative Program in Neuroscience, University of Toronto
    CHARACTERIZATION OF INOSITOL TRANSPORTERS AS A METHOD FOR DRUG DELIVERY TO THE CNS

18. Gardezi, Sabiha; Li, Qi; Stanley, Elise F.
    Genetics and Development Division, Toronto Western Research Institute, University Health Network,
    N-TYPE CALCIUM CHANNEL DOES NOT INTERACT DIRECTLY WITH PDLIM5

19. Gauster, Andrea*; Yunusova, Yana
    Department of Speech-Language Pathology, University of Toronto
    EFFECT OF SPEAKING RATE ON MEASURES OF VELOPHARYNGEAL FUNCTION




                                                       -5-
20. Goodfellow, Nathalie M.1; Benekareddy, Madhurima2; Vaidya Vidita A.2; Lambe, Evelyn K.1,3
    1
     Department of Physiology, University of Toronto, Toronto Ontario Canada; 2Department of Biological
    Sciences, Tata Institute of Fundamental Research, Mumbai, India; 3Department of Obstetrics and
    Gynaecology, University of Toronto.
    LAYER II/III OF THE PREFRONTAL CORTEX: INHIBITION BY THE SEROTONIN 5-HT1A RECEPTOR IN
    DEVELOPMENT AND STRESS

21. Grieder, Taryn *; Sellings, Laurie H.; -Kee, Ryan Ting-A; van der Kooy, Derek
    Institute of Medical Science, University of Toronto, Canada.
    DOPAMINERGIC SIGNALING MEDIATES NICOTINE DEPENDENT WITHDRAWAL AVERSIONS BUT NOT THE
    MOTIVATIONAL EFFECTS OF ACUTE NICOTINE WITHDRAWAL

22. Hammad, Sherief* ;Kennedy, John M.
    Department of Life Science, University of Toronto at Scarborough, Toronto, ON
    ANGLE ILLUSION WITH CONVERGENCE AND NO FORESHORTENING

23. Ho, Ernest C. Y. 1,2*; Zhang, Liang2,3; Skinner, Frances K. 1,2,3,4
    1
     Department of Physiology; 2Toronto Western Research Institute, University Health Network;
    3
     Department of Medicine (Neurology); 4Institute of Biomaterials and Biomedical Engineering, University
    of Toronto.
    MATHEMATICAL ANALYSES AND SIMULATIONS GIVE RISE TO A NOVEL HYPOTHESIS FOR THE
    EMERGENCE OF SLOW POPULATION RHYTHMS

24. Huang, Lili*; Kanungo, Anish K.; Henderson, Jeffrey T.
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario,
    Canada.
    THE ROLE OF SMAC/DIABLO IN REGULATING PROGRAMMED CELL DEATH OF MOTOR NEURONS AND
    SYMPATHETIC NEURONS

25. Hui, Kelvin K.W.*1; Liadis, Nicole2; Robertson, Jennifer3; Kanungo, Anish1; Henderson,
    Jeffrey T.1
    1
     Department of Pharmaceutical Sciences, University of Toronto; 2Department of Medical Biophysics,
    Faculty of Medicine, University of Toronto; 3Department of Pathology and Molecular Medicine, Faculty
    of Health Sciences, McMaster University
    MOLECULAR MECHANISM OF NEUROPROTECTION MEDIATED BY IMMUNOPHILIN LIGANDS

26. Hui, Kwokyin*; Fernandes, Abigail; Luu, Michael; Lan, Freeman; Feng, Zhong-Ping
     Department of Physiology, University of Toronto.
    INSIGHTS INTO REAL-TIME PCR: A METHOD TO IDENTIFY TREATMENT EFFECTS AND OUTLIERS




                                                     -6-
27. Kim, Hyunhee*; Wong, Fiona F.*; Stanley, Elise F.
    Dept. of Physiology
    CHOLINERGIC TRANSMISSION FROM SCHWANN CELLS ONTO DRG NEURON SOMATA

28. Janus Monika*; Lewis, Marc
    Department of Human Development and Applied Psychology, OISE/UT
    ERP RESPONSE ASSOCIATED WITH EMOTION REGULATION ON A GO/NO-GO TASK IN NORMAL CHILDREN

29. Kirshenbaum, Greer*; Duffy ,Steven; Roder, John
    Institute of Medical Science and Program in Neuroscience
    MUTATIONS IN THE ALPHA-3 SODIUM POTASSIUM PUMP UNDERLIE A MOUSE MODEL OF BIPOLAR
    DISORDER

30. Kostelecki, Wojciech*;Velazquez, Jose Luis Perez
    Institute of Medical Science
    INFERENCE OF DIRECTED CORTICAL PROCESSING FROM MEG RECORDINGS

31. Labrie, Viviane1,2*; Fukumura, Ryutaro3; Rastogi, Anjali4; Fick, Laura J.5; Wei, Wang6; Boutros, Paul C.7;
    Kennedy, James L.8; Semeralul, Mawahib O.8; Lee, Frankie H.4; Baker, Glen B.9; Belsham, Denise D.5;
    Barger, Steven W.6,10; Gondo, Yoichi3; Wong, Albert H.C.8; Roder, John C.1,2
    1
     Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; 2*Institute
    of Medical Science and Program in Neuroscience, University of Toronto, Toronto, ON M5S 1A8, Canada;
    3
     Mutagenesis and Genomics Team, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba 305-0074, Japan;
    4
     Department of Pharmacology, University of Toronto, ON M5S 1A8, Canada; 5Department of Physiology,
    University of Toronto, ON M5S 1A8, Canada; 6Department of Neurobiology & Developmental Sciences,
    University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; 7Ontario Institute for Cancer
    Research, MaRS Center, Toronto, ON M5G 0A3, Canada; 8Neuroscience Division, Center for Addition and
    Mental Health, Toronto, ON M5T 1R8, Canada; 9Neurochemical Research Unit and Bebensee
    Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2G3,
    Canada; 10Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205,
    USA.
    GENETIC INACTIVATION OF SERINE RACEMASE PRODUCES BEHAVIORAL PHENOTYPES RELATED TO
    SCHIZOPHRENIA IN MICE

32. Chinta Venkateswararao, Lakshminarayan 1*; Tweed, Douglas1,2,3
    Departments of Physiology1 and Medicine2, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
    Centre for Vision Research3, York University, Toronto, Ontario M3J 1P3, Canada
    OPTIMAL SENSORIMOTOR CONTROL WITHOUT WEIGHT TRANSPORT




                                                       -7-
33. Lakhani, Ekta*1,2,3; Wright, Tom2,3 Glazer, Peter3; Westall Carol1,3
    1
     Institute of Medical Science, University of Toronto; 2Ophthalmology and Vision Science, University of
    Toronto; 3Hospital for Sick Children
    CAN ELECTROPHYSIOLOGICAL MARKERS PREDICT DIABETIC RETINOPATHY?

34. Lee, Esther1*; Steidl, Stephan2 ; Yeomans, John S. 1,2,3
    1
     Department of Cell & Systems Biology, University of Toronto, Toronto, ON; 2Department of Psychology,
    University of Toronto, Toronto, ON; 3Centre for Biological Timing and Cognition (CBTC)
    OPIATE-INDUCED LOCOMOTION DEFICITS IN M5 MUSCARINIC RECEPTOR KNOCKOUT MICE ARE
    REVERSED AFTER FOOD DEPRIVATION

35. Lee J.-C.*; Sood M.; Sessle B.J.
    Faculty of Dentistry, University of Toronto, Canada
    OPERANT CONDITIONING OF TONGUE PROTRUSION IN MONKEYS (MACACA FASCICULARIS)

36. Lipszyc, Jonathan*; Schachar, Russell
    Institute of Medical Science
    INHIBITORY CONTROL AND PSYCHOPATHOLOGY: A META-ANALYSIS OF STUDIES USING THE STOP
    SIGNAL TASK

37. Liu, Zhongxu*; Lewis, Marc D.
    Department of Human Development and Applied Psychology, University of Toronto
    CHILDREN’S BRAIN SIGNAL VARIABILITY AND BEHAVIORAL PERFORMANCE
38. Lu, T.Z.*; Feng, Z.P.
     Department of Physiology, Faculty of Medicine, University of Toronto, 1 King’s College Circle, Toronto,
    Ontario, Canada, M5S 1A8.
    FUNCTIONAL STUDY OF A NON-SELECTIVE CATION CHANNEL IN AERIAL RESPIRATORY MODEL -
    LYMNAEA STAGNALIS

39. Marsolais, A.J.1,2; Sheth, R.1,3; Yiu, A.P.1,4; Egan, S.E.1,5; Josselyn, S. A.1,2,4
    1
     The Hosp Sick Children, Toronto, ON, Canada; 2Physiol.,3Hum. Biol., 4Inst. of Med. Sci.,5Mol. Gen., Univ.
    of Toronto, Toronto, ON, Canada
    THE ROLE OF NOTCH SIGNALING IN LEARNING AND MEMORY




                                                       -8-
40. Martinez-Canabal, Alonso*1, 2; Lerch, Jason5; Buckwalter, Marion4; Spring, Shoshana5; Sled, John5,6;
    Wyss-Coray, Tony4; Frankland, Paul William1,2,3.
     1
      Department of Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1X8
    Canada; 2Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8 Canada;
    3
     Department of Physiology, University of Toronto, ON M5S 1A8 Canada; 4Department of Neurology and
    Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA; 5Mouse
    Imaging Centre, Hospital for Sick Children, Toronto, ON M5T 3H7 Canada; 6Department of Medical
    Biophysics, University of Toronto, Toronto, ON M5G 2M9 Canada.
    CHRONIC OVER-EXPRESSION OF TRANSFORMING GROWTH-FACTOR BETA1 (TGF-B1) NEGATIVELY
    IMPACTS BRAIN FUNCTION AND COGNITION

41. Nejatbakhsh, N1*; Guo CH1; van Kesteren RD2; Feng ZP1
    1
     Dept. of Physiology, University of Toronto, Toronto, Ontario, Canada; 2Dept. of Molecular & Cellular
    Neurobiology, Vrije Universiteit, Amsterdam, The Netherlands
    REGENERATION OF CENTRAL NEURONS IN LYMNAEA REQUIRES LOCAL SYNTHESIS OF A NOVEL CALCIUM
    BINDING PROTEIN

42. Pacey, Laura K.K.1; Heximer, Scott P.2; Hampson, David R.1,3
    1
     Leslie Dan Faculty of Pharmacy ; Departments of 2Physiology and 3Pharmacology, University of Toronto
    RESCUE OF AUDIOGENIC SEIZURES IN FRAGILE X AND RGS4 DOUBLE KNOCKOUT MICE

43. Pisterzi Luca F.1*; Stoneman, Michael R.2, Wells James W. 1; Raicu, Valerică2
    1
     Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON; 2Departments of Physics and
    Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI.
    OLIGOMERIC SIZE OF THE M2 MUSCARINIC RECEPTOR IN LIVE CELLS AS DETERMINED FROM FRET
    EFFICIENCIES AT THE LEVEL OF SINGLE PIXELS

44. Proulx, Éliane1*;Young, Edwin J.2; Osborne, Lucy R.2; Lambe, Evelyn K.1,3
    1
     Departments of Physiology; 2Molecular Medical Genetics; 3Obstetrics and Gynecology, Faculty of
    Medicine, University of Toronto
    ALTERED PREFRONTAL MODULATION IN A TRANSGENIC MOUSE WITH A LOW ANXIETY PHENOTYPE

45. Ratnam, Melanie *; Aarts, Michelle
    University of Toronto, Cell and Systems Biology; Centre for the Neurobiology of Stress
    TRPM2 & TRPM7: CELL-SPECIFIC EXPRESSION IN THE BRAIN

46. Rosenzweig, S*; Czerwinska E; Orser B.A.; Wojtowicz J. M.
    Departments of Physiology, Faculty of Medicine, University of Toronto.
    ABNORMAL DEVELOPMENT OF ADULT BORN NEURONS IN THE DENTATE GYRUS OF GABAAR-DELTA
    KNOCKOUT MICE




                                                      -9-
47. Rowland, James W. *; Lee, Jason J.; Schut, Desiree; Eftekharpour, Eftekhar; Fehlings, Michael G.
    Institute of Medical Science, Toronto Western Research Institute, University Health Network, Division of
    Neurosurgery, University of Toronto.
    ASSESSING THE ABILITY OF PRIMITIVE NEURAL STEM CELLS DERIVED FROM MOUSE EMBRYONIC STEM
    CELLS THROUGH A DEFAULT MECHANISM TO PROMOTE REMYELINATION OF DYSMYELINATED CNS
    AXONS

48. Sam, Kevin*; Aarts, Michelle M.
    Cell and Systems Biology, University of Toronto
    CHARATERIZATION OF BINDING PARTNERS OF THE NMDAR NR2 SUBUNITS

49. Siddiq, Ishita*;Park, Eugene; Liu, Elaine;Baker, Andrew
    Cara Phelan Center for Trauma Research, St. Michael's Hospital, Toronto; Institute of Medical Science,
    Faculty of Medicine, University of Toronto
    UPREGULATION OF VEGF-A USING ENGINEERED ZINC FINGER PROTEIN GENE THERAPY REDUCES
    APOPTOTIC CELL DEATH AFTER LATERAL FLUID PERCUSSION INJURY IN RATS

50. Sinopoli, Katia J.*; Max, J.; Levin, H.; Li, X.; Schachar, R.; Dennis, M.
    *Department of Psychology and the Collaborative Program in Neuroscience, University of Toronto, and
    the Program in Neurosciences and Mental Health, the Hospital for Sick Children
    RELATIONS AMONG MECHANISM OF INJURY, INJURY SEVERITY, AGE AT INJURY, AND PRE-MORBID
    BEHAVIOURS IN CHILDHOOD TRAUMATIC BRAIN INJURY

51. Srejić, Luka R *1,3,5; Aarts, Michelle6; Hutchison, William D2,3,4
    1
     Div’s of Fundamental Neurobiology & 2Brain Imaging and Behaviour, Toronto Western Research
    Institute; Dept’s of 3Surgery, 4Physiology and 5Cell and Systems Biology, Univ. of Toronto; 6Life Sciences,
    Biology, Univ. of Toronto at Scarborough
    APPLICATION OF TAT-NR2B9C LEADS TO ENHANCED RECOVERY OF SPONTANEOUS AND EVOKED
    POTENTIALS FOLLOWING CORTICAL STROKE IN THE RAT

52. Taylor, K.S. *; Anastakis, D.J.; Davis, K.D.
    Department of Surgery and Institute of Medical Science, University of Toronto, Toronto Western
    Research Institute, UHN
    FUNCTIONAL AND STRUCTURAL CORTICAL PLASTICITY FOLLOWING PERIPHERAL NERVE TRANSECTION

53. Titley, Heather K. 1*; Heskin-Sweezie,Raquel1;Broussard, Dianne M. 1,2,3
    1
     Department of Physiology, University of Toronto; 2Division of Fundamental Neurobiology, Toronto
    Western Research Institute, University Health Network; 3Faculty of Medicine, Division of Neurology,
    University of Toronto
    CONSOLIDATION AND DISRUPTION OF NEWLY FORMED MEMORIES IN THE VESTIBULO-OCULAR REFLEX
    DOES NOT DEPEND ON THE ROTATIONAL FREQUENCIES DURING LEARNING AND TESTING

                                                       - 10 -
54. Tsang, Eric W. *1,3; Hamani, Clement 2; Moro, Elena1; Mazzella, Filomena1; Poon Yu-Yan1; Lozano, Andres
    M2,3; Chen, Robert1,3
    1
     Divison of Neurology; 2Divison of Neurosurgery,University Heath Network, Toronto, ON, Canada;
    3
     Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    OSCILLATORY ACTIVITIES RECORDED FROM THE HUMAN PEDUNCULOPONTINE NUCLEUS REGION
    DURING VOLUNTARY MOVEMENTS

55. Weber, Alexander M*; Stanley, Elise F.
    Genetics and Development Division, Toronto Western Research Institute, University Health Network
    DETERMINING THE TRANSPORT RATE OF THE PRESYNAPTIC-TYPE CaV2.2 CALCIUM CHANNEL AT
    PHYSIOLOGICAL EXTERNAL Ca(2+) CONCENTRATIONS

56. Wheeler, Anne L.*1,2; Lerch, Jason P.3; Sled, John G.3; Frankland, Paul W.1,2,4
    1
     Institute of Medical Science, University of Toronto; 2Program in Neurosciences and Mental Health, The
    Hospital for Sick Children, Toronto; 3The Mouse Imaging Center, The Hospital for Sick Children, Toronto;
    4
     Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
    CHRONIC COCAINE DURING ADOLESCENCE PRODUCES STRUCTURAL ABNORMALITIES IN THE BRAINS OF
    MICE

57. Wong, Fiona K.*; Stanley, Elise F.
    Laboratory of Synaptic Transmission, Genes and Development, Toronto Western Research Institute,
    Toronto ON
    RAB3A INTERACTING MOLECULE (RIM) AND THE TETHERING OF PRESYNAPTIC TRANSMITTER RELEASE
    SITE-ASSOCIATED CAV2.2 CALCIUM CHANNELS

58. Yiu, Adelaide P. 1,2*; Cole, Christina J. 1,3; Neve, Rachael L4; Westaway, David 5; Josselyn, Sheena A. 1,2,3
    1
     Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto;2Institute of Medical
    Sciences, University of Toronto;3Department of Physiology, University of Toronto; 4Molecular
    Neurogenetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital,
    Belmont, MA, USA; 5Prion Centre, University of Alberta, Edmonton, AB
    MEMORY DEFICITS IN ALZHEIMER’S DISEASE: A POSSIBLE ROLE OF CREB?
59. Yong-Kee, Christopher J.*; Hanif, Asad; Nash, Joanne E;
    Department of Cell and Systems Biology , University of Toronto
    IDENTIFICATION OF CONVERGENT SUB-CELLULAR MECHANISMS INDUCED BY CELL STRESS DURING
    PARKINSON’S DISEASE

60. Zavalishina, L.1,2*; Safir, A.2; Yonekura, N.1 ; Logan, R. 1; Zhang, L.1, 3; Eubanks, J. 1,2,3
    1
     Division of Genetics and Development , Toronto Western Research Institute, Toronto; 2Department of
    Physiology; 3Institute of Medical Science, Surgery, Faculty of Medicine, University of Toronto.
    MBD2, ANOTHER METHYL-CPG-BINDING PROTEIN, CONTRIBUTES TO AUTISM-LIKE BEHAVIOURAL
    PHENOTYPE IN MICE

                                                         - 11 -
61. Zhang, W.-J.*1,2; Lau, A.1; Tymianski, M.1,2
    1
     Department of Fundamental Neurobiology, Toronto Western Research Institute, Toronto; 2Department
    of Physiology, Faculty of Medicine, University of Toronto
    PSD-95 INHIBITOR, TAT-NR2B9C, ATTENUATES BEHAVIOUR DEFICITS FOLLOWING TRAUMATIC BRAIN
    INJURY IN RATS

62. Zurek, A.A.1*; Saab, B.J.2,3 ; Orser, B.A.1
    1
     Departments of Physiology , Faculty of Medicine, University of Toronto; 2Samuel Lunenfeld Research
    Institute, Mount Sinai Hospital, Toronto; 3Department of Molecular Genetics, University of Toronto
    PERSISTENT MEMORY IMPAIRMENT FOLLOWING ISOFLURANE ANESTHESIA




                                                    - 12 -
   POSTER ABSTRACTS

1. Adusei, Daniel C.*; Pacey, Laura K.; Hampson, David R.
   Department of Pharmaceutical Sciences, University of Toronto
   DEVELOPMENTAL CHANGES IN GABAERGIC PROTEIN EXPRESSION IN FRAGILE X KNOCKOUT MICE
   Fragile X syndrome (FXS) is the most common heritable form of mental retardation. The disorder is
   caused by a trinucleotide repeat expansion in the 5’ UTR region of the Fmr1 gene, resulting in the loss of
   the Fragile X Mental Retardation Protein (FMRP). Recent evidence has suggested a role for GABAergic
   dysfunction in Fmr1 knockout mice. GABAA receptors are ligand-gated channels that are involved in
   several processes that are perturbed in FXS patients, such as controlling the excitability of the brain,
   modulating anxiety, cognition, memory and learning. However, previous studies in Fmr1 knockout mice
   have focused on expression at the mRNA level, while validation with protein expression studies has
   been comparatively limited. Furthermore, studies have only examined adult Fmr1 knockout mice for
   alterations in GABAergic transmission. Thus, it is possible that GABAergic alterations occur in Fmr1
   knockout mice during the critical periods of development when synaptogenesis and neuronal
   maturation occurs. To address this, we chose three time points (postnatal days 5, 12 and adulthood) to
   investigate the temporal expression of GABA receptor subunits, GABAergic metabolic enzymes, and
   proteins involved in GABA clustering and trafficking in Fmr1 knockout mice. Using quantitative western
   blotting analysis, we found that the GABAA receptor α1 subunit is down-regulated at postnatal days 5
   and 12; β2 subunit in down-regulated throughout development; and GABA transaminase is down-
   regulated at postnatal day 12. In addition, we found that glutamic acid decarboxylase is up-regulated in
   adult Fmr1 knockout mice. Our data demonstrate that alterations in GABA receptor expression are
   present in the CNS of Fmr1 knockout mice from the early postnatal period, suggesting that a greater
   understanding of the role GABAergic defects plays in fragile X knockout mice may lead to novel
   pharmacological interventions for FXS patients.




                                                     - 13 -
2. Agnihotri, Sabrina*1; Colantonio, Angela1,2,3; Polatajko, Helene1,2; Cameron, Deb1,2; Rumney, Peter4;
   Wiseman-Hakes, Catherine1,2; Bridger, Leslie; Keightley, Michelle L1,2,4
   1
    Graduate Department of Rehabilitation Science (University of Toronto), 2Department of Occupational
   Science and Occupational Therapy (University of Toronto), 3Toronto Rehabilitation Institute, 4Bloorview
   Kids Rehab
   EXPRESSIVE ARTS AS A SOCIAL AND COMMUNITY PARTICIPATION TOOL FOR ADOLESCENTS WITH
   ACQUIRED BRAIN INJURY
   BACKGROUND: Expressive arts therapy (EAT) has been shown to be useful for individuals who find
   meaningful verbal communication difficult. This is relevant to the adolescent population recovering
   from acquired brain injury (ABI) with regards to common difficulties in communication skills and
   disorganized speech. However, there is a lack of evidence connecting EAT directly to adolescents with
   ABI, especially with respect to improved social, emotional and community participation skills.
   OBJECTIVES: A pilot study was conducted to evaluate the feasibility of an expressive arts theatre skills
   training program for youth recovering from ABI. We also aimed to quantitatively capture pre-post
   improvements on a battery of measures evaluating social communication, emotional functioning and
   participation. METHODS: 4 adolescents between the ages of 13-16 with an ABI and identified social
   communication problems were recruited from Bloorview Kids Rehab’s NeuroRehabilitation Services-
   Outpatient and Inpatient programs. Participants took part in a camp experience, facilitated by theatre
   artists and occupational therapists, and engaged in various projects, such as mask work, character
   development and story-telling. A descriptive, multiple case-study analysis was carried out on
   quantitative measures administered 4 weeks prior, immediately prior and immediately after the camp.
   Outcome measures included the: (1) Canadian Occupational Performance Measure (COPM); (2) Goal
   Attainment Scaling; (3) Child and Adolescent Scale of Participation (CASP); (4) Profile of Pragmatic
   Impairment in Communication (PPIC); (6) Rosenberg Self-Esteem Scale; (7) Social Networks Inventory,
   and; (8) an emotional face labelling task. RESULTS: Initial analysis of the single-subject quantitative data
   revealed improvements in social and community participation goals as identified by Goal Attainment
   Scaling and COPM. Impairments in pragmatic communication behaviours also decreased in severity
   across the course of the program as measured by the PPIC. CONCLUSIONS: Preliminary results suggest
   that a combination of directed group activities and self-reflection within a creative learning context may
   improve social communication and participation for youth with ABI. The skills and knowledge gained by
   these youth will also be more adaptable to real life situations, as the program will allow the youth to
   form peer groups within the therapy to practice these new skills. The findings also suggest that more
   research is needed to develop improved measures of community participation for adolescents with ABI.




                                                      - 14 -
3. Ahmadi, Negar*1,2; Shapiro, Colin M1,2,3
   1
     Department of Cell and Systems Biology, University of Toronto, 2Toronto Western Research Institute,
   University Health Network, 3Department of Psychiatry, Faculty of Medicine, University of Toronto
   INVESTIGATION OF SLEEP IN CHRONIC TREATMENT-RESISTANT DEPRESSED PATIENTS
   Introduction: The existing literature supports a bi-directional relationship between sleep disorders and
   depression. Sleep disorders are often undiagnosed in the general population and in the psychiatric
   population. However, once detected treatment of sleep disorders among depressed patients has been
   shown to improve mood and alleviate depression. Among depressed patients, about 12-15% will remain
   chronically depressed and will not respond to treatment. The aim of this study was to investigate the
   sleep architecture and prevalence of sleep disorders among a group of chronic treatment-resistant
   depressed patients.
   Method: Twenty four patients who met diagnostic criteria for chronic treatment-resistant depression
   were recruited from local mood disorder clinics. Depression severity was assessed using the 21-item
   Hamilton Depression Scale (HAM-D) and clinical consultation. The patients underwent an overnight
   polysomnographic (PSG) study followed by Multiple Sleep Latency Test (MSLT).
   Results: Eighteen of the participants were females and the average age for the whole group was 45±9.6
   years. The average HAM-D score (± SD) was 26± 5. The average sleep onset latency and the average
   REM latency after sleep onset were 35±40 min and 380±89 min respectively (all patients were on
   antidepressants). The average sleep efficiency was 77±16%. The average slow wave was sleep
   percentage was 9±6% and the average REM sleep percentage was 12.2±6.8%. The average arousal
   index was 30±20/hr, the average Apnea-Hypopnea Index and the average Periodic Leg Movement Index
   were 10.9±17.6 and 13.4±18.2 respectively. Mean MSLT value was 9.4±3.9. Twenty one out of 24
   patients had an identifiable sleep disorder and eighteen had more than one sleep disorder. Twenty
   seven percent of patients had an undiagnosed moderate to severe sleep apnea and 24% of the patients
   had a moderate to severe periodic leg movement disorder. Eighteen percent of the patients were
   diagnosed with insomnia, 18% with excessive daytime sleepiness and 13% with fragmented sleep.
   Conclusion: The results suggest that chronic treatment-resistant depressed patients often have
   disturbed sleep architecture. A significant proportion of patients in this study had an undiagnosed sleep
   disorder that might have been the underlying cause or contributor to their chronic treatment-resistant
   depression.




                                                    - 15 -
4. Alves, Nyresa C.* 1; Bailey, Craig D.C. 1; Nashmi, Raad2; Lambe, Evelyn K.1
   1
     Department of Physiology, University of Toronto; 2Department of Biology, University of Victoria
   DEVELOPMENTAL SEX DIFFERENCES IN Α4Β2* NICOTINIC CURRENTS IN LAYER VI PYRAMIDAL NEURONS
   OF RODENT PREFRONTAL CORTEX
    There is a large sex difference in the prevalence of attention deficit disorder; yet, relatively little is
   known about sex differences in the development of prefrontal attention circuitry. Nicotinic receptors
   play a key trophic role in brain development, and developmental exposure to nicotine has been shown
   to increase vulnerability to attention deficit disorder. In male rats during development, nicotinic
   acetylcholine receptors excite a component of prefrontal attention circuitry, the corticothalamic
   neurons. These layer VI neurons play an important role in attention by gating the sensitivity of thalamic
   neurons to incoming stimuli. In this study, we have examined whether there are sex differences during
   development in the excitation of layer VI pyramidal neurons by nicotinic acetylcholine receptors. These
   experiments were conducted with whole cell recordings of neurons in brain slices of prefrontal cortex
   from mice and rats. Initial experiments used acetylcholine to stimulate nicotinic receptors in the
   presence of atropine to block muscarinic receptors, the other subtype of acetylcholine receptor. We
   found a prominent sex difference in the currents during the first postnatal month when female rodents
   had significantly smaller nicotinic currents in layer VI neurons in rats and two strains of mice (FVB and
   C57Bl/6) compared with age-matched males. Despite the sex difference in magnitude of the nicotinic
   currents during development, the properties of these currents were similar in males and females. In
   both sexes, the nicotinic currents were largely insensitive to action potential blockade, suggesting they
   were mediated directly by nicotinic receptors on the recorded neurons. In both males and females, the
   nicotinic currents were eliminated by DHβE, a competitive antagonist of the α4β2* subtype of nicotinic
   receptors. A physiological level of the drug nicotine elicited a small, but persistent, inward current in
   layer VI neurons from both sexes, again with a significant sex difference in magnitude. Since we
   observed a sex difference in the currents elicited by either nicotine or carbachol, agonists not broken
   down by endogenous acetylcholinesterase in the brain slice, we hypothesized that the density or
   expression pattern of nicotinic receptors in layer VI may be different in males and females during
   development. To address this question, we are examining a line of knock-in mice in which all α4-
   containing nicotinic receptors are labelled with YFP. Our electrophysiological recordings in these mice
   show prominent nicotinic currents in layer VI neurons during development with the same sex difference
   we have observed previously. In ongoing experiments, we are using multiphoton imaging of either the
   YFP alone or the YFP signal amplified with immunohistochemistry to examine and quantify the
   developmental sex differences. Further work is necessary to determine how the sex differences in
   nicotinic stimulation of prefrontal attention circuitry alters the development of prefrontal attention
   circuitry and whether the sex difference in nicotinic currents contributes to males’ vulnerability to
   attention deficit disorder.




                                                      - 16 -
5. Andre, Melanie*1,5,7; Anderson, Nicole D.3,4,5,7; Stuss, Donald T.1,3,4,6; Dawson, Deirdre R.1,2,5,7
   1
    Graduate Department of Rehabilitation Science, and Departments of 2Occupational Science &
   Occupational Therapy, 3Psychology, and 4Medicine, University of Toronto;
   5
    Kunin-Lunenfeld Applied Research Unit; 6The Rotman Research Institute, Baycrest; 7Toronto
   Rehabilitation Institute
   FURTHER EXPLORATION OF THE ECOLOGICAL VALIDITY OF TESTS OF EXECUTIVE FUNCTION
    Background: Traditional tests of executive function (EF) are infamous for having poor ecological validity.
    This often leads to a discrepancy between the test scores and everyday performance in the real-world.
    Patients may perform normally on tests of EF yet exhibit significant everyday dysfunction. Objective: To
    explore the ecological validity of commonly used EF tests in chronic acquired brain injury (ABI) patients
    (mean years post-injury = 11.49±7.94) by comparing performance on measures of EF to performance in
    daily life (as reported by an informant). Methods: Twenty-six (17 males, 9 females) participants with an
    ABI (12 traumatic brain injury, 14 stroke) and an informant for each took part in the study. Four
    traditional measures of EF were administered to the ABI participants 1) Wisconsin Card Sorting Test
    (WCST), 2) Trail Making Test Part B (TrailsB), 3) Digit Symbol (DS), and 4) Controlled Oral Word
    Association Test (COWAT). Two real-world measures were completed by the informants 1) Dysexecutive
    Questionnaire (DEX), and 2) Mayo-Portland Adaptability Inventory (MPAI). Results: Although modest
    correlations in the expected direction were found between 3 measures of EF (WCST, TrailsB and DS) and
    the total score on the MPAI (r=.30 to .36) and between 2 measures of EF (WCST and TrailsB) and the DEX
    (r=.29 and .30 respectively) only the WCST and the MPAI ability subscale were found to correlate
    significantly (r=.43, p=.03). Conclusions: Our current results suggest that standard measures of EF
    explain only modest amounts of variation in daily life performance in adults with chronic ABI. These
    results demonstrate the need for new, ecologically valid tests, specifically created for clinical use, in the
    field of cognitive rehabilitation.




                                                        - 17 -
6. Antflick, Jordan E.*1; Vetiska, Sandra1; Baizer, Joan S.2; Yao, Yi1; Baker , Glen B.3; David R. Hampson1,4
   1
    Leslie Dan Faculty of Pharmacy;2Department of Physiology and Biophysics, the University at Buffalo,
   Buffalo, New York; 3Neurochemical Research Unit and Bebensee Schizophrenia Research Unit, Dept. of
   Psychiatry, University of Alberta, Edmonton, Alberta, Canada;4Department of Pharmacology, University
   of Toronto, Toronto, Ontario, Canada,
   IS L-PHOSPHOSERINE A NEUROTRANSMITTER IN THE CENTRAL NERVOUS SYSTEM?
    L-serine-O-phosphate (L-SOP) is the immediate precursor to L-serine in the serine synthesis pathway and
    is also an agonist at the Group III metabotropic glutamate receptors (mGluRs). L-SOP is produced by the
    enzyme phosphoserine aminotransferase (PSAT) and metabolized to L-serine by phosphoserine
    phosphatase (PSP). Using a novel analytical procedure, we show that L-SOP is present in rat brain at
    about the same concentration (5 µM) as dopamine and that it is substantially more potent than L-
    glutamate at the mGluR4 receptor subtype. Immunocytochemical analyses showed that the
    distributions of PSAT and PSP in the cerebral cortex, hippocampus, and cerebellum were similar in the
    rat and macaque monkey brain. In the rat hippocampus, cells within the subgranular zone were co-
    labeled with anti-PSP and anti-PSA-NCAM, a marker for neurogenic cells. In the cerebellar cortex,
    Purkinje neurons expressed relatively high levels of both enzymes while robust expression of PSAT was
    also observed in the Bergmann glia. L-SOP released from Purkinje neurons or Bergmann glia could
    activate mGluR4 present on parallel fiber terminals. The presence of L-SOP in brain, its high potency at
    mGluR4, together with the restricted distributions of the synthetic and metabolic enzymes, suggest that
    L-SOP might act activate Group III metabotropic glutamate receptors in the CNS.




                                                      - 18 -
7. Arundine, A*1,2;Bradbury C1; Ruttan, L1; Green, REA1,2
   1
    Toronto Rehabilitation Institute, 2University of Toronto, Graduate Department of Rehabilitation Science
   EXAMINING LONG-TERM EFFICACY AND COMMUNITY INTEGRATION BENEFITS OF A COGNITIVE
   BEHAVIOUR THERAPY PROTOCOL ADAPTED FOR PEOPLE WITH BRAIN INJURY
   Background: We have previously demonstrated the efficacy of a cognitive behaviour therapy (CBT)
   protocol that was adapted to address the unique cognitive and emotional needs of ABI survivors, and
   which additionally includes a telehealth delivery modality (Bradbury et al, 2008). However, the
   maintenance of CBT treatment effects in ABI has yet to be investigated. The primary aim of the current
   study was to demonstrate that patients maintain benefits (reduction in psychological distress) after
   cessation of treatment over a 6-month duration in both conventional (group, face to face) and
   telephone administration modalities. Methods: Seventeen people with moderate to severe ABI (>1-year
   post injury) with elevated psychological distress were recruited. Participants received eleven sessions of
   CBT administered in either a face-to-face group format (G-CBT) or individually over the telephone (T-
   CBT). Post-treatment and follow-up performance on the Symptom Checklist-90-Revised (SCL-90-R), the
   Depression, Anxiety Stress Scales (DASS), the Community Integration Questionnaire (CIQ) and the Ways
   of Coping Questionnaire- Revised (WOC-R) was examined. Results: Psychological distress was
   significantly reduced from pre- to post-treatment and sustained at the 6- month follow-up period on
   both the DASS (t(15)=4.19, P<.01) and SCL-90-R (t(15)=6.32, P<.001) measures. Subgroup analyses
   revealed that both G-CBT and T-CBT modalities were similarly effective on the SCL-90-R. However, the
   G-CBT group showed greater symptom reduction than T-CBT when measured by the DASS.
   Discussion: CBT treatment effects were robust, and demonstrated maintenance of benefits 6- months
   post cessation of treatment. Findings regarding CBT treatment, coping and community integration are
   also discussed. To our knowledge, this is the first adapted psychological intervention demonstrating
   long-term efficacy for people with ABI.




                                                     - 19 -
8. Bae, James J.1,3*; Martinez-Canabal, Alonso2,4; Frankland, Paul.W. 1,2,4; Lu, Wei-Yang1-3
   1
    Department of Physiology; 2Institute of Medical Science, University of Toronto, Toronto, ON.;
   3
    Neuroscience Research, Clinical and Integrative Biology, Sunnybrook & Women's College Health
   Sciences Centre, Toronto, ON; 4Program in Neurosciences and Mental Health, Hospital for Sick Children,
   Toronto, ON.
   INCREASED EXPRESSION OF TRANSFORMING GROWTH FACTOR-β1 ALTERS SYNAPTIC STRUCTURE AND
   GLUTAMATE RECEPTOR EXPRESSION
   Transforming growth factor-beta 1 (TGF-β1) is a multifunctional injury-related cytokine that orchestrates
   key events of development, disease and repair. Secreted by both neurons and glial cells in the central
   nervous system (CNS), increased expression of TGF-β1 is associated with neurological diseases and brain
   trauma. To date, its role in the regulation of synaptic structures and transmission in the mammalian CNS
   remains unclear. To investigate the effects of chronic over-secretion of TGF-β1 on the structural and
   functional properties of neural cells, we used transgenic mice (T64) that over-express active form of
   TGF-β1 in hippocampal and cortical astrocytes. Immunohistochemical analysis demonstrated that in
   comparison with wild-type (WT) littermate controls, the number of cells in T64 mice expressing GFAP
   and CD11b increased significantly in the hippocampus and cortex. Notably, large immuno-clusters of
   synaptophysin and calbindin-D28K-positive immunoreactivity of neurons were, respectively, decreased
   in the CA3 region and the dentate gyrus through to the mossy fiber terminals. Decrease in calbindin-
   D28K and increase in GFAP protein levels in the T64 model were confirmed. Interestingly, protein levels
   of AMPA receptor subunits (GluR2 and GluR3, but not GluR4), and NMDA receptor subunits (NR1 and
   NR2A/B), were increased in the hippocampal and cortical region. Cultured primary astrocytes from T64
   mice show higher rate in proliferation and more elongated cell bodies and processes when compared
   with WT controls. To examine the effect of TGF-β1 alone in the regulation of neuronal functions, we
   cultured hippocampal neurons from WT rat embryos in the presence or absence of TGF-β1 (4.0 ng/ml, 7-
   12 days). Voltage-clamp recordings in these cultured neurons revealed that TGF-β1 significantly
   increased the amplitudes of voltage-gated K+ currents, Na+ currents and glutamate-induced currents
   (p<0.05) in treated cells. The observed increase in glutamate currents may be due, in part, to an up-
   regulation of ionotropic glutamate receptors, as shown through increased levels of AMPA receptors and
   NMDA receptors. Taken together, our results suggest that chronically increased expression of TGF-β1
   may activate glia and induce alterations in synaptic structures and glutamate receptor expressivity of
   surrounding neuronal populations. Further, TGF-β1 alone appears, at least in culture condition, to
   increase neuronal activity.




                                                    - 20 -
9. Buske, Christine*; Gerlai, Robert
   Cell & Systems Biology, Collaborative Program in Neuroscience
   TEMPORAL CHARACTERISTICS OF SHOALING BEHAVIOR OF ZEBRAFISH: LARGE SCALE DEVELOPMENTAL
   AND FINE RESOLUTION CHANGES.
   Vertebrate social behavior is complex and its mechanisms are not fully understood. Numerous human
   clinical conditions exist in which abnormal social behavior is the core symptom. Zebrafish are a highly
   social species, and given its practical features (small size, ease of maintenance) and its strong genetics, it
   appears to be a promising model organism for the analysis of the mechanisms of a number of complex
   behavioral phenomena including social behavior. Zebrafish is one of the most social vertebrate
   laboratory organisms. Zebrafish prefer their conspecifics and form shoals, i.e. aggregate in groups.
   Shoaling, however, is not well characterized in zebrafish. Before conducting a forward genetic
   (mutagenesis) study in zebrafish, we decided to characterize their shoaling both in the short time scale
   (shoal cohesion changes in the seconds range in the adult fish) and long time scale (shoal cohesion
   changes throughout development from day 0 post fertilization to day 90). Shoal cohesion was
   quantified by measuring the distance between all pairs of fish in a freely swimming group of ten subjects
   over the course of a six minute period. Measurements were obtained through the use of a custom
   software application developed in the laboratory. Analysis of the fine temporal resolution data revealed
   a consistent oscillation of group cohesion with an average frequency of 10 seconds and amplitude of
   approximately 2 body lengths. Analysis of shoal cohesion on the longer time scale was conducted on
   two separate sets of fish. The first set was followed longitudinally (measuring the same fish, a repeated
   measure design). The second set was analyzed cross-sectionally (testing fish belonging to different age
   groups at the same time, a between subject non-repeated measure design). In both sets we found a
   significant increase of shoal cohesion (as standardized to body length) with age. The increase of shoal
   cohesion was particularly fast between the developmental period 20-40 days post fertilization.
   Currently, we are designing behavioral tests that will allow us to quantify shoal cohesion changes
   induced by mutagens in an automated manner. We hope that these studies will facilitate the analysis of
   the biological and genetic mechanisms of vertebrate social behaviors and ultimately lead to the
   betterment of human mental health.




                                                       - 21 -
10. Chee, Justin*1; Tremblay, Luc2; Zabjek, Karl1
    1
     Graduate Department of Rehabilitation Science; 2.Faculty of Physical Education and Health
    THE EFFECT OF MECHANICAL AND SENSORIMOTOR PERTURBATIONS ON THE PHYSIOLOGICAL COST OF
    WALKING
   Introduction: The aim of the current study is to assess how oxygen consumption and the neural
   regulation of walking are influenced by immobilizing the ankle joint and vibrating the Achilles’ tendon in
   able-bodied young adults. While it has been established that patients who exhibit an increased centre of
   mass excursion during gait also increase their oxygen consumption to compensate for their abnormal
   gait pattern, it is unknown if this increase is due to purely mechanical or neurological reasons. In fact,
   there is a limited understanding of how proprioception interacts with the physiological cost of walking.
   Therefore, we predicted that introducing these mechanical and sensorimotor perturbations to the gait
   of able-bodied young adults would increase the energetic requirements of gait (i.e. VO2 and amplitude
   of trunk accelerations), with the combined application of both perturbations eliciting the largest rise in
   energetic cost. Methods: We used a cushioned air cast to minimize the range of motion of the ankle
   joint and a tendon vibrator to alter ankle proprioceptive feedback to induce mechanical and
   sensorimotor disturbances, respectively. Eleven able-bodied participants were instructed to walk around
   a circular track in a gymnasium at their normal, customary walking speed as follows: a) normally; b) with
   an air cast; c) with continuous Achilles' tendon vibration; and d) with both the air cast and tendon
   vibration concurrently. Throughout the protocol, oxygen consumption (VO2) was measured using the
   Cosmed K4b2 unit (Cosmed, Italy) and upper trunk accelerations using the Delsys Myomonitor IV
   Wireless Transmission and Datalogging System (Delsys, U.S.A.). Results: Initial analysis of the VO2 results
   from five individuals reveals that energy expenditure increases with air cast use and combined air cast
   and tendon vibration, but not with tendon vibration when applied independently. Similar trends are
   detected in vertical accelerations of the upper trunk of all eleven participants, displaying a decrease (2
   %) and increase (12 %) in upper trunk accelerations during the independent tendon vibration and air
   cast conditions respectively. However, the effect of the combined air cast and tendon vibration was less
   pronounced (11 %). Medio-lateral accelerations of the upper trunk do not yield any statistically
   significant changes. Conclusions: Overall, the effects of the mechanical and sensorimotor gait
   perturbations in this study are not mutually exclusive or simply additive in their effect on physiological
   cost, as initially surmised. Through further analysis of the relationship between range of motion and
   sensorimotor functions during normal gait, improvements to therapeutic interventions for individuals
   with gait deficits similar to those being invoked (e.g. ankle arthrodesis) may be revealed in the future.




                                                     - 22 -
11. Blankstein, Udi 1, 2*; Chen, Jerry 1, 2*; Mincic, Adina2; Davis Karen D.1, 2
    1
     Institute of Medical Science, University of Toronto; 2Division of Brain, Imaging and Behaviour – Systems
    Neuroscience, Toronto Western Research Institute, University Health Network, Toronto, Ontario,
    Canada, M5T 2S8
    * co-first authors (these authors contributed equally)
    NEUROANATOMICAL CORRELATES OF NEUROTICISM AND EXTRAVERSION IN HEALTHY ADOLESCENTS
    Objectives: Converging evidence from behavioural, psychological and functional brain imaging studies
    point to a link between specific personality traits (e.g., neuroticism, extraversion) and certain mental
    disorders (e.g., depression) and chronic pain states; suggesting that there may be a predisposition to
    these disorders. Furthermore, sex differences exist in the incidence of some psychiatric disorders and
    chronic pains. Recent studies in healthy adults and patient populations, suggest a relationship between
    personality traits and functional anatomy in cortical areas, including prefrontal regions. However, little
    is known about the neuro-maturational processes in the adolescent brain. Therefore, the aim of this
    study was to investigate the neuroanatomical correlates of neuroticism and extraversion in healthy male
    and female adolescents.Materials and Methods: Thirty-five right-handed healthy adolescents (20
    females, 15 males) aged 16-17 years old were recruited from the local population and consented to the
    study approved by the local research ethics board. Personality measures were assessed with the NEO-
    FFI prior to brain imaging. Subjects then underwent structural MRI scanning on a 3T GE scanner, 8
    channel phased array head coil. A T1-weighted 3D FSPGR anatomical scan (repetition time =11.8ms,
    echo time =5.2ms, flip angle 20º) acquired 120 1.5-mm-thick sagittal slices (FOV=24cm, 256 x 256
    matrix). Preprocessing and analysis of images was done using statistical parametric mapping software
    (SPM5; Wellcome Department of Imaging Neuroscience, Institute of Neurology, London, UK) in MATLAB
    7.0.1 (Mathworks, MA). Voxel based Morphometry (VBM) was implemented using tissue segmentation,
    normalization, 10mm FWHM smoothing, modulation and voxelwise multiple regression with an absolute
    threshold mask of 0.20 and total intracranial volumes entered as a covariate to control for between
    subject variance of gross brain size. The statistical threshold was set to p<0.001 with an extent of k>50
    voxels. Results: Neuroticism and extraversion scores were normally distributed and not significantly
    different between males and females (p = 0.24 and p = 0.11, respectively). The most prominent
    relationship between gray matter density and neuroticism was a negative correlation localized to the
    bilateral subgenual anterior cingulate cortex (ACC) (Brodmann area 25) in males only (t = 4.24).
    Interestingly, the left medial frontal gyrus/rostral ACC (Brodmann area 10/32) was found to be
    negatively correlated to extraversion in females (t = 4.19) but positively correlated in males (t = 4.32).
    Conclusion: These data reveal sex differences in the relationship between the personality traits of
    neuroticism and extraversion and gray matter density in cingulate and prefrontal cortical regions. These
    findings raise the issue of whether neuroanatomical correlates of personality traits are sustained over
    the lifespan. Future studies should assess whether such relationships represent a risk factor for chronic
    pains and mental disorders such as depression.




                                                      - 23 -
12. Chen, R.H.C.1*; Visanji N.2; Stanciu M.2; Mount H.T.J.1,2; Tandon A.2
    1
     Department of Physiology; 2Institute of Medical Science, Centre for Research in Neurodegenerative
    Diseases, Faculty of Medicine, University of Toronto, 6 Queen’s Park Crescent West, Toronto, Ontario,
    Canada, M5S 3H2.
    CHARACTERIZATION OF RAB3A AND Α-SYNUCLEIN INTERACTION AND CONSEQUENCES ON Α-SYNUCLEIN
    COMPARTMENTALIZATION
   The development of intracellular inclusions known as Lewy bodies is a histopathological hallmark of
   Parkinson’s disease (PD). The major component of these inclusions is α-synuclein, a protein that is
   predominantly localized to the pre-synaptic terminals of neurons. α-Synuclein appears to alternate
   between membrane-bound and cytosolic compartments. The dissociation of α-synuclein from vesicles
   is aided by brain cytosolic proteins that may play a role in the formation of neurotoxic fibrils under
   pathological conditions of oxidative stress. Previous work from our lab suggests that the small GTPase
   rab3a is involved in the binding of α-synuclein to synaptic membranes. In this study, we show that
   rab3a can be co-immunoprecipitated with α-synuclein in synaptosomes generated from murine brains
   and that this interaction appears to occur preferentially on vesicle membranes. Furthermore, we show
   that over-expression of the predominately GTP- and membrane-bound Q81L-rab3a mutant in
   depolarized SH-SY5Y human neuroblastoma cells causes a reduction of soluble compartment α-
   synuclein as compared to over-expression of wild-type rab3a. Our findings further the understanding of
   the dynamics in α-synuclein compartmentalization under non-pathological conditions.




                                                    - 24 -
13. Cumyn, Elizabeth M.*1,2; Yang, Jimau 1, Robinson, Brian H.3,4; Mount, Howard T. J.1,2,5
    1
     Centre for Research in Neurodegenerative Diseases; 2Institute of Medical Science; 3Dept. Biochemistry;
    4
     Hospital for Sick Children; 5Dept. Medicine (Div. Neurology)
    DISTINCT EFFECTS OF WILD-TYPE, A53T AND A30P α-SYNUCLEIN TRANSGENES ON BIOENERGETIC
    HOMEOSTASIS IN MOUSE BRAIN

   Parkinson’s disease (PD) is a synucleinopathy that affects 1% of the population. Familial PD can be
   caused by A53T and A30P point mutations in the α -synuclein gene that lead to protein misfolding and
   aggregation. Our lab has found progressive behavioural phenotypes and regional synaptic changes in the
   hippocampi, cortices and cerebella of transgenic (Tg) mice expressing human wild-type (WT) α-
   synuclein, or transgenes with A53T, A30P, or A53T+A30P (a double mutant, “DM” line) mutations.
   Mitochondrial dysfunction is well characterized in synucleinopathies and thus, we hypothesized that
   disruption of bioenergetic homeostasis may contribute to behavioural and neurochemical phenotypes
   of these mice. Mice aged 10 months and older were sacrificed by microwave fixation. Brain regions were
   dissected and levels of high energy phosphate donors were measured by HPLC with UV detection. A30P-
   Tgs had reduced levels of ATP in cortical areas (frontal and temporoparietal) as did DM-Tgs (frontal
   cortex only). Conversely, ATP was elevated in several areas of WT-Tg brain (cortex, hippocampus,
   cerebellum) and was unchanged in all areas of the A53T brain, except for hippocampus, where it was
   elevated. Creatine, a reservoir of intracellular ATP stores, was also elevated in both WT-Tg (cortex,
   hippocampus, cerebellum) and A53T-Tg (frontal cortex, hippocampus) brains. To determine whether
   creatine buffering might mask reductions in mitochondrial output, additional fresh brains were
   regionally dissected and bioenergetic enzyme activities were measured. Pyruvate dehydrogenase (PDH)
   activity can be decreased through phosphorylation by stress-activated protein kinase (SAPK). Previously,
   we found increased SAPK activation in the brains of mice expressing mutant α-synuclein Tgs. However,
   we found no relationship between constitutive SAPK activation and PDH activity. An exception was in
   the frontal cortex and cerebellum of DM-Tg animals, where high levels of phosphorylated SAPK
   coincided with reduced activity of PDH. Activity of mitochondrial complex I+III was reduced in frontal
   cortex of A30P-Tg and DM-Tg mice, but was elevated in the WT-Tg frontal cortex. Cortical complex I+III
   activity correlated directly with ATP alterations in this area. The A30P mutation, when present alone, or
   in combination with A53T, caused regional bioenergetic charge reduction that was consistent with the
   pattern of severe behavioural phenotypes in these lines. Conversely, the increased ATP and
   mitochondrial enzyme activity in WT-Tg mice was reflected in some significant improvements in their
   behavioural performance relative to non-Tg littermate mice. Our results reveal linkages between
   expression of mutant α-synuclein, bioenergetic dyshomeostasis, and behavioural impairment that
   precede gross histological evidence of brain cell loss.

   Supported by Parkinson Society Canada and NSERC.




                                                     - 25 -
14. DeSouza, Danielle*1,2; Mikulis, Dr. David3,4; Lerch, Dr. Jason5,6, Glazer, Joanna2; Green, Dr. Robin1,2
    1
     Graduate Department of Rehabilitation Science, University of Toronto; 2Toronto Rehabilitation
    Institute; 3Toronto Western Research Institute; 4Department of Medical Imaging, University of Toronto;
    5
     Department of Medical Biophysics, University of Toronto; 6Toronto Centre for Phenogenomics: MICe
    AN EXAMINATION OF THE BRAIN?S STABILITY FOLLOWING TRAUMATIC BRAIN INJURY USING MR-
    DERIVED VOLUMETRIC AND CORTICAL THICKNESS MEASURES: A LONGITUDINAL STUDY

   Background/Objectives: Magnetic resonance (MR)-based quantification tools have been shown to be
   useful and reliable measures for identifying in-vivo brain atrophy following moderate-severe traumatic
   brain injury (TBI). In particular, MR-based manual hippocampal volumetry and automated MR-derived
   measures of cortical thickness have been extensively used to illustrate longitudinal decreases in
   hippocampal volume and cortical thickness in numerous neuropathological populations. Although the
   literature provides evidence for progressive hippocampal volume loss in a subset of TBI patients from 5-
   months to approximately 24-months post-injury (Ng et al., 2008), it is not clear if this atrophy occurred
   earlier. Additionally, although automated cortical thickness analyses have been used in a number of
   neurodegenerative and psychiatric populations, to date, it has only been used in one TBI study
   conducted on a pediatric population (Merkley et al., 2008). Another gap in the literature concerns the
   risk factors for progressive atrophy, including injury etiology (fall vs. motor vehicle accident (MVA)), and
   injury severity (Glasgow Coma Scale (GCS) ratings). Thus, the objectives of the current study were to
   longitudinally examine a population of moderately-severely impaired TBI patients using MR-derived
   hippocampal volumetric and cortical thickness analyses to determine: 1) the time course for
   hippocampal atrophy; 2) a) cortical thickness changes post-trauma; b) the time-course for cortical
   thinning; 3) the relationship between hippocampal volume and cortical thickness changes; and 4) the
   influence of injury risk factors on grey matter outcomes.
   Materials/Methods: Twenty-three moderately-severely impaired TBI patients recruited from the
   Toronto Rehabilitation Institute acquired MRI scans on a Signa-Echospeed 1.5 Tesla high definition
   scanner at two time-points. The first scan was acquired approximately 5-months post injury, and the
   second scan acquired either: a) within the first year of injury (mean, 8± 2.6 months), or b) approximately
   24-months post injury (mean, 26.1± 7.5 months). Scans at both time-points underwent manual
   hippocampal volumetric analyses (DISPLAY), in addition to automated cortical thickness analyses (ASP).
   Prior to analyses both pre-processing and quality controls steps were taken to ensure comparability and
   integrity of scans. Percent annual change scores were computed separately for each group.
   Preliminary Results (hippocampal volumetric data only): Comparisons for left and right (n=22)
   hippocampi using annual percent change scores for the two groups showed a statistically significant
   difference between patients with follow-up scans taken within the first year of injury, as compared to
   patients who had scans taken approximately 24-months post-injury (P<.01). Further analyses
   determined these atrophic changes were significant for the right (P<.01), but not the left (P=.263)
   hippocampi. Risk factors for progressive atrophy (n=17), including injury etiology and injury severity did
   not significantly differ in their affect on left (P=.290; P=.489), or right (P=.640; P=.470) annual percent
   hippocampal change scores.
   Discussion: These data provide novel evidence for the time course of progressive hippocampal atrophy
   following moderate-severe TBI, with the majority of atrophy occurring within the first year of injury. The

                                                      - 26 -
right hippocampi, in particular, demonstrated significantly marked atrophy within the first year. Neither
injury etiology nor injury severity impacted the degree of hippocampal atrophy in this sample, which
could partly be attributable to the smaller sample size used for these analyses. Determining the time-
course for atrophic grey matter changes and potential risk factors for progressive atrophy will aid in
providing further insight into long-term TBI outcome. Note: Cortical thickness data are currently being
analyzed.




                                                  - 27 -
15. Elbert, Adrienne*; Gomez, Lissette; Cate-Carter, Tasha; Wigg, Karen; Feng, Yu; Archibald, Jennifer;
    Anderson, Barbara; Kerr, Elizabeth; Lovett, Maureen; Humphries, Tom; Barr, Cathy
    University of Toronto: Institute of Medicine and Department of Psychiatry
    READING DISABILITIES: ROLE OF POLYMORPHISMS IN CANDIDATE GENES ON CHROMOSOME 6P
    Reading Disabilities (RD) affect 3-6% of school-aged children, often resulting in academic impairment.
    Markers in neuronal genes KIAA0319 (6p) and DCDC2 (6p) show association with RD. However, it is
    unclear which or if both of these genes are involved in RD etiology, as both have been supported, but in
    different samples. Moreover, the functional changes contributing to RD susceptibility in these genes are
    unknown. The purpose of this study was to investigate potential, functionally-relevant polymorphisms in
    the protein-coding and regulatory sequences of these genes. The selected polymorphisms in KIAA0319
    were genotyped and analyzed for association to RD by Transmission/Disequilibrium Test (TDT).
    Haplotypes were analyzed using Haploview. The results of the haplotype analysis for polymorphisms in
    KIAA0319 showed support for a haplotype associated with RD (p=0.021). Specifically, preliminary results
    suggest that longer alleles of a human-specific microsatellite (JA04) may contribute to our risk haplotype
    in KIAA0319. The selected polymorphisms in DCDC2 were also genotyped and analyzed for association
    to RD by TDT. Results showed no biased transmission of DCDC2 alleles in RD. Previous findings from our
    lab suggested DCDC2 may be associated with ADHD. Therefore, DCDC2 polymorphisms were genotyped
    in our ADHD sample. Results showed a trend for association of DCDC2 markers with ADHD.




                                                      - 28 -
16. Farb, Norman*1; Anderson, Adam1; Segal, Zindel2
    1
     Department of Psychology, University of Toronto; 2Centre for Addiction and Mental Health, University
    of Toronto
    LETTING GO OF SADNESS: MINDFUL DETACHMENT IN EMOTION REGULATION
   Effectively regulating negative emotion is important for mental health. Indeed, extant research suggests
   that emotional reactivity to stressors predicts negative health outcomes. Mindfulness training (MT) has
   been shown to reduce the risk of depressive relapse and improve chronic mood, but little is known
   about its mechanisms of action. Using fMRI, the authors have developed a model of mindful emotion
   regulation linking: i) neural indices of depressive relapse risk, and ii) neural and subjective changes in
   emotional reactivity associated with MT. Evidence from two fMRI studies will be presented to support a
   model of MT promoting reduced emotional reactivity to dysphoric challenge. The idea of reduced
   reactivity will be explored in Study 1, investigating neural indices of emotional reactivity that predict
   relapse and recovery in a population at high risk for depressive relapse. Study 2 presents the association
   between mindfulness training (MT) and neural markers of emotion reactivity, in which MT was not
   associated with altered subjective experience of sadness following dysphoric challenge, but was
   associated with reduced neural reactivity. The poster presentation will attempt to link MT-related
   changes in interoceptive processing with neural indices of reduced risk for depressive relapse. Taken
   together, the studies suggest that neural changes associated with mindfulness training may facilitate a
   reduction in maladaptive emotional reactivity through enhanced access to interoceptive information. A
   comparison of the neural signatures predicting depressive relapse and areas associated with
   mindfulness training will be discussed.




                                                     - 29 -
17. Fenili, Daniela*; McLaurin, JoAnne
    Centre for Research in Neurodegenerative Diseases, Department of Laboratory Medicine and
    Pathobiology, Collaborative Program in Neuroscience, University of Toronto
    CHARACTERIZATION OF INOSITOL TRANSPORTERS AS A METHOD FOR DRUG DELIVERY TO THE CNS
   One challenge to designing drugs for targeting CNS diseases is to develop compounds that when given
   orally, cross the blood-brain barrier to reach their target sites in the brain. One design strategy is to
   develop drugs that can cross into the brain using a known transport system. myo-Inositol is able to
   cross into the brain using the inositol transporters, of which there are three: one hydrogen/myo-inositol
   cotransporter (HMIT) and two sodium/myo-inositol cotransporters (SMIT1, SMIT2). Our laboratory has
   previously shown that scyllo-inositol is able to both prevent and reverse Alzheimer’s disease pathology
   in the TgCRND8 mouse model of Alzheimer’s disease. We have also shown, using gas
   chromatography/mass spectrometry, that ad libitum treatment of mice with scyllo-inositol results in a
   significant increase in the brain levels of scyllo-inositol in both TgCRND8 and non-Tg littermates (Fenili et
   al, 2007, J Mol Med). Competitive transport assays have been developed to examine the minimal
   binding requirements for transport by the three known inositol transporters in astrocytic and neural cell
   lines. Inositol, simple sugars and related compounds, 20 in total, were used to define the structural
   features required for active transport. Further the relative expression of the transporters as a function
   of age and disease progression was analyzed in the cortex, hippocampus, septum and cerebellum using
   QPCR. Across all brain regions analyzed the expression level of the transporters were HMIT > SMIT1 >
   SMIT2. This result did not vary with age or disease phenotype.




                                                      - 30 -
18. Gardezi, Sabiha; Li, Qi; Stanley, Elise F.
    Genetics and Development Division, Toronto Western Research Institute, University Health Network,
    N-TYPE CALCIUM CHANNEL DOES NOT INTERACT DIRECTLY WITH PDLIM5
   PDLIM5 (PDz, Lin-11, Isl-1, Mec-3) is of current interest as a possible risk factor for several severe
   psychiatric mood disorders such as schizophrenia and depression. The protein has an N-terminus PDZ
   domain and three consecutive C-terminus LIM domains and has been localized to presynaptic terminals
   in the CNS, raising the possibility that it plays a role in transmitter release. A recent paper concluded
   that PDLIM5 enhances modulation of the presynaptic-type calcium channel, Cav2.2 by PKCε, serving as
   an adaptor to link these two proteins (Maeno-Hikichi et al., Nat Neurosci 6:468, 2003). OBJECTIVE: We
   set out to test the hypothesis that PDLIM5 is part of a complex with Cav2.2 at the presynaptic nerve
   terminal. MATERIALS AND METHODS: Specific antibodies were used to identify Cav2.2 (rat polyclonal
   Ab571) and PDLIM5 (mouse polyclonal PDLIM5pM) for both immunocytochemical and biochemical
   analyses. The calyx-type presynaptic terminal of the chick ciliary ganglion, at which virtually all the
   channels are Cav2.2 type, was used for quantitative immunocytochemistry (ICA/ICQ method; Li et al., J
   Neurosci 24:4074, 2004) to test for a presynaptic Cav2.2/PDLIM5 protein complex in situ while various
   rat brain (RB) fractions including purified synaptosome lysate were used for biochemical analyses.
   RESULTS: Immunostaining confirmed the presence of PDLIM5 at the giant calyx-type presynaptic
   terminal of the chick ciliary ganglion but there was very little obvious co-localization. We concluded
   from quantitative staining intensity analysis that PDLIM5 and Cav2.2 proteins do not covary at the calyx
   nerve terminal, as would be expected for a common protein complex. Further, we did not observe co-
   immunoprecipitation of PDLIM5 and Cav2.2 from whole brain, crude brain membrane, or purified
   synaptosome lysates. CONCLUSION: We conclude that native PDLIM5 is not part of a common molecular
   complex with Cav2.2 at the presynaptic terminal, arguing against the Cav2.2-PDLIM5-PKCε tripartite
   protein complex hypothesis.

   (This study was funded by the Canadian Institute for Health)




                                                     - 31 -
19. Gauster, Andrea*; Yunusova, Yana
    Department of Speech-Language Pathology, University of Toronto
    EFFECT OF SPEAKING RATE ON MEASURES OF VELOPHARYNGEAL FUNCTION
   We studied the effect of speaking rate on aerodynamic and acoustic measurements of velopharyngeal
   (VP) function in 29 adult speakers (14m, 15f) with no known pathology. The aim of this study was to
   provide normative data on the effect of speaking rate on VP function, but also to provide information
   which may be useful for the analysis of speech in conditions which may alter one’s speaking rate such as
   Amyotrophic Lateral Sclerosis (ALS). The pressure-flow method was used to collect aerodynamic data
   during the nasal-plosive sequence /mp/ in the word “hamper”, the /m/ in “made” during the utterance
   “mama made some lemon jam”, and the first /p/ in “puppy” during the utterance “buy Bobby a puppy”.
   A Nasometer was used to collect nasalance scores for the entirety of these utterances. Values for these
   measures were collected under four speaking rate conditions (normal, fast, slow, and slowest). We
   hypothesized that speaking rate would affect VP orifice area, nasal airflow rate, and nasalance, but not
   intraoral pressure. Results indicated that nasal airflow and VP orifice area were unaffected by speaking
   rate whereas intraoral pressure tended to decrease as speaking rate slowed. Nasalance was greater for
   BBP at slow speaking rates and nasalance distance (MMJ – BBP) decreased at slow rates. The data was
   interpreted with respect to expectations set forward in the literature on normal and disordered speech
   motor control.




                                                    - 32 -
20. Goodfellow, Nathalie M.1; Benekareddy, Madhurima2; Vaidya Vidita A.2; Lambe, Evelyn K.1,3
    1
     Department of Physiology, University of Toronto, Toronto Ontario Canada; 2Department of Biological
    Sciences, Tata Institute of Fundamental Research, Mumbai, India; 3Department of Obstetrics and
    Gynaecology, University of Toronto.
    LAYER II/III OF THE PREFRONTAL CORTEX: INHIBITION BY THE SEROTONIN 5-HT1A RECEPTOR IN
    DEVELOPMENT AND STRESS
   The modulation of the prefrontal cortex by the neurotransmitter serotonin (5-HT) is thought to play a
   key role in determining adult anxiety levels. Layer II/III of the prefrontal cortex, which mediates
   communication across cortical regions, displays high levels of the 5-HT1A receptor in normal individuals
   and significantly lower levels in patients with anxiety disorders. Here, we examine how serotonin
   modulates pyramidal neurons in layer II/III of the rat prefrontal cortex throughout postnatal
   development and in adulthood. Using whole cell recordings in brain slices of rat medial prefrontal
   cortex, we observed that serotonin directly inhibits layer II/III pyramidal neurons through 5-HT1A
   receptors across postnatal development (P6 to P96). In adulthood, a sex difference in these 5-HT1A
   currents emerges, consistent with human imaging studies of 5-HT1A receptor binding. We examined the
   effects of early life stress on the 5-HT1A receptor currents in layer II/III of prefrontal cortex. Surprisingly,
   animals subjected to early life stress displayed significantly larger 5-HT1A-mediated outward currents
   throughout the third and fourth postnatal weeks and increased 5-HT1A receptor mRNA during the
   second postnatal week. Subsequent exposure to social isolation in adulthood resulted in almost
   complete elimination of 5-HT1A currents in layer II/III neurons suggesting an interaction between early
   life events and adult experiences. These data represent the first examination of functional 5-HT1A
   receptors in layer II/III of the prefrontal cortex during normal development as well as after stress.
   Further research in this layer is essential to understand how development of the prefrontal cortex
   contributes to anxiety responses in adulthood.

   (This research was supported by an NSERC Discovery Grant (EKL), the Canadian Foundation for
   Innovation (EKL), and the Canada Research Chairs program (EKL). NMG was supported by a Margaret
   Santalo fellowship)




                                                        - 33 -
21. Grieder, Taryn *; Sellings, Laurie H.; -Kee, Ryan Ting-A; van der Kooy, Derek
    Institute of Medical Science, University of Toronto, Canada.
    DOPAMINERGIC SIGNALING MEDIATES NICOTINE DEPENDENT WITHDRAWAL AVERSIONS BUT NOT THE
    MOTIVATIONAL EFFECTS OF ACUTE NICOTINE WITHDRAWAL.
    Nicotine is the major reinforcing constituent of tobacco smoke that is responsible for the smoking habit
   in humans. The mesolimbic dopamine (DA) system is implicated in the processing of nicotine’s acute
   motivational properties, although the role for DA signaling in dependent and withdrawn animals has
   been less well studied. The opponent process theory of motivation predicts that a motivational stimulus
   will trigger an initial first process followed by a rebound second process in the opposite direction.
   Withdrawal from chronic nicotine can be viewed as the secondary opponent process caused by the
   presence of nicotine in a dependent animal. We examined the opponent processes of acute and chronic
   nicotine and the involvement of DA signaling in these processes, using a modified place conditioning
   paradigm, the BNW procedure. We report that nicotine dependent rodents avoid a withdrawal-paired
   environment and that these nicotine withdrawal aversions were blocked by the administration of the DA
   receptor antagonist α-flupenthixol prior to conditioning. Furthermore, the conditioned withdrawal
   aversions seen in wild-type nicotine dependent mice were blocked in D2 receptor knockout mice.
   Conversely, in previously naive animals, α-flupenthixol treatment attenuated the initial aversive
   motivational process, while having no effect on the motivational response to acute nicotine withdrawal.
   These results suggest that DA signaling is necessary for the opponent second process in nicotine
   dependent and withdrawn rodents, but not the secondary motivational process in naive animals.
   Further, signaling at the dopamine D2 receptor is critical in mediating withdrawal aversions in nicotine
   dependent animals. We propose that the alleviation of nicotine withdrawal may be primarily driving
   nicotine motivation in dependent animals.




                                                    - 34 -
22. Hammad, Sherief* ;Kennedy, John M.
    Department of Life Science, University of Toronto at Scarborough, Toronto, ON
    ANGLE ILLUSION WITH CONVERGENCE AND NO FORESHORTENING
   In perspective pictures showing cubes and cylinders, shapes on the picture surface may be misperceived
   (Hammad et al. 2008a, b). Perspective pictures use convergence and foreshortening, but foreshortening
   alone is sufficient to create the misperception (Hammad & Kennedy, in prep). Is convergence sufficient?
   Here, our stimuli were projections of irregular pyramids, each with a square top, projected in the picture
   as a quadrilateral with acute and obtuse angles. Since the pyramids were irregular and varied, there was
   no information across the stimuli for constant but foreshortened sides. At different tilts of the square,
   observers estimated an acute angle in the quadrilateral it projected. The angles were overestimated
   towards 90 degrees, with the maximum error at intermediate tilts (about 40 degrees projected angle).
   Hence, to produce the misperception, foreshortening of a constant, regular pyramid’s sides is not
   required. We argue foreshortening and convergence information for 3-D work independently, each
   affirming the other. They offer 3-D information, and the information creates illusions on picture
   surfaces. Multiple sources of information may simply generate, affirm and reinforce a constant-strength
   illusion.




                                                     - 35 -
23. Ho, Ernest C. Y. 1,2*; Zhang, Liang2,3; Skinner, Frances K. 1,2,3,4
    1
     Department of Physiology; 2Toronto Western Research Institute, University Health Network;
    3
     Department of Medicine (Neurology); 4Institute of Biomaterials and Biomedical Engineering, University
    of Toronto.
    MATHEMATICAL ANALYSES AND SIMULATIONS GIVE RISE TO A NOVEL HYPOTHESIS FOR THE
    EMERGENCE OF SLOW POPULATION RHYTHMS
   Inhibitory, interneuronal networks are known to underlie high frequency gamma (40-80 Hz) population
   activities in several brain regions including hippocampus. Network mechanisms involve the fast,
   inhibitory GABAA receptor decay time constant (5-10ms) individual interneurons are able to synchronize
   each other and sustain high frequency population activities. Interneuronal networks are also known to
   underlie low frequency population rhythms 0.5-4 Hz spontaneous in vitro rhythms in hippocampus [1]
   that likely constitute part of the in vivo activities that occur during slow wave sleep. As such, it is
   important to understand how these slow rhythms emerge. However, it is unclear how the same
   interneuronal network system can give rise to slow populations rhythms in the absence of an explicit
   slow timescale. Here we show, via simulations of 20-cell interneuronal network models, that suitable
   synaptic background activities (SBAs) consisting of excitatory and inhibitory synaptic conductances can
   yield slow rhythms even in the absence of any explicit slow timescale. The model parameter values
   needed to give rise to the slow population rhythms are obtained by mathematically analyzing a reduced
   low-dimensional mean field theory model. Thus, we hypothesize that slow population oscillations can
   emerge in interneuronal networks with appropriate SBAs in the absence of any explicit slow
   parameters. In previous work we have quantified SBAs from in vitro experiments exhibiting slow
   oscillations [2]. Using our extracted SBAs on larger, more realistic mathematical interneuronal network
   models we can directly link our mathematical models with experiment and test our hypothesis. If slow
   population oscillations do occur in these simulations, then it strongly suggests that the balance of
   excitatory and inhibitory synaptic conductances in the SBAs is critical for the production of slow
   population rhythms.

   [1] Wu et al: J Neurophysiol 93:2302-2317.(?2005?)
   [2] Ho et al: Hippocampus 19(2)?:152-165.(2009)




                                                     - 36 -
24. Huang, Lili*; Kanungo, Anish K.; Henderson, Jeffrey T.
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario,
    Canada.
    THE ROLE OF SMAC/DIABLO IN REGULATING PROGRAMMED CELL DEATH OF MOTOR NEURONS AND
    SYMPATHETIC NEURONS
   Programmed cell death (PCD) is a highly conserved process of cellular suicide that is required for the
   proper development and homeostasis of eukaryotic organisms. During development, motor neurons of
   the central nervous system (CNS) and sympathetic neurons of the superior cervical ganglion (SCG,
   peripheral nervous system; PNS) are generated in excess numbers and compete for a limited supply of
   target-derived trophic support. Those neurons which fail to innervate their peripheral targets are
   removed via PCD during late embryonic/early postnatal development. The terminal stages of PCD
   involve the activation of a subgroup of the caspase family of cysteine proteases, termed the executioner
   caspases (caspase-3, -6, and –7). Previous work in our laboratory has demonstrated that caspase-3 is
   required for developmental and injury-induced PCD of sympathetic neurons but not motor neurons in
   vivo. Members of the inhibitor of apoptosis protein (IAP) family, such as XIAP, act to thwart the
   proteolytic activity of caspase-3. IAPs are themselves regulated by Smac/DIABLO, a pro-apoptotic
   protein released from the mitochondria upon the induction of PCD. Previous efforts to characterize the
   role of Smac/DIABLO have demonstrated that this factor is largely dispensable with respect to PCD in
   proliferating cells, however, its role in neurons remains unclear. In the present study, we have examined
   Smac null mice to determine the role of Smac/DIABLO in regulating two forms of neuronal PCD in vivo:
   (i) axotomy–induced PCD of motor neurons, and (ii) developmental PCD of sympathetic neurons. Our
   data demonstrates that the deletion of Smac/DIABLO does not significantly enhance motor neuron
   survival following early postnatal axotomy. However, deletion of Smac/DIABLO resulted in a 35.6%
   reduction (smac (+/-), n = 9; smac (-/-), n = 7; p < 0.01) in the number of sympathetic neurons within the
   SCG at postnatal day 10. In concert with these findings we also find that terminal adrenergic axonal
   innervation by SCG neurons within the ear pinna is significantly lower in Smac null mice as opposed to
   controls. These results are in contrast to the known pro-apoptotic function of Smac/DIABLO, and
   suggest that Smac/DIABLO may interact in other signaling pathways that promote the proper
   development and/or homeostasis of SCG neurons in vivo. Efforts are currently underway to determine
   the contribution of Smac/DIABLO in mediating injury-induced PCD of SCG neurons in vitro and to
   uncover the mechanism underlying the loss of SCG neurons in Smac null mice.




                                                     - 37 -
25. Hui, Kelvin K.W.*1; Liadis, Nicole2; Robertson, Jennifer3; Kanungo, Anish1; Henderson,
    Jeffrey T.1
    1
     Department of Pharmaceutical Sciences, University of Toronto; 2Department of Medical Biophysics,
    Faculty of Medicine, University of Toronto; 3Department of Pathology and Molecular Medicine, Faculty
    of Health Sciences, McMaster University
    MOLECULAR MECHANISM OF NEUROPROTECTION MEDIATED BY IMMUNOPHILIN LIGANDS
   Immunophilin ligands such as cyclosporin A (CsA) and FK-506 have been traditionally used in clinical
   practice for immunosuppression. Studies over the past 15 years have demonstrated that they also
   possess both neuroprotective and neurotrophic properties. While cyclophilins and FK-506 binding
   proteins (FKBPs), respectively, have been identified as principal cellular targets for these agents, the
   mechanisms behind their neuroprotective properties remain controversial. Using an axotomy-induced
   motor neuron injury model, we have previously demonstrated that CsA and FK-506 enhanced neonatal
   facial motor neuron survival following injury (27% and 40% motor neuron survival, respectively, as
   compared to 15-16% in vehicle-treated groups). To determine the molecular mechanisms of these
   effects, we have examined several signal transduction pathways relevant to this process. In the present
   study, we have utilized pharmacologic inhibitors of these pathways, cypermethrin (cyclophilin/FKBP-
   independent calcineurin inhibition), rapamycin (FKBP-dependent calcineurin-independent pathway),
   and 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) (cyclophilin/FKBP-dependent HSP-90
   inhibition), for their ability to mediate neuroprotection following injury. Facial nerve axotomy was
   performed at postnatal day 3, followed by daily administration of the above inhibitors until the time of
   sacrifice at 7 days post-injury. Total facial motor counts were subsequently performed to assess the
   ability of these agents to promote neuroprotection. Interestingly, of these only cypermethrin was
   observed to enhance motor neuron survival following axotomy (cypermethrin versus vehicle: 32% and
   12%; rapaymycin versus vehicle: 17 and 13%; 17-AAG versus vehicle: 22% and 25% - examined at 4 days
   post-injury), suggesting that calcineurin inhibition plays a direct role in mediating neuroprotection. In
   addition, we have further demonstrated that inhibition of calcineurin functionally alters PCD signaling by
   maintaining the phosphorylation status of Bcl-2 family protein Bad. The results suggest that calcineurin
   inhibition plays a key role in regulating neuroprotection, but not the neurotrophic properties of
   immunophilin ligands such as CsA and FK-506; and supports a model in which neuroprotective and
   neurotrophic effects of these agents are elicited via distinct pathways.




                                                     - 38 -
26. Hui, Kwokyin*; Fernandes, Abigail; Luu, Michael; Lan, Freeman; Feng, Zhong-Ping
     Department of Physiology, University of Toronto.
    INSIGHTS INTO REAL-TIME PCR: A METHOD TO IDENTIFY TREATMENT EFFECTS AND OUTLIERS
   Real-time PCR, or qPCR, is a highly-sensitive technique used to determine the quantity of gene in a
   sample which may contain many other genes. In conjunction with reverse-transcription (RT) of mRNA,
   the method has been used extensively to determine the expression levels of specific genes in tissue/cell
   samples and determine whether or not certain treatments or conditions can alter the expression of
   these genes. However, RT-qPCR is not without inherent technical problems. First, the efficiency of the
   replication process has a major impact on the quantitative estimates of the expression levels. Second,
   the cycle-threshold output from qPCR must be calibrated to correlate them with gene expression levels.
   Third, the expression must be normalized to account for sample-sample variances in quantity of
   tissue/cells. The use of a standard-curve is usually used to resolve the first two issues, but can only be
   used in a limited range of data. For the third issue, normalization against a house-keeping gene, such as
    -actin, is very common but assumes that this gene is not affected by the treatment/condition. In the
   current study, we examined RT-qPCR data from NGF-treated PC12 cells. We present a method that can
   be used to identify (1) genes affected by the treatment and (2) outliers.




                                                     - 39 -
27. Kim, Hyunhee*; Wong, Fiona F.*; Stanley, Elise F.
    Dept. of Physiology
    CHOLINERGIC TRANSMISSION FROM SCHWANN CELLS ONTO DRG NEURON SOMATA
   Dorsal root ganglion somas are known to be surrounded by an enveloping Schwann cell. Previous
   published results indicate that the Schwann cells express P2X receptors and are can be depolarized by
   ATP secreted from the neuron (1). We have investigated the possibility that these Schwann cell also
   communicate with the DRG neuron by chemical synaptic transmission.
   Electron microscopy confirmed the presence of Schwann cells that envelop chick DRG neurons in situ.
   These ganglia were subjected to gentle enzymatic dissociation to isolate the soma together with their
   attached Schwann cells. We then recorded from the neurons by standard patch clamp in the whole-cell
   configuration. While holding the membrane potential at -80 mV we detected numerous small inward
   current transients that were identified as miniature excitatory postsynaptic currents (mEPC). We tested
   for the neurotransmitter type with standard blocking agents for glutamate (NBQX), ATP/P2X (suramin),
   and ACh (d-tubocurarine). Only d-tubocurarine significantly reduced the mEPC amplitudes, identifying
   the transmission as cholinergic. We next applied ATP onto the Schwann cell to test for evoked
   secretion. After a 10-15 second latency the ATP treatment caused a marked increase in mEPC frequency
   and this effect was abolished by d-tubocurarine.
   Our results indicate that Schwann cells can excite the enveloped DRG neurons and suggest that there is
   a two-way communication between these cell pairs. These results may be important for the control of
   DRG neuron firing rates and hence, sensory perception.

   Zhang X, Chen Y, Wang C, Huang LY (2007) Neuronal somatic ATP release triggers neuron-satellite glial
   cell communication in dorsal root ganglia. Proc Natl Acad Sci USA 104:9864–9869.




                                                    - 40 -
28. Janus Monika*; Lewis, Marc
    Department of Human Development and Applied Psychology, OISE/UT
    ERP RESPONSE ASSOCIATED WITH EMOTION REGULATION ON A GO/NO-GO TASK IN NORMAL CHILDREN
   Background: Emotion regulation is a critical component of healthy development, yet studies have only
   recently begun to focus on neural correlates of emotion regulation in children. Electrophysiological
   measures of scalp EEG allow us to extract the N2 event-related component, considered a marker of
   emotion regulation and prefrontally-mediated attention and inhibitory control. A decrease in frontal N2
   amplitude and latency has been shown as cortical efficiency increases. Hypothesis: We hypothesized
   that children who score high on measures of inattention and low on inhibitory control exhibit greater N2
   latencies, as potential indicators of delayed cortical control and deficient emotion regulation. Methods:
   Non-invasive electroencephalography (EEG) was used to record neural activity in normal children aged
   7-17 years old (n=80) while engaged in a go/no-go task. The frontal N2 was detected 200-400ms post-
   stimulus and measured when participants correctly inhibited a prepotent response (correct no-go trials).
   The extracted N2 was correlated with measures of temperament, reported by the participants’ parents
   using The Early Adolescent Temperament Questionnaire (EAT-Q). Results: As predicted, greater N2
   latencies were shown to be associated with higher measures of inattention and greater difficulty with
   inhibitory control (p < 0.05). Conclusion: These findings suggest that the N2 component may be
   associated with cortical processing involved in attention and inhibitory control, central aspects of
   emotion regulation in normal children.




                                                     - 41 -
29. Kirshenbaum, Greer*; Duffy ,Steven; Roder, John
    Institute of Medical Science and Program in Neuroscience
    MUTATIONS IN THE ALPHA-3 SODIUM POTASSIUM PUMP UNDERLIE A MOUSE MODEL OF BIPOLAR
    DISORDER
   The nonexistence of a valid animal model for Bipolar disorder (BD) has been hindering the discovery of
   the underlying neurobiology of the disease and the development of novel treatments. By ENU
   mutagenesis, my lab has created a mouse called Myshkin that has a point mutation in the alpha-3
   sodium potassium ATPase pump (ATP1A3) causing haploinsufficiency. Myshkin is a compelling new
   mouse model of BD as it demonstrates construct validity, face validity and predictive validity. The model
   has construct validity as the underlying pathology of BD may involve altered Na/K ATPase activity.
   Neurons of BD patients have been found to have altered ion regulation, consistent with decreased
   function of the ATP1A3; BD patients have elevated intracellular Na+, Ca+ and decreased activity of the
   Na/K ATPase. Primary cultures of Myshkin mice show delayed Ca2+ clearance after stimulation with
   glutamate. Further, some BD populations have mutations in the genes for ATP1A1, ATP1A2 and
   ATP1A3. Myshkin demonstrate many symptoms of BD found in humans. Myshkin show a manic and
   depressed phenotype simultaneously, demonstrating face validity. Bipolar patients show increased
   activity in the manic state and Myshkin are hyperactive in the open field, forced swim test, tail
   suspension test, emergence test and elevated plus maze. Bipolar patients in the manic state engage in
   risk taking behaviour and Myshkin also show increased risk taking behaviour in the elevated plus maze
   and emergence test. Consistent with mania in BD, Myshkin have significantly altered circadian rhythms.
   Along with hyperactivity, increased risk taking behaviour and a longer circadian rhythm, Myshkin
   simultaneously show a depressed phenotype. They have a decreased hedonistic drive in the sucrose
   preference test and they have decreased aggression in a resident intruder paradigm. Sodium valproate
   and lithium carbonate are two common treatments for BD in humans and relive many symptoms of the
   disease. The manic symptoms in Myshkin were decreased by both sodium valproate and lithium
   carbonate indicating predictive validity of the model. There is evidence that both humans with BD and
   Myshkin have decreased function of the ATP1A3; Myshkin show the same symptoms as humans with BD
   and respond to the most effective drugs for BD. Increasing the activity of the ATP1A3 may be a useful
   target for new drug therapies for BD.




                                                     - 42 -
30. Kostelecki, Wojciech*;Velazquez, Jose Luis Perez
    Institute of Medical Science
    INFERENCE OF DIRECTED CORTICAL PROCESSING FROM MEG RECORDINGS
   The brain is a complex system that can only be understood through the simultaneous consideration of
   many interacting and evolving processes. As a result, multivariate data acquisition techniques have
   become useful tools in many aspects of brain research. Among these techniques are
   electroencephalography (EEG) and magnetoencephalography (MEG) which provide measures of the
   neuroelectric signals being produced by the brain. Although these techniques are used abundantly, the
   recordings are difficult to interpret due to the complex anatomical and functional origins of the signals
   being produced. Nevertheless, it is believed that these recordings provide important information
   pertaining to neuronal communication that supports behaviour and cognition.
   New concepts are currently being applied to the analysis of EEG and MEG recordings. One of these is
   Granger causality; a concept derived in econometrics to determine whether two or more time series
   possess a time-lagged predictive linear relationship. This study utilizes directed coherence (DC)—a
   bivariate measure that generalizes Granger causality to the frequency domain—for the inference of
   linear causality exhibited between simultaneous MEG recordings obtained while a subject performed a
   cognitive task. The task being studied required that a subject either press one of two buttons (left or
   right) with their corresponding finger in response to a specific visual instruction or to select one of the
   two responses when the visual instruction did not specify the button/finger. Successful completion of
   this task requires correct identification of the presented symbol, interpretation of its meaning and
   organization of the appropriate response. Any of these steps can be manifested as unique neuronal
   interactions and as a result, might potentially involve differences in the DC between two MEG
   recordings. Furthermore, the DC between two recordings likely varies at different points during the
   completion of a single trial. To capture the nonstationarity of such cortical interactions, the DC between
   two time series was determined for all of the experimental conditions, between every MEG sensors and
   for timescales that reflect synaptic summation (~50 ms). This analysis revealed specific differences in
   cortical processing that are exhibited for the different experimental conditions of the task. In particular,
   there were significant differences in transient interactions observed within the motor cortex and from
   the parietal cortex to the motor cortex. These findings support the use of DC in inferring causality
   between two neuroelectric recordings and can potentially be used for the identification of cognitive
   states from MEG recordings.




                                                      - 43 -
31. Labrie, Viviane1,2*; Fukumura, Ryutaro3; Rastogi, Anjali4; Fick, Laura J.5; Wei, Wang6; Boutros, Paul C.7;
    Kennedy, James L.8; Semeralul, Mawahib O.8; Lee, Frankie H.4; Baker, Glen B.9; Belsham, Denise D.5;
    Barger, Steven W.6,10; Gondo, Yoichi3; Wong, Albert H.C.8; Roder, John C.1,2
    1
     Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; 2*Institute
    of Medical Science and Program in Neuroscience, University of Toronto, Toronto, ON M5S 1A8, Canada;
    3
     Mutagenesis and Genomics Team, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba 305-0074, Japan;
    4
     Department of Pharmacology, University of Toronto, ON M5S 1A8, Canada; 5Department of Physiology,
    University of Toronto, ON M5S 1A8, Canada; 6Department of Neurobiology & Developmental Sciences,
    University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; 7Ontario Institute for Cancer
    Research, MaRS Center, Toronto, ON M5G 0A3, Canada; 8Neuroscience Division, Center for Addition and
    Mental Health, Toronto, ON M5T 1R8, Canada; 9Neurochemical Research Unit and Bebensee
    Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2G3,
    Canada; 10Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205,
    USA.
    GENETIC INACTIVATION OF SERINE RACEMASE PRODUCES BEHAVIORAL PHENOTYPES RELATED TO
    SCHIZOPHRENIA IN MICE
    Abnormal N-methyl-D-aspartate receptor (NMDAR) function has been implicated in the pathophysiology
    of schizophrenia. D-serine is an important NMDAR modulator, and to elucidate the role of the D-serine
    synthesis enzyme serine racemase (Srr) in schizophrenia, we identified and characterized mice with an
    ENU-induced mutation that results in a complete loss of Srr activity and dramatically reduced D-serine
    levels. Mutant mice displayed behaviors relevant to schizophrenia, including impairments in prepulse
    inhibition, sociability, and spatial discrimination. Behavioral deficits were exacerbated by an NMDAR
    antagonist and ameliorated by D-serine or the atypical antipsychotic clozapine. Expression profiling
    revealed that the Srr mutation influenced several genes that have been linked to schizophrenia and
    cognitive ability. Furthermore, analysis of Srr genetic variants in humans identified a robust association
    with schizophrenia. This study demonstrates that aberrant Srr function and diminished D-serine may
    contribute to schizophrenia pathogenesis, and that D-serine may be a beneficial form of treatment.




                                                      - 44 -
32. Chinta Venkateswararao, Lakshminarayan 1*; Tweed, Douglas1,2,3
    Departments of Physiology1 and Medicine2, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
    Centre for Vision Research3, York University, Toronto, Ontario M3J 1P3, Canada
    OPTIMAL SENSORIMOTOR CONTROL WITHOUT WEIGHT TRANSPORT
   Many sensorimotor control systems are at least roughly optimized, but how is optimal control learned?
   Mathematicians and engineers have found ways to do this, and have implemented them in computers.
   But a fundamental difference between computers and brains is that in the brain, not all the variables
   represented in the system are free to interact: variables that are stored as synaptic weights can’t be
   transmitted with any useful speed to other sites to interact with other variables in calculations. This is
   the problem of weight transport, and it severely constrains the set of algorithms that can run in the
   brain. Here we show how optimal control can be learned without weight transport. And we propose
   that a key element of learning in general is a set of three mechanisms that compensate for the absence
   of weight transport in the brain. To illustrate the issues we describe a specific algorithm involving
   generalized Hamilton-Jacobi-Bellman equations, but our message applies quite broadly, i.e. most control
   algorithms rely on weight transport in many different ways, but they can be recast into forms that are
   free of such transport by the mechanisms we describe.
   Supported by CIHR




                                                     - 45 -
33. Lakhani, Ekta*1,2,3; Wright, Tom2,3 Glazer, Peter3; Westall Carol1,3
    1
     Institute of Medical Science, University of Toronto; 2Ophthalmology and Vision Science, University of
    Toronto; 3Hospital for Sick Children
    CAN ELECTROPHYSIOLOGICAL MARKERS PREDICT DIABETIC RETINOPATHY?
    Background: Diabetic retinopathy (DR) is the leading cause of legal blindness among working age
    individuals. 95% of individuals with Type 1 Diabetes develop DR within 20 years of being diagnosed with
    diabetes. The current basis of diagnosis for DR involves the presence of irreversible vascular
    abnormalities in the retina. Purpose: To use electrophysiological measures to detect retinal changes
    associated with Type 1 Diabetes. Hypothesis: Recent research indicates that there may be damage to
    retinal neurons and that it may precede clinically visible vascular damage associated with DR. Methods:
    51 adolescent patients diagnosed with Type 1 Diabetes for at least 5 years and 37 healthy age-similar
    controls underwent 3 electrophysiological tests that assess retinal function: 1) standard multifocal
    electroretinogram (mfERG) which provides responses from outer and middle retinal neurons 2)
    multifocal slow-flash electroretinogram (mfOP) which provides responses from inner retinal neurons 3)
    short-wavelength electroretinogram (s-cone ERG) which provides responses from short-wavelength
    cone photoreceptors. Preliminary Results: mfERG and s-cone ERG results to date demonstrate
    significantly delayed responses in patients compared to controls. Conclusion: There is preliminary
    confirmation that abnormalities are present in the retinal neural functioning of patients with Type 1
    Diabetes prior to visible vascular damage. Future research will address whether these deficits can be
    used to predict DR pathology.




                                                      - 46 -
34. Lee, Esther1*; Steidl, Stephan2 ; Yeomans, John S. 1,2,3
    1
     Department of Cell & Systems Biology, University of Toronto, Toronto, ON; 2Department of Psychology,
    University of Toronto, Toronto, ON; 3Centre for Biological Timing and Cognition (CBTC)
    OPIATE-INDUCED LOCOMOTION DEFICITS IN M5 MUSCARINIC RECEPTOR KNOCKOUT MICE ARE
    REVERSED AFTER FOOD DEPRIVATION
   The rewarding effects of opiates are mediated through both mesolimbic DA neurons, and DA-
   independent pathways such as the pedunculopontine tegmental nucleus (PPT). Morphine induces DA
   release in the nucleus accumbens (NAc) of mice, but not in knockout (KO) mice lacking M5 muscarinic
   receptors associated with ventral tegmental nucleus (VTA) DA neurons. In contrast, M5 muscarinic
   receptor KO mice show reduced locomotion in response to systemic morphine, indicating that
   morphine-induced locomotion is mediated in part through M5 muscarinic receptors in the VTA.
   Although morphine reward is acutely mediated through PPT DA-independent pathways, morphine
   reward becomes dependent on VTA DA neurons in food-deprived rats, suggesting a switch in opiate
   reward pathways from PPT to DA neurons. Here, we examined how 18 hours food deprivation affects
   the locomotor stimulant properties of a single dose of morphine (10 mg/kg, i.p.) in wild-type (WT) and
   M5 muscarinic receptor KO mice of the C57BL/6 strain. Namely, can morphine-induced locomotor
   deficits in M5 KO mice be reversed after food deprivation? As we found previously, non-deprived WT
   mice showed greater morphine-induced locomotion relative to M5 KO mice. In food-deprived mice
   exposed to morphine, WTs showed reduced locomotion relative to non-deprived WT mice. In contrast,
   morphine-induced locomotion increased after food deprivation in M5 KO mice relative to non-deprived
   KO mice. Most importantly, in food-deprived mice, KOs showed greater morphine-induced locomotion
   compared to WTs. These results suggest that food deprivation switches the morphine effect from a M5-
   dependent DA pathway to an M5-independent DA pathway.




                                                    - 47 -
35. Lee J.-C.*; Sood M.; Sessle B.J.
    Faculty of Dentistry, University of Toronto, Canada
    OPERANT CONDITIONING OF TONGUE PROTRUSION IN MONKEYS (MACACA FASCICULARIS).
   The face primary motor cortex (MI) plays a critical role in the monkey’s performance of tongue
   movements. Bilateral cold block of face MI interferes with the ability to successfully perform a tongue-
   protrusion task. Many face MI neurons discharge in relation to the tongue-protrusion task and receive
   lingual mechanosensitive inputs. These findings raise the possibility that deprivation of lingual sensory
   input may produce impairment in the performance of the skilled tongue task. To investigate the role of
   lingual afferents in the motor control of tongue movements, a stable and measureable behavioural
   model is needed. The purpose of this study is to apply operant conditioning procedures to train the
   monkey performing the skilled tongue-protrusive movement and then to use bilateral lingual nerve
   block to test if lingual sensory input is necessary for the performance of the task. A customised
   computer program was designed to train monkey with operant conditioning procedures. The
   performance of the skilled tongue protrusion task was evaluated before and after bilateral lingual nerve
   block. Monkey reached a success rate of 75% within 33 training sessions. The learning curve fitted a
   sigmoidal model which indicated a large step increase in success from 27.8% to 75.8% around the
   inflection point. Bilateral lingual nerve block impaired the animal’s performance of the task. The effects
   were obvious at 0.5-1 hr post-injection and recovered to pre-injection level in 2-3 hr. This study has
   shown that operant conditioning and behaviour-shaping techniques can assist in training monkeys to
   perform successfully a novel skilled tongue-protrusion task. Lingual sensory input is necessary for
   successful performance of a tongue-protrusion task. Grant: CIHR MT-4918.




                                                     - 48 -
36. Lipszyc, Jonathan*; Schachar, Russell
    Institute of Medical Science
    INHIBITORY CONTROL AND PSYCHOPATHOLOGY: A META-ANALYSIS OF STUDIES USING THE STOP
    SIGNAL TASK
    Impaired response inhibition is a deficit of several psychopathological disorders, particularly attention
    deficit hyperactivity disorder (ADHD). We conducted a meta-analysis to determine whether deficient
    response inhibition as measured by the Stop Signal Task (Stop Task) is specific to patients with ADHD, or
    whether it could be found in other psychopathological disorders. A search of the literature was
    conducted using PsychInfo and Medline databases. The main Stop Task outcome variable used in the
    analysis was the stop signal reaction time (SSRT). In addition, five criteria were employed to assess the
    methodological quality of the ADHD studies only. We found a moderate effect size (ES) of 0.62 (p <
    0.001) across the ADHD studies for SSRT. Similar results were found for obsessive compulsive disorder
    (OCD) (ES = 0.79; p < 0.001) and schizophrenia (ES = 0.73, p < 0.01), but not for anxiety disorder (ES =
    0.09; ns), autism (ES = 0.40, ns), bipolar disorder (ES = 0.25; ns), conduct disorder/oppositional defiant
    disorder (ES = 0.15; ns), reading disability (ES = 0.39; p < 0.01), or Tourette syndrome (ES = 0.3, ns). For
    the ADHD studies, higher scores on the quality measure were associated, albeit not significantly, with
    inferior response inhibition. These results confirm the presence of a response inhibition deficit in
    patients with ADHD. A larger sample size is needed to establish this deficit in patients with OCD and
    schizophrenia. Our findings suggest that there may be a common mechanism underlying impaired
    response inhibition in ADHD, OCD, and schizophrenia. Further neuropsychological and neuroimaging
    studies are needed to clarify this deficit in response inhibition.




                                                       - 49 -
37. Liu, Zhongxu*; Lewis, Marc D.
    Department of Human Development and Applied Psychology, University of Toronto
    CHILDREN’S BRAIN SIGNAL VARIABILITY AND BEHAVIORAL PERFORMANCE
   McIntosh, Kovacevic, & Itier (2008) found that brain EEG cross-trial variability (e.g., measured by the
   number of principal components [PCs] in the trial space that accounted for 90% cross-trial variability)
   was negatively associated with behavioral variability in children. However, in this previous study, the
   time range of the post-stimulus EEG signals used to calculate the brain signal variability seemed
   arbitrarily determined and fixed at 200ms. Whether choosing different time ranges will have different
   results is unclear. Moreover, for the same post-stimulus time range, brain signals for participants with
   faster reaction time may contain more ERP components. This ERP component variability may contribute
   to the cross-trial brain signal variability. Therefore, it is unclear whether the relationship between brain
   signal cross-trial variability and behavioral performance remains after controlling for participants’ ERP
   component variability. The current study attempted to clarify these questions and explore how this
   brain-behavior relationship changed under different task conditions.
   Fifty children (8-16 years old) completed an emotional go/no-go task. Data from the first two blocks
   were used in this analysis: Block A is a regular go/no-go task, but in block B, negative emotions were
   induced by providing negative feedback. Then, principal component analysis was conducted on go-trial
   EEG signals with three different post-stimulus time ranges (240ms, 380ms, and 600ms) and the average
   PC numbers were obtained to index individuals’ brain signal cross-trial variability. Individuals’ ERP PC
   numbers in the channel space were also calculated.
   A negative relationship between the brain signal variability, i.e., trial-space PC number, and behavioral
   performance, i.e., mean reaction time (RT) and its standard deviation (rtSD), was found, which was
   similar to the previous findings. But it was also found that this brain-behavior relationship was strongest
   for the 240ms time range (r = -.31, p <05 for RT and r = -.32, p < .05 for rtSD) and disappeared for the
   600ms time range (r = -.16 & r = -.22, p = ns, respectively), which may indicate that the importance of
   the brain signal variability varies in different time windows. The results also showed that, after
   controlling for the channel-space ERP PC number variability, the negative relationship between the brain
   signal variability and behavioral performance disappeared for block A, but remained unchanged for
   block B. These results may indicate that the cross-trial brain signal variability, which may reflect the
   complexity of the brain activities, becomes more important for achieving a faster and more stable
   behavioral performance only when the tasks become more difficult.
   Reference
   McIntosh, A. R., Kovacevic, N., & Itier, R. (2008). Increased brain signal variability accompanies lower
   behavioral variability in development. PLoS Computational Biology, 4, e1000106.
   doi:10.1371/journal.pcbi.1000106.




                                                      - 50 -
38. Lu, T.Z.*; Feng, Z.P.
     Department of Physiology, Faculty of Medicine, University of Toronto, 1 King’s College Circle, Toronto,
    Ontario, Canada, M5S 1A8.
    FUNCTIONAL STUDY OF A NON-SELECTIVE CATION CHANNEL IN AERIAL RESPIRATORY MODEL -
    LYMNAEA STAGNALIS.
    Respiratory rhythm is largely dependent on the synaptic and spontaneous activity of the central pattern
    generator (CPG) neurons. The resting membrane potential is one of the key factors to regulate neuronal
    activity. NALCN (sodium leak current, nonselective) is a newly described cation channel characterized as
    voltage-independent, nonselective, and noninactivating. It is responsible for a Na+ leak current at rest;
    thus potentially contribute toward neuronal excitability. Targeted deletion the NALCN gene in mice
    resulted in abnormal respiratory rhythmic activity and postnatal pups do not survive beyond 24 hours,
    which may be caused by inadequate development of the respiratory neuronal network. However,
    whether and how the NALCN channel affects mature respiratory neuronal activity has not been tested.
    Fresh water pond snail, Lymnaea stagnalis, displays the aerial respiratory behaviour and has served as a
    practical model to study the cellular mechanisms underlying regulation of respiratory CPG activities.
    Recently a NALCN orthologue, termed U-type voltage gated calcium channel, have been cloned in L.
    stagnalis central ganglia. Protein alignment shows 55% identity of the U-type channel with the
    mammalian NALCN isoform. More importantly, alignment data indicate high homology in the pore and
    S4 region of the protein. It is interesting to understand the functional role of the U-type channel in
    respiratory neurons. In this study, we are using RNA gene silencing approach to knockdown U-type
    channels and testing whether U-type channel is responsible for a resting leak current that regulates
    respiratory CPG neuron excitability in L. stagnalis. We first introduced the specific U-type channel dsRNA
    in to the snail and confirmed U-type channel gene expression was partially reduced following the
    specific dsRNA injection through semi-quantitative RT-PCR analysis. We found that a significant
    reduction of respiratory activity in L. stangalis correlated to the partial U-type channel knockdown.
    Whole-cell patch clamp recording was then carried out to study the U-type channel current properties in
    the identified respiratory CPG neurons. We found that a partial knockdown U-type channel gene
    resulted in a reduction of an inward rectifier hyperpolarizing cation current component, which is likely
    being responsible by U-type channel. Our observations indicate expression of a functional U-type
    channel in the respiratory network on L. stagnalis. Future experiments will be carried out to investigate
    the biophysical properties of the hyperpolarizing cation current and study the contribution of the
    current in membrane excitability and synaptic activity of respiratory CPG neurons. This study will
    provide new insight into the regulatory mechanisms of respiratory rhythm activity.




                                                      - 51 -
39. Marsolais, A.J.1,2; Sheth, R.1,3; Yiu, A.P.1,4; Egan, S.E.1,5; Josselyn, S. A.1,2,4
    1
     The Hosp Sick Children, Toronto, ON, Canada; 2Physiol.,3Hum. Biol., 4Inst. of Med. Sci.,5Mol. Gen., Univ.
    of Toronto, Toronto, ON, Canada
    THE ROLE OF NOTCH SIGNALING IN LEARNING AND MEMORY
    The Notch signaling pathway is a ubiquitous and highly conserved pathway typically involved in cell fate
    decisions and embryonic development in organisms as diverse as Drosophila melanogaster,
    Caenorhabditis elegans and humans. It is now understood that, in addition to its role in development,
    Notch signaling plays important roles in adult processes, including long-term memory (LTM) formation
    (Costa et al., 2005). In mice, heterozygous mutations in the Notch1 gene result in deficits in spatial LTM
    (Costa et al., 2003). Notch signaling has also been shown to be important for synaptic long-term
    potentiation in the CA1 region of the hippocampus, a cellular process strongly associated with memory
    formation (Wang et al., 2004). Additionally, interest has arisen around the role of Notch signaling in
    memory loss associated with Alzheimer’s disease (AD) since Notch signaling depends on γ-secretase
    (mutations of which are the main genetic determinant of familial AD) (Steiner et al., 2008). We
    examined memory in mice deficient in critical components of the Notch pathway (Jagged1+/- and Delta-
    like 1+/- mice). Our results suggest that Jagged1+/- mice not Delta-like 1+/- mice display deficits in the
    Morris water maze (MWM), a measure of spatial LTM. Since mice reach adulthood without gross
    anatomical or developmental abnormalities, we believe the deficits observed in the MWM are due to
    impaired Notch signaling at the time of testing, confirming a role for the Notch pathway in adult
    memory processes. We are now characterizing the behavioral deficits observed at the cellular level
    using the Golgi-Cox staining technique and tracing of neurons using computer software, where we hope
    to observe 1) differences in dendritic branching and 2) differences in spine densities in the CA1 region of
    the hippocampus.
    Costa, RM, Honjo, T, Silva, AJ. Learning and memory deficits in Notch mutant mice, Curr. Biol. (2003)
    13:1348-1354.
    Costa, RM, Drew, C, Silva, AJ. Notch to remember. Trends Neurosci (2005) 28:429-35.
    Steiner H, Fluhrer R, Haass C. Intramembrane Proteolysis by {gamma}-Secretase. J Biol Chem (2008)
    283:29627-31.
    Wang, Y, Chan, SL, Miele, L, Yao, PJ, Mackes, J, Ingram, DK, Mattson, MP, Furukawa, K. Involvement of
    Notch signaling in hippocampal synaptic plasticity. Proc Natl Acad Sci U S A (2004) 101:9458-62.




                                                       - 52 -
40. Martinez-Canabal, Alonso*1, 2; Lerch, Jason5; Buckwalter, Marion4; Spring, Shoshana5; Sled, John5,6;
    Wyss-Coray, Tony4; Frankland, Paul William1,2,3.
     1
      Department of Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1X8
    Canada; 2Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8 Canada;
    3
     Department of Physiology, University of Toronto, ON M5S 1A8 Canada; 4Department of Neurology and
    Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA; 5Mouse
    Imaging Centre, Hospital for Sick Children, Toronto, ON M5T 3H7 Canada; 6Department of Medical
    Biophysics, University of Toronto, Toronto, ON M5G 2M9 Canada.
    CHRONIC OVER-EXPRESSION OF TRANSFORMING GROWTH-FACTOR BETA1 (TGF-B1) NEGATIVELY
    IMPACTS BRAIN FUNCTION AND COGNITION
   The TGF-beta1 is an inhibitory cytokine commonly described as an anti-proliferator, anti-inflamatory and
   anti-apoptotic factor that is found to be up-regulated during Alzheimer disease and brain injury. To
   examine the long term consequences of chronically increased TGF-beta1 secretion, we used transgenic
   mice with an insertion of the active form of porcine TGF-beta1 gene driven by a GFAP promoter. Using
   this model we show that chronic overexpression of TGF-beta1 impairs cognition, brain structure and
   neurogenesis. 12-month old TGF-beta1 overexpressing mice were impaired in spatial learning in the
   water maze and were hyperactive in the open field paradigm, however they have not shown this
   behavioural differences in 2-month old. In contrast, contextual fear, object recognition and tail
   suspension test show no difference. Consistent with spatial learning deficits, there is a neurogenesis
   decrease in the hippocampal subgranular zone (but not subventricular zone) of the TGF-beta1 mice.
   Furthermore, magnetic resonance imaging revealed structural changes, especially evident in
   hippocampus and enthorhinal cortex. These data suggest that chronic overexpression of TGF-beta1 has
   a negative impact on cognition and brain function in an age related frame.




                                                     - 53 -
41. Nejatbakhsh, N1*; Guo CH1; van Kesteren RD2; Feng ZP1
    1
     Dept. of Physiology, University of Toronto, Toronto, Ontario, Canada; 2Dept. of Molecular & Cellular
    Neurobiology, Vrije Universiteit, Amsterdam, The Netherlands
    REGENERATION OF CENTRAL NEURONS IN LYMNAEA REQUIRES LOCAL SYNTHESIS OF A NOVEL CALCIUM
    BINDING PROTEIN
   Local transcripts are thought to play a crucial role in neuro-regeneration following neuronal injury. The
   transcripts of a novel calcium binding protein, LCaBP, are found not only in the somata, but also in the
   neurites and growth cones of Lymnaea central neurons. The objective of this study was to determine the
   role of LCaBP transcripts in neurites and growth cones in neuro-regeneration of injured Lymnaea
   neurons. We used a siRNA knockdown approach to effectively reduce levels of LCaBP mRNA and protein
   in cultured PeA cells of Lymnaea. The incidents of outgrowth and rates of elongation were measured
   compared over a period of 30 hours in LCaBP siRNA and scrambled siRNA treated cells. To identify the
   potential role of locally synthesized LCaBP, we measured and compared the lengths of intact neurites
   and neurites severed from their soma in cells treated with LCaBP specific or control siRNA, as well as
   comparison of neurites under pharmacological condition where axono-somatic transport was blocked.
   We found that adequate LCaBP levels are crucial for neurites to initiate outgrowths and elongate.
   Isolated neurites severed from their cell body were only able to maintain their length and elongate
   under the control condition, whereas isolated neurites treated with LCaBP siRNA experienced a net
   retraction over 30 hours. Application of a somato-dendritic blocker caused a retraction in siRNA treated
   cells, but had no significant effect on the length of neurites of control treated cells. Fura-2 calcium
   imaging showed that LCaBP reduces the activity dependent calcium influx in growth cones following
   graded stimulation, and that it increases the rate of time dependent calcium decay kinetics at both high
   and low levels of somatic stimulation. Immunocytochemistry staining demonstrated the differential
   effects of LCaBP on tubulin and actin protein expressions. Our data indicates that LCaBP is an essential
   protein for neurite outgrowth initiation, elongation and regeneration in central neurons of Lymnaea,
   likely acting through modulation of activity dependent calcium signals and expression levels of certain
   cytoskeleton proteins.




                                                    - 54 -
42. Pacey, Laura K.K.1; Heximer, Scott P.2; Hampson, David R.1,3
    1
     Leslie Dan Faculty of Pharmacy ; Departments of 2Physiology and 3Pharmacology, University of Toronto
    RESCUE OF AUDIOGENIC SEIZURES IN FRAGILE X AND RGS4 DOUBLE KNOCKOUT MICE
   Mice lacking the gene encoding fragile X mental retardation protein (FMR1) are susceptible to
   audiogenic seizures and antagonists of the Group I metabotropic glutamate receptors (mGluRs) have
   been shown to block seizures in FMR1 knockout mice. We investigated whether the G-protein inhibitory
   activity of the regulator of G-protein signaling protein, RGS4, could also alter the susceptibility to
   audiogenic seizures in FMR1 mice. Surprisingly, male FMR1/RGS4 double knockout mice showed
   reduced susceptibility to audiogenic seizures compared to age-matched FMR1 mice. These data raised
   the intriguing possibility that loss of RGS4 increased signaling through another G-protein pathway that
   reduces seizure susceptibility in FMR1 mice. Indeed, administration of the GABAB receptor agonist
   baclofen to FMR1 mice inhibited seizures, while the GABAB receptor antagonist CGP 46381 increased
   seizure incidence in double knockout mice but not in wild-type mice. Lastly, audiogenic seizures could
   be induced in wild-type mice by co-administering CGP 46381 and the mGluR5 positive allosteric
   modulator CDPPB. These data show for the first time that GABAB receptor-mediated signaling
   antagonizes the seizure-promoting effects of the mGluRs in FMR1 knockout mice and point to the
   potential therapeutic benefit of GABAB agonists for the treatment of fragile X syndrome.
   POST-DOCTORAL FELLOW PRESENTATION – NOT INCLUDED IN COMPETITION




                                                    - 55 -
43. Pisterzi Luca F.1*; Stoneman, Michael R.2, Wells James W. 1; Raicu, Valerică2
    1
     Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON; 2Departments of Physics and
    Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI.
    OLIGOMERIC SIZE OF THE M2 MUSCARINIC RECEPTOR IN LIVE CELLS AS DETERMINED FROM FRET
    EFFICIENCIES AT THE LEVEL OF SINGLE PIXELS
   G protein-coupled receptors are known to form oligomers, but their size (n) is unclear. We therefore
   have developed an approach whereby an explicit value of n can be obtained from the efficiency of
   fluorescence resonance energy transfer (FRET) measured between fluorophore-tagged receptors at the
   level of single pixels. That approach has been applied to M2 receptors fused at the N-terminus to
   enhanced green or yellow fluorescent protein (EGFP2-M2 or EYFP-M2) and coexpressed in Chinese
   hamster ovary cells. Pixel-level emission spectra were recorded from images captured in a single plane,
   and the pair-wise FRET efficiency (E) was calculated from the relative contributions of EGFP2-M2 and
   EYFP-M2 as determined by spectral deconvolution. The number of efficiencies obtained for an oligomer
   of given size is expected to depend upon the number of combinatorial arrangements of FRET-productive
   pairs as predicted by the binomial theorem. A dimer will reveal a single efficiency, for example, and a
   square tetramer will reveal at least three. A sum of three Gaussians was required to describe the
   distribution of efficiencies obtained from cells coexpressing EGFP2-M2 and EYFP-M2. Also, differences
   among values of E in an oligomer of specified size can be predicted on the basis of a model in which the
   apparent FRET efficiency is determined by the pair-wise FRET efficiencies for all combinations of donors
   and acceptors. With the present data, the observed differences in the mean values of E agree with the
   predicted differences when n is 4. The M2 receptor therefore can be identified as a tetramer, in
   agreement with the results of a parallel study in which the oligomeric size has been estimated from
   intensity-based FRET and fluorescence lifetimes.




                                                    - 56 -
44. Proulx, Éliane1*;Young, Edwin J.2; Osborne, Lucy R.2; Lambe, Evelyn K.1,3
    1
     Departments of Physiology; 2Molecular Medical Genetics; 3Obstetrics and Gynecology, Faculty of
    Medicine, University of Toronto
    ALTERED PREFRONTAL MODULATION IN A TRANSGENIC MOUSE WITH A LOW ANXIETY PHENOTYPE
   Williams syndrome is a neurodevelopmental disorder caused by a genetic deletion of approximately 25
   genes including the general transcription factor GTF2IRD1. A Gtf2ird1 knockout (KO) mouse has been
   generated and found to exhibit the decreased anxiety, enhanced sociability and reduced aggression
   characteristic of Williams patients. Yet, it is not known how deleting this transcription factor affects the
   neuromodulation of brain areas important in coping with anxiety. We hypothesized that the anxiolytic
   phenotype of these mice would be associated with greater than normal modulation of prefrontal
   neurons by serotonin 5-HT1A receptors, which are known for their anxiolytic effects in prefrontal cortex.
   By contrast, we hypothesized that these mice would have lower than normal prefrontal modulation by
   group I metabotropic glutamate receptors, which are thought to be anxiogenic. To assess the functional
   effects of these receptors, we performed whole cell recordings in layer V pyramidal cells in PFC of adult
   Gtf2ird1 knockout mice and their wildtype siblings and measured peak currents in response to bath
   application of 5-HT or the mGluR1/5 agonist DHPG. Serotonin elicited significantly larger outward
   currents in KO than in WT. In prefrontal slices from both KO and WT mice, these currents were
   completely blocked by the selective 5-HT1A antagonist WAY-100635. We next investigated the inward
   currents elicited by group I mGluR receptors in layer V pyramidal neurons by application of the selective
   agonist DHPG in prefrontal slices from KO and wildtype mice. As hypothesized, these currents were
   significantly smaller in the KO than the WT mice. We conclude that 5-HT1A mediated responses are
   enhanced and group I mGluR mediated responses are impaired in Gtf2ird1 mutant mice. These findings
   fit well with the low anxiety phenotype observed in these animals and help elucidate the mechanisms of
   Williams Syndrome while providing insight into potential therapeutical targets.
   This study was funded by the Scottish Rite Charitable Foundation (EKL) and a CIHR Frederick Banting and
   Charles Best CGS Doctoral Award (EP).




                                                      - 57 -
45. Ratnam, Melanie *; Aarts, Michelle
    University of Toronto, Cell and Systems Biology; Centre for the Neurobiology of Stress
    TRPM2 & TRPM7: CELL-SPECIFIC EXPRESSION IN THE BRAIN
    The Transient Receptor Potential Melastatin (TRPM) calcium channels, TRPM2 and TRPM7, have been
    implicated in mediating cell death in anoxia and oxidative stress. However, cell-specific expression in the
    brain is a subject of some debate. Since the expression of these receptors may play a role in regulating
    physiologic functions, it is important to delineate receptor expression under these normal conditions.
    Our goal was to determine cell-specific expression of TRPM2 and TRPM7 during brain development (in
    vivo and in vitro). In situ hybridization was used to co-localize gene expression with specific cell markers
    (i.e. NeuN, GFAP). First, we examined gene expression in age-specific brain tissue sections. Second, we
    examined gene expression in primary cortical neuronal culture.




                                                       - 58 -
46. Rosenzweig, S*; Czerwinska E; Orser B.A.; Wojtowicz J. M.
    Departments of Physiology, Faculty of Medicine, University of Toronto.
    ABNORMAL DEVELOPMENT OF ADULT BORN NEURONS IN THE DENTATE GYRUS OF GABAAR-DELTA
    KNOCKOUT MICE
   During adult neurogenesis, new cells are born in the Sub-granular zone (SGZ) of the dentate gyrus (DG)
   and undergo differentiation, migration and maturation. While many factors are known to affect these
   developmental stages, the exact mechanisms of regulation remain largely unknown. One such regulator
   is the neurotransmitter GABA, which depolarizes young DG cells before they become responsive to
   glutamate. This early depolarization initially occurs extrasynaptically via GABAA receptors. As most
   extrasynaptic GABAA receptors in the DG contain the delta subunit, we hypothesized that this type of
   receptor is involved in the early depolarization and developmental regulation of young DG neurons. To
   test this hypothesis we characterized and compared neurogenesis in the DG of delta-subunit Knockout
   (Δ-/-) and wild type (WT) C57BL/6J mice. Two months old WT and Δ-/- mice were intra-peritoneally
   injected with the mitotic indicator BrdU and sacrificed two weeks later. Hippocampal sections were
   stained using immunohistochemistry for Ki-67, a marker for proliferating cells, doublecortin (DCX), a
   marker for immature neurons, and BrdU. Labeled cells were counted using a confocal microscope. We
   found no genotype-related differences in the number of Ki-67+ and two-weeks old (BrdU+) cells. The
   total number of immature (DCX+) neurons, as well as the percentage of immature BrdU+ cells, were
   over 20% higher in Δ-/- compared to WT mice (p<0.03 and p<0.01, n=3). Analysis of the position of
   BrdU+ cells across the granule cell layer (GCL) revealed that in WT mice, 22% of the cells have migrated
   from the SGZ deeper into the GCL by two weeks. This was in contrast to Δ-/- mice where only 9.8% of
   the cells have migrated (p<0.01, n=3). These results indicate that while proliferation and two-week
   survival is unchanged in Δ-/- mice, a larger proportion of young cells remain immature, and their normal
   migration is disrupted compared to WT mice.




                                                    - 59 -
47. Rowland, James W. *; Lee, Jason J.; Schut, Desiree; Eftekharpour, Eftekhar; Fehlings, Michael G.
    Institute of Medical Science, Toronto Western Research Institute, University Health Network, Division of
    Neurosurgery, University of Toronto.
    ASSESSING THE ABILITY OF PRIMITIVE NEURAL STEM CELLS DERIVED FROM MOUSE EMBRYONIC STEM
    CELLS THROUGH A DEFAULT MECHANISM TO PROMOTE REMYELINATION OF DYSMYELINATED CNS
    AXONS.
    INTRODUCTION: The remyelination of spared, demyelinated axons has emerged as a promising
    therapeutic strategy to improve neurological function following CNS trauma. Cell-based remyelinating
    therapies have shown promise in animal studies and have begun clinical translation. However, the
    optimal source and protocols for obtaining neural, or specifically oligodendrocyte, precursor cells for
    transplantation remain to be determined. Here, we investigated the use of the default mechanism of
    neural differentiation in mouse embryonic stem cells (R1 line) to produce primitive neural stem cells
    (pNSCs) for transplantation to repair dysmyelinated axons.
     HYPOTHESIS: pNSCs generated through the default mechanism of neural differentiation can
    remyelinate axons in vivo and represent a feasible substitute for adult derived neural stem cells.
    METHODS: R1 mES cells were initially grown under standard conditions on feeder cells. ES colonies were
    then dissociated and transferred into minimal serum free conditions at clonal density (10 cells/µl) to
    produce floating neurosphere colonies that could be passaged repeatedly in the presence of LIF and
    FGF2. To examine the in vitro differentiation pattern, neurospheres were transferred to serum free
    media containing 1% FBS on matrigel coated culture dishes to which they adhered and began to
    differentiate. Following 7 days of differentiation immunocytochemistry was performed to evaluate the
    cell types produced. To assess the ability of pNSCs to survive, differentiate into oligodendrocytes and
    form myelin in vivo cells were transplanted into the spinal cords of dysmyelinated Shiverer mice that
    lack compact central myelin due to a deletion in the myelin basic protein gene. At 6 weeks post
    transplantation we assessed the differentiation pattern and the myelinating capability of pNSCs and
    compared it to that of adult neural precursor cells (aNPCs) using immunohistochemistry and confocal
    microscopy.
    RESULTS: Upon in vitro differentiation pNSCs produce all three cell-types of the neural lineage. pNSCs
    produce a more heterogenous cell population compared to aNPCs, some of which fail to express the
    neural markers investigated. Following intraspinal transplantation 35% of pNSCs express
    oligodendrocyte lineage markers (Olig2, CNPase, PDGFRα) compared to 48% for aNPCs. For both cell
    types, the oligodendrocytes generated associated with host axons and expressed MBP indicating
    remyelination. Functional significance of the observed remyelination was suggested by evidence for the
    re-organization of axonal potassium channels to the appropriate juxtaparanodal regions in areas of
    transplant-mediated remyelination. The pNSCs not expressing neural antigens produced some non-
    neural cells indicating incomplete neural lineage commitment within the pNSC population.
    CONCLUSIONS: The default mechanism of neural induction shows promise as a potential method of
    deriving neural or oligodendrocyte lineage cells from pluripotent cell populations for remyelinating
    therapies. The default mechanism of neural induction shows promise as a potential method of deriving
    neural or oligodendrocyte lineage cells from pluripotent cell populations for remyelinating therapies.



                                                     - 60 -
48. Sam, Kevin*; Aarts, Michelle M.
    Cell and Systems Biology, University of Toronto
    CHARATERIZATION OF BINDING PARTNERS OF THE NMDAR NR2 SUBUNITS
   A daunting picture of the molecular complexity of the postsynaptic specialization (PSD) of glutamatergic
   synapses has emerged over the last decade. Glutamatergic synapses involve the accumulation of N-
   methyl-D-aspartic acid receptors (NMDARs) at postsynaptic sites. These cation channel receptors are
   responsible for excitatory communication in the brain and have implications in learning, memory,
   synaptic plasticity, as well as both neurotrophic and neurotoxic signalling following acute brain injury.
   The NMDAR is a tetrameric complex composed of an NR1 subunit with one or more NR2 subunits. The
   NR2 subunit are differentially expressed and are thought to play varying roles in the central nervous
   system. My research will focus particularly on the NR2A and NR2B subunits, which are expressed in the
   mature cortex and hippocampus and provide the most significant contribution to plasticity and
   neurotoxicity. The differential roles of NR2A and NR2B containing-NMDAR during excitatory
   neurotransmission may be determined by the vast array of scaffolding molecules, such as the
   postsynaptic density protein PSD-95, which binds directly to the intracellular tails of the NMDAR
   subunits and serves as a linker to cytoskeletal elements, signal adaptors, and enzymes. Uncoupling PSD-
   95 from the NMDAR has been shown to be neuroprotective; however, a clear understanding of the
   balance between specific neuroprotective and neurotoxic signal transduction mechanisms associated
   with individual NR2 subunits and their roles in receptor physiology or pathophysiology remains to be
   elucidated. My research will focus on the differential roles of NMDAR subunits in mediating
   neuroprotection by uncoupling their interaction with scaffolding molecules of the PSD-95 family. To
   examine the role of each NMDAR NR2subunit in cellular signalling by identifying binding partners of the
   cytosolic tails of NR2 subunits, GST- fusion proteins containing the entire NR2A or NR2B c-terminus were
   generated to pull down interacting proteins in the presence or absence of synthetic peptides which
   block NMDAR interaction with PSD95 family proteins. In this way, protein interactions critical for
   mediating the differential influences of individual NMDAR NR2 subunits on neuronal survival or death
   will be discerned.




                                                     - 61 -
49. Siddiq, Ishita*;Park, Eugene; Liu, Elaine;Baker, Andrew
    Cara Phelan Center for Trauma Research, St. Michael's Hospital, Toronto; Institute of Medical Science,
    Faculty of Medicine, University of Toronto
    UPREGULATION OF VEGF-A USING ENGINEERED ZINC FINGER PROTEIN GENE THERAPY REDUCES
    APOPTOTIC CELL DEATH AFTER LATERAL FLUID PERCUSSION INJURY IN RATS
    Introduction: Vascular endothelial growth factor (VEGF) has been characterized to have neuroprotective
    properties after traumatic brain injury (TBI) in addition to being a regulator of neovascularisation
    signalling mechanisms (1). An exogenous increase of the VEGF-A isoform has been shown to correlate
    with a reduction in the infarct size, enhanced survival of newborn neurons and improved neurological
    performance (2). Conversely, inhibition of the VEGFR2 receptor in endothelial cells has shown to
    increase the haemorrhagic area and increase neuron-specific enolase and S100? serum levels suggesting
    increased neuronal and glial death (3). A novel gene therapy approach, using an adenovirus carrying an
    engineered zinc-finger protein (Adv-ZFP) activating VEGF transcription factor, has been shown to
    successfully upregulate genomic expression of VEGF, and all its isoforms in their proper biological ratios,
    in rat skeletal muscle and promote wound healing (4).
    Hypothesis: Based on data supporting a neuroprotective role of VEGF, the presented study focuses on
    the use of Adv-ZFP-VEGF gene therapy as an effective interventional strategy to limit delayed cell death
    after TBI.
    Methods: Male rats subjected to a unilateral fluid percussion injury in the cortex were treated at 10
    minutes post-trauma with the Adv-ZFP-VEGF (5x1010 pfu/ml, 2?l x 4 injections). Groups consisted of
    control (craniotomy, injury and vehicle injection) and treatment animals (craniotomy, injury and Adv-
    ZFP-VEGF injection). Western blotting and immunohistochemistry was used to validate cell infection by
    the virus and VEGF upregulation. Apoptotic cell death was assessed at 3 days and 7 days post-injury in
    the hippocampus and cortex using TUNEL.
    Results: Results demonstrate successful infection of cells and increased VEGF protein levels in Adv-ZFP-
    VEGF groups. Quantitative double label immunohistochemistry for TUNEL and caspase 3 activation
    show a reduction in apoptotic cell death in Adv-ZFP-VEGF groups at 3 and 7 days compared to controls.
    Conclusion: Delayed cell death following TBI continues to be a major cause of morbidity and mortality.
    One therapeutic approach to this problem is to aid endogenous reparative mechanisms. The presented
    novel form of gene therapy using engineered zinc finger proteins to upregulate VEGF has shown to be
    successful in increasing its protein levels and consequently reducing apoptotic cell death.
    Acknowledgements:
    Sangamo BioScience and Li Ka-Shing Knowledge Institute at St. Michael’s Hospital.
    (1)Skold, M.K., et al., VEGF and VEGF receptor expression after experimental brain contusion in rat. J
    Neurotrauma, 2005. 22(3): p.353-67.
    (2)Sun, Y., et al., VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral
    ischemia. J Clin Invest, 2003.111(12): p. 1843-51.
    (3) Skold, M.K., et al., Inhibition of vascular endothelial growth factor receptor 2 activityin experimental
    brain contusions aggravatesinjury outcome and leads to early increased neuronal and glial
    degeneration. Eur J Neurosci, 2006. 23(1): p. 21-34.
    (4) Liu, P.Q., et al., Regulation of an endogenous locus using a panel of designed zinc finger proteins

                                                        - 62 -
targeted to accessible chromatin regions. Activation of vascular endothelial growth factor A. J Biol Chem,
2001. 276(14): p. 11323-34.




                                                  - 63 -
50. Sinopoli, Katia J.*; Max, J.; Levin, H.; Li, X.; Schachar, R.; Dennis, M.
    *Department of Psychology and the Collaborative Program in Neuroscience, University of Toronto, and
    the Program in Neurosciences and Mental Health, the Hospital for Sick Children
    RELATIONS AMONG MECHANISM OF INJURY, INJURY SEVERITY, AGE AT INJURY, AND PRE-MORBID
    BEHAVIOURS IN CHILDHOOD TRAUMATIC BRAIN INJURY
   Survivors of childhood traumatic brain injury (TBI) often endure life-long cognitive-behavioural
   problems. While younger age at injury often predicts more severe injuries and more negative cognitive-
   behavioral sequelae, there is little research concerning how pre-morbid behaviours contribute to the
   mechanism of injury, and how each of these variables contributes to the severity of TBI. We first
   classified 120 children with mild to severe TBIs on mechanism of injury and whether or not the child’s
   behaviour contributed to the TBI. The most common cause of injuries was falls (χ2=37.6, df =2,
   p<0.0001), with the behaviour of the children themselves contributing significantly to the falls (χ2=38.9,
   df=5, p<0.0001). TBI under age 7 was significantly related to falls, whereas TBI over age 7 was
   significantly related to pedestrian accidents (χ2=15.5, df =2, p<0.0001). Children whose behaviour
   contributed to their own injuries were more likely to be over age 7 (χ2=12.3, df =2, p=0.002). Falls were
   responsible for more mild and complicated mild injuries, falls and pedestrian accidents were more
   common in moderate TBIs, and severe TBIs were caused equally by falls, motor vehicle, and pedestrian
   accidents (χ2=16.2, df =6, p=0.012). We next examined whether pre-morbid behavioural characteristics
   were related to the severity and the mechanism of injury in 33 children for whom pre-injury data were
   available. Contrary to hypotheses, pre-morbid attention and/or externalizing behaviour problems was
   not significantly related to the mechanism of injury or to TBI severity. Mechanism of injury is related to
   age at injury and injury severity but not pre-morbid behaviours.




                                                     - 64 -
51. Srejić, Luka R *1,3,5; Aarts, Michelle6; Hutchison, William D2,3,4
    1
     Div’s of Fundamental Neurobiology & 2Brain Imaging and Behaviour, Toronto Western Research
    Institute; Dept’s of 3Surgery, 4Physiology and 5Cell and Systems Biology, Univ. of Toronto; 6Life Sciences,
    Biology, Univ. of Toronto at Scarborough
    APPLICATION OF TAT-NR2B9C LEADS TO ENHANCED RECOVERY OF SPONTANEOUS AND EVOKED
    POTENTIALS FOLLOWING CORTICAL STROKE IN THE RAT
    Spontaneous and thalamocortical evoked potentials (EPs) were recorded with anteroposterior 8-channel
    microelectrode array before, during, and up to 3h following cauterization of the distal branches of the
    middle cerebral artery (MCA) in urethane-anaesthetized rats. Control experiments were performed in 6
    rats with the same time course but without arterial coagulation. In addition to stroke-only experiments,
    anti-stroke peptide Tat-NR2B9c (3nmol/g) was administered via tail vein injection to 5 rats 5min before
    ischemia. Fast Fourier transforms (FFT) of spontaneous potentials were taken and the area under curve
    (AUC) of the low frequency oscillations (2-8 Hz) at 20min and 1h post stroke were analyzed after
    normalization with baseline. Two-way ANOVA (with post hoc comparisons) was used to determine
    significance of EEG power loss and attenuation of EPs.
    At 20min and 1h after stroke, spontaneous EEG activity in the stroke-only group (n=8) decreased in
    power to 35% and 50% of baseline, respectively. This was a significant reduction compared to the
    control group (p<0.001), which had a stable baseline of power over the same time period. A greater loss
    of EEG power was observed on anterior electrodes closer to the occluded area when compared to
    posterior contacts (p<0.05). The Tat-NR2B9c+stroke group lost significantly less power at both 20min
    (52% of baseline) and 1h (70% of baseline) when compared to stroke-only rats (p<0.05). All components
    attenuated to baseline within 3min of ischemia. EP amplitude in the stroke-only group was significantly
    reduced following ischemia (62% of baseline) when compared to controls (p<0.001). There was only
    slight EP suppression of the Tat-NR2B9c+stroke group (92% of baseline), which was significantly greater
    than the stroke-only group (p<0.001), but not different from the controls (p=0.642).
    Systemic application of Tat-NR2B9c slows the progression of stroke-related neurophysiological
    dysfunction as evidenced by less EEG flattening and increased recovery of thalamocortical evoked
    potentials.




                                                       - 65 -
52. Taylor, K.S. *; Anastakis, D.J.; Davis, K.D.
    Department of Surgery and Institute of Medical Science, University of Toronto, Toronto Western
    Research Institute, UHN
    FUNCTIONAL AND STRUCTURAL CORTICAL PLASTICITY FOLLOWING PERIPHERAL NERVE TRANSECTION
   Introduction: Plasticity can occur throughout the neuroaxis following peripheral nerve injury (PNI) but
   the mechanism underlying PNI induced cortical plasticity in humans is not well understood. Thus, the
   aim of this study was to determine whether indices of somatosensory function in patients with
   peripheral nerve transection followed by surgical repair (PNIr) are associated with corresponding
   changes in fMRI sensory responses and/or structural (gray and white matter) cortical changes. Methods:
   Sensorimotor tests and MRI scans were obtained from pain-free patients who had sustained a complete
   transection of the right median and/or ulnar nerve followed by surgical repair at least 1.5 years prior to
   the study, and age- and sex-matched healthy controls (HC). All participants underwent sensorimotor
   testing and an MRI session that included: 1) fMRI consisting of vibratory stimulation (12Hz) delivered to
   the right index finger; 2) a high resolution T1-weighted anatomical scan acquired for cortical thickness
   analysis (CTA); 3) two diffusion tensor imaging (DTI) scans. Results: Patients had increased mechanical
   and vibration detection thresholds. The CTA analysis showed cortical thinning of the contralateral
   primary (S1) and secondary (S2) somatosensory cortex, and right anterior insula (aIC) in the PNIr
   patients compared to HC. Interestingly, cortical thinning in patients correlated with their mechanical and
   vibration threshold deficits in the contralateral S1 and S2. Patients also showed reduced fractional
   anisotropy in the right insula. Finally patients with right median PNIr displayed significantly less
   activation in the contralateral S1 and S2 during stimulation of the right median nerve territory.
   Conclusion: These results indicate that PNIr is associated with structural and functional cortical changes
   that may reflect sensory function, and perhaps interoception and the subjective evaluation of the body’s
   condition.
   Support – This study was supported by the Physicians’ Services Incorporated, and the CRC program
   (K.D.D is a Canada Research Chair in Brain and Behaviour). KT was supported by the CIHR strategic
   training program Pain: M2C, Purdue Pharma, Ontario Graduate Scholarships, and the Crothers
   Fellowship.




                                                     - 66 -
53. Titley, Heather K. 1*; Heskin-Sweezie,Raquel1;Broussard, Dianne M. 1,2,3
    1
     Department of Physiology, University of Toronto; 2Division of Fundamental Neurobiology, Toronto
    Western Research Institute, University Health Network; 3Faculty of Medicine, Division of Neurology,
    University of Toronto
    CONSOLIDATION AND DISRUPTION OF NEWLY FORMED MEMORIES IN THE VESTIBULO-OCULAR REFLEX
    DOES NOT DEPEND ON THE ROTATIONAL FREQUENCIES DURING LEARNING AND TESTING
   The vestibulo-ocular reflex (VOR) exhibits motor learning that initially depends on synaptic plasticity in
   the cerebellar cortex. Learned decreases in VOR gain can be disrupted by rotation in darkness
   immediately following learning, but consolidate rapidly if the disruption stimulus is delayed. Disruption
   may simply reverse synaptic changes that have recently occurred, or it could reflect new learning at
   other sites. Similarly, rapid consolidation may involve altering the memory trace at the same synapses,
   or transferring it to a new set of synapses. Here, we induced motor learning in cats that wore
   miniaturizing goggles. We investigated the patterns of generalization for both disruption and
   consolidation, using a range of frequencies of rotation. During learning, the change was greatest when
   the training and test frequencies matched. Disruption generalized completely across frequencies,
   consistent with reversal of recent changes. Consolidation also generalized completely, consistent with
   stabilization of the memory at the original site.




                                                      - 67 -
54. Tsang, Eric W. *1,3; Hamani, Clement 2; Moro, Elena1; Mazzella, Filomena1; Poon Yu-Yan1; Lozano, Andres
    M2,3; Chen, Robert1,3
    1
     Divison of Neurology; 2Divison of Neurosurgery,University Heath Network, Toronto, ON, Canada;
    3
     Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    OSCILLATORY ACTIVITIES RECORDED FROM THE HUMAN PEDUNCULOPONTINE NUCLEUS REGION
    DURING VOLUNTARY MOVEMENTS
   We studied 7 patients with deep brain stimulation (DBS) electrodes (Medtronic 3387, contacts
   numbered 0 to 3) unilaterally implanted in the pedunculopontine nucleus region (PPNR) for the
   treatment of Parkinson’s disease (6) or progressive supranuclear palsy (1). Patients were studied 3-5
   days after surgery when the leads were externalized. Two patients were studied off dopaminergic
   medications (OFF) and 6 were studied on dopaminergic medications (ON). Local field potentials (LFPs)
   from the PPNR electrodes and scalp electroencephalogram (EEG) from Fz, Cz, C3, C4, Cp3, and Cp4
   electrodes were recorded while patients performed self-paced wrist extension or ankle dorsiflexion
   movements approximately once every 10 seconds. Epochs from 4 sec before and 3.5 sec (-4 to 3.5 sec)
   after movement onset were created. Bipolar montages were used for LFP (0-1, 1-2, and 2-3) whereas
   bipolar EEG were used to study different cortical regions (Midline, Cz-Fz; ipsilateral or contralateral
   motor region, C3/C4-Cz; ipsilateral or contralateral sensorimotor region, C3-Cp3 or C4-Cp4). We first
   examined the relative frequency spectra from 4 to 50Hz. Two frequency bands, 6-10Hz with peak at 8Hz
   and 14-30Hz with peak at 25Hz, were found to change with movements. Event-related
   desynchronization (ERD) and event-related synchronization (ERS) were examined for these two
   frequency bands. The DBS contact pair from each patient that was found to be at the PPNR based on
   post-operative MRI and showed biggest movement related changes in relative frequency was chosen.
   The results of ERD/ERS analyses were similar for ipsilateral, contralateral, wrist and ankle movements.
   PPNR showed greater ERD between 6 and 10Hz in the ON state compared to the OFF state with an
   average onset latency of -0.94 sec and ended at 2.9 sec. In OFF state, there was ERD between 14 and
   30Hz in both pre-movement and movement execution phases with an average onset latency of -1.4 sec
   and ended at 1.1 sec. In ON state, pre-movement ERS (14-30Hz) occurred at an average onset latency of
   -1.8 sec followed by ERD with an average onset of -0.2 sec and ended at 1.1 sec. Coherence analysis
   revealed coupling between PPNR and midline region (Cz-Fz) at 14-30Hz at approximately -2 sec to -0.5
   sec before movement onset. PPNR and ipsilateral sensorimotor regions (C3-Cp3 or C4-Cp4) coupling
   were found for the 6-10Hz band at -3.5 sec to 3.5 sec. These results indicated that the PPNR is active
   during both movement preparation and execution and involved two different oscillatory frequency
   bands. The midline and the ipsilateral sensorimotor cortical regions interact with the PPNR during both
   movement preparation and execution.




                                                     - 68 -
55. Weber, Alexander M*; Stanley, Elise F.
    Genetics and Development Division, Toronto Western Research Institute, University Health Network
    DETERMINING THE TRANSPORT RATE OF THE PRESYNAPTIC-TYPE CaV2.2 CALCIUM CHANNEL AT
    PHYSIOLOGICAL EXTERNAL Ca(2+) CONCENTRATIONS
   Calcium ions (Ca2+) are admitted into presynaptic nerve terminals through voltage gated calcium
   channels and diffuse to bind and activate the secretory vesicle discharge mechanism. Current research
   favors a highly ‘modal’ organization where the release sites are activated by one or a few closely
   apposed channels (Stanley, TINS 1997). To fully understand the nanophysiology of transmitter release
   site activation it is necessary to determine the rate of Ca2+ through individual channels at normal
   physiological external concentrations. We have previously determined this rate for the L-type, CaV1-
   type channels at 2 mM CaEXT as ~2.5 pS (Church and Stanley, 1996) but in this study we extend this
   analysis to the presynaptic-type, CaV2.2, channel. OBJECTIVES: To explore the relationship between
   CaV2.2 Ca2+ conductance and external Ca2+ across the physiological range. MATERIALS AND METHODS:
   Chick dorsal root ganglia neurons were isolated and single CaV2.2 channels were recorded using the
   cell-attached patch clamp technique using quartz electrodes. External Ca2+ ranged from 1 to 100 mM.
   Channel closing rates were reduced with R-Roscovitine. RESULTS: The CaV2.2 single channel
   conductance was moderately well described by a Michaelis-Menten fit with a Kd of ~5 mM. The
   conductance of the channel was ~2.5pS at 2 mM. CONCLUSION: Although CaV1-type channels exhibit a
   much larger conductance (~24 pS) than CaV2.2 (~12 pS) in high external Ba2+, the standard method of
   single channel analysis, their conductance with 2mM Ca2+EXT was indistinguishable. Our studies
   suggest that the single channel current at -40 mV is ~0.25 pA, a transport rate that is sufficient to
   saturate a Ca sensor within 25 nm (Stanley, Neuron 1993).




                                                   - 69 -
56. Wheeler, Anne L.*1,2; Lerch, Jason P.3; Sled, John G.3; Frankland, Paul W.1,2,4
    1
     Institute of Medical Science, University of Toronto; 2Program in Neurosciences and Mental Health, The
    Hospital for Sick Children, Toronto; 3The Mouse Imaging Center, The Hospital for Sick Children, Toronto;
    4
     Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
    CHRONIC COCAINE DURING ADOLESCENCE PRODUCES STRUCTURAL ABNORMALITIES IN THE BRAINS OF
    MICE
    When drug use is initiated during adolescence there are higher lifetime rates of drug use and faster
    progression to dependency than in people who begin in adulthood. This study investigates whether
    chronic cocaine use during this developmental time period has long-term effects on the structure of the
    mouse brain into adulthood. Fixed brain T2 weighted MRIs of 36 male offspring from a cross between
    C57BL/6NTacfBr [C57B6] and 129Svev [129] were acquired on a 7T scanner at 32 um isotropic
    resolution. Deformation-based morphometry (DBM), an automated technique for detecting anatomical
    differences between populations, was used to identify differences between animals treated with chronic
    cocaine or saline. Periadolescent and adult animals received cocaine (20mg/kg) or saline for 20 days and
    their brains were fixed 30 days afterwards. Morphometric abnormalities were apparent in animals
    treated with cocaine for 20 days during adolescence in several brain areas involved in processing drug
    reward as well as the cerebellum and white matter. No structural differences were apparent in the
    animals treated with cocaine during adulthood. These results suggest that adolescence is a time period
    in which the brain is vulnerable to structural abnormalities induced by cocaine exposure. Adolescent but
    not adult cocaine exposure has long-lasting effects on brain structure in mice.




                                                     - 70 -
57. Wong, Fiona K.*; Stanley, Elise F.
    Laboratory of Synaptic Transmission, Genes and Development, Toronto Western Research Institute,
    Toronto ON
    RAB3A INTERACTING MOLECULE (RIM) AND THE TETHERING OF PRESYNAPTIC TRANSMITTER RELEASE
    SITE-ASSOCIATED CAV2.2 CALCIUM CHANNELS
   Current studies suggest that presynaptic Cav2.2 calcium channels are attached to the transmitter
   release site within the active zone by a molecular tether. ‘Rab3a Interacting Molecule’ (RIM) is known
   to play a role in synaptic vesicle docking but has recently been proposed (Kiyonaka et al. Nature
   Neurosci. 2007) to also fulfill the channel tethering role. However, this suggestion is at variance with
   results published in our earlier study (Khanna et al., Neurosci. 2006). The main difference in these
   studies was that we failed to demonstrate co-immunoprecipitation (co-IP) of RIM and CaV2.2 whereas
   this was observed in the later study. OBJECTIVE: Three hypotheses were explored to account for the
   different conclusions between Kiyonaka et al and Khanna et al reports, respectively: 1) the use of
   different anti-RIM antibodies, mRIM and pRIM, 2) the stringency of the lysate solubilization buffer:
   digitonin or RIPA and, 3) the type of brain fraction used to generate the lysate: brain microsomes or
   purified synaptosome membrane. MATERIALS AND METHODS: Immunoprecipitation (IP) and Western
   blotting of avian brain lysates. RESULTS: We could not distinguish between the two studies based on
   antibody selectivity or solubilization buffers. While IP of Cav2.2 (Ab571) from whole brain lysate did co-
   IP RIM, the two proteins failed to co-IP from purified brain synaptosome membrane lysate using anti-
   CaV2.2 or either anti-RIM antibody. We also ruled out occlusion of the Ab571 binding site (CaV2.2 II-III
   loop) as two antibodies against a very different region of the channel (distal C terminal) also failed to co-
   IP RIM. CONCLUSIONS: While our findings are consistent with the existence of a Cav2.2/RIM protein
   complex in brain we conclude that this complex is not significant at presynaptic terminals. Thus, it is
   highly unlikely that RIM serves as a key scaffold protein for active zone Cav2.2 calcium channels.




                                                       - 71 -
58. Yiu, Adelaide P. 1,2*; Cole, Christina J. 1,3; Neve, Rachael L4; Westaway, David 5; Josselyn, Sheena A. 1,2,3
    1
     Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto;2Institute of Medical
    Sciences, University of Toronto;3Department of Physiology, University of Toronto; 4Molecular
    Neurogenetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital,
    Belmont, MA, USA; 5Prion Centre, University of Alberta, Edmonton, AB
    MEMORY DEFICITS IN ALZHEIMER’S DISEASE: A POSSIBLE ROLE OF CREB?
    Alzheimer’s disease (AD) is a neurodegenerative disorder that is initially characterized by mild memory
    impairments that progress to more global cognitive deficits, behavioral impairment and eventually
    death. As memory deficits are the core feature of AD, the search for novel treatments may benefit from
    building on basic research studying the molecular basis of normal memory formation. Amyloid plaques
    and neurofibrillary tangles serve as a criterion for postmortem diagnosis of the disease. As amyloid
    plaques consist mainly of a 40-42 amino acid peptide termed beta-amyloid peptide (Aβ), overproduction
    and accumulation of Aβ has been proposed to be a cause of AD. It is interesting that increased levels of
    Aβ disrupt the function of CREB (cAMP/Ca++ responsive element binding protein), a transcription factor
    that has been shown to be critical for normal memory formation. This suggests that some of the
    memory deficits in AD may be due to CREB dysfunction. Here we used a mouse model of AD to
    determine if increasing CREB function improves memory. TgCRND8 transgenic mice overexpress a
    human gene associated with familial AD and recapitulate key aspects of AD, including increased levels of
    Aβ and memory deficits. TgCRND8 mice show lower phosphorylated CREB (activated form) levels in the
    CA1 region of the hippocampus after novel spatial exploration and Morris Water Maze (MWM) test,
    both behavior tests which induce CREB activation. We, and others, have shown that these transgenic
    mice show robust spatial memory deficits, as assessed by the MWM. We used viral mediated gene
    transfer techniques to acutely increase CREB function directly in the hippocampus, targeting the CA1
    specifically of transgenic and wild-type littermate control mice to rescue this memory deficit. Our results
    show that increasing CREB partially rescues the spatial memory deficits in this AD mouse model. These
    results may serve as an initial step towards developing novel treatment strategies to reverse or delay
    the early memory deficits of AD.




                                                         - 72 -
59. Yong-Kee, Christopher J.*; Hanif, Asad; Nash, Joanne E;
    Department of Cell and Systems Biology , University of Toronto
    IDENTIFICATION OF CONVERGENT SUB-CELLULAR MECHANISMS INDUCED BY CELL STRESS DURING
    PARKINSON’S DISEASE
   Parkinson’s disease (PD) is the most common movement disorder affecting 1-2% of the population over
   the age of 60. Both genetic and idiopathic Parkinson’s disease is thought to be caused by individual
   cellular abnormalities such as oxidative stress, mitochondrial dysfunction, ubiquitin-proteasome system
   (UPS) malfunction, and more recently, lysosome inhibition. Increasing evidence has revealed that each
   of these individual abnormalities can interact to induce cellular death. Indeed, we have previously
   shown that inhibition of mitochondria, UPS and lysosome function interact to potentiate reductions in
   cell viability. Given that multiple mechanisms are responsible for cell death in PD, and that these
   pathways synergise, development of an effective neuroprotective strategy requires elucidation of how
   and when these sub-cellular mechanisms interact. To this end, we utilized the dopaminergic
   neuroblastoma cell line, SH-SY5Y, and determined the convergence of sub-cellular mechanisms and the
   changes in these mechanisms over time with the use of immunocytochemistry and molecular probes.
   SH-SY5Y cells were exposed to EC50 concentrations of toxins which recapitulate cell death in PD –
   dopamine hydrochloride (30 μM) (reactive oxygen species), naphthazarin (2.17 μM) (lysosome damage),
   proteasome inhibitor (PSI) (80 μM), and rotenone (40 μM) (mitochondrial complex 1 inhibition). Six,
   twelve and twenty four hours following exposure to toxins, α-synuclein, SDHA, caspase-3 and ubiquitin
   levels were examined by immunocytochemistry. Naphthazarin, rotenone and PSI increased ubiquitin
   expression after 6 hours. In addition, rotenone caused the co-localization of mitochondria and ubiquitin
   after 12 hours. Interactions of individual mechanisms were further revealed after 24 hours when PSI
   induced the co-localization of mitochondria and ubiquitin. To monitor changes in organelle function
   over time, molecular probes were added to SH-SY5Y cells after a 6, 12 and 24 hour toxin incubation
   period. Evidence of convergent mechanisms were seen when proteasome inhibition resulted from
   rotenone toxicity, and when PSI exposure caused lysosomal inhibition. These studies identify the
   interactions between different sub-cellular mechanisms and changes in organelle function in response
   to conditions of cell stress over time. It is necessary to determine the convergent mechanisms in order
   to prevent the cascade of mechanisms that lead to cell death. In doing so, therapeutic targets will be
   discovered which will prevent cell death during PD.




                                                    - 73 -
60. Zavalishina, L. 1, 2 *; Safir, A.2; Yonekura, N.1 ; Logan, R. 1; Zhang, L.1, 3; Eubanks, J. 1,2,3
    1
     Division of Genetics and Development , Toronto Western Research Institute, Toronto; 2Department of
    Physiology; 3Institute of Medical Science, Surgery, Faculty of Medicine, University of Toronto.
    MBD2, ANOTHER METHYL-CPG-BINDING PROTEIN, CONTRIBUTES TO AUTISM-LIKE BEHAVIOURAL
    PHENOTYPE IN MICE
   The importance of epigenetic influence in variety of diseases and behaviors is becoming increasingly
   clear. Methyl-CpG- binding proteins (MBP) such as MeCP2, MBD1-MBD3, recruit transcriptional co-
   repressor molecules to methylated regions of the genome which modify surrounding chromatin and
   generally silence transcription. It is now clear that these factors participate in neural development and
   functional maintenance, as mutations in MeCP2 cause the autism spectrum disorder of Rett syndrome,
   the deficiency of MBD1 in mice leads to autism-like behavioural deficits, and early embryonic neural
   development is aberrant in mice lacking MBD3. To date, however, the role of MBD2 in regulating brain
   function and behaviour remains largely unexamined. To begin elucidating whether and how MBD2
   influences neural function, I compared the performance MBD2-null mice to wild-type mice in a battery
   of behavioral tests, and compared their somatosensory and hippocampal electroencephalographic (EEG)
   activity in vivo during exploration, sleep and immobile states, and the magnitude of hippocampal
   synaptic plasticity in vitro. The results of these assays indicate that MBD2-null mice display a heightened
   anxiety-like behavior, diminished explorative activity, and progressively decreased activity levels
   compared to wild-type mice. However, these behavioral differences were not paralleled by
   neurophysiological impairments, as long-term potentiation at MBD2-null CA1 synapses was preserved,
   and analysis of the EEG patterns of MBD2-null mice failed to identify significant differences from wild-
   type. Specifically, MBD2 null mice display normal low amplitude desynchronized basal activity in
   hippocampus, clear theta activity of normal frequency during exploration, the lack of abnormal slow
   spike and wave discharges during immobile and sleep stages, and preserved delta-like activity and sharp
   waves during sleep in cortex and hippocampus, respectively. Taken together, these data indicate that
   the loss of MBD2 is sufficient to induce a state of heightened anxiety-like behavior in mice without
   introducing gross deficits in hippocampal or cortical neurophysiology.




                                                     - 74 -
61. Zhang, W.-J.*1,2; Lau, A.1; Tymianski, M.1,2
    1
     Department of Fundamental Neurobiology, Toronto Western Research Institute, Toronto; 2Department
    of Physiology, Faculty of Medicine, University of Toronto
    PSD-95 INHIBITOR, TAT-NR2B9C, ATTENUATES BEHAVIOUR DEFICITS FOLLOWING TRAUMATIC BRAIN
    INJURY IN RATS.
   Traumatic brain injury (TBI) is the leading cause of death and disability for Canadians under the age of
   45. TBI occurs at two levels; there is an immediate CNS tissue disruption (primary injury), as well as
   further damage mediated by complex mechanisms triggered by the primary insult (secondary injury)
   leading to anatomical and neurological brain damage. Among the secondary injury mechanisms is the
   formation of the reactive nitrogen species nitric oxide (NO), which leads to protein nitration, cell
   dysfunction and death. Our lab has developed a peptide, Tat-NR2B9c, which inhibits the interactions of
   NMDA glutamate receptors and the scaffolding postsynaptic density protein PSD-95. This peptide
   reduces NO formation, decreases damaging neuronal nitration and assists in neuroprotection in both in
   vitro and in vivo models of ischemic brain damage as well as TBI in vitro. However, its therapeutic effects
   for TBI in vivo have not been previously explored. Therefore, the aim of this study was to investigate the
   effects of TAT-NR2B9c on behaviour deficits following TBI in rats by way of the Beam-Walk and Rota-Rod
   paradigms. Sprague-Dawley male rats were trained for the Beam-Walk and Rota-Rod tests 24hrs before
   surgery and baseline behaviour testing were performed between the surgery and the injury time points.
   Following surgery, the animals were divided into two treatment groups and they were administered
   either TAT-NR2B9c or saline control 30 minutes prior to receiving a moderate level of fluid percussion
   injury (~2.5atm). Afterwards, all rats were evaluated on the Beam-Walk and Rota-Rod tasks 24hrs,
   48hrs, and 72hrs following the injury time point. Results show that the injury produced significant
   deficits in the ability of the animals to perform the Beam-Walk and Rota-Rod tests. However, there was
   a significant improvement in TAT-NR2B9c treated rats compared to control animals at the 24hrs time
   point following injury for the Beam-Walk task and for all time points following injury for the Rota-Rod
   task. Also, at the 24hrs time point, TAT-NR2B9c reduced the number of falls on the Beam-Walk by 70%.
   Performance on the Beam-Walk and Rota-Rod tests also improved gradually throughout the time points
   in all rat groups. These findings demonstrate that the Beam-Walk and Rota-Rod tests are sensitive tests
   for assessing behavioural deficits following TBI and that TAT-NR2B9c is an effective therapy for
   improving motor function in rats with TBI. These results also suggest performance on the Beam-Walk
   and Rota-Rod improves as time progresses and this may be due to innate recovery and learning and
   memory in all rat groups.




                                                     - 75 -
62. Zurek, A.A. 1*; Saab, B.J. 2,3 ; Orser, B.A.1
    1
     Departments of Physiology , Faculty of Medicine, University of Toronto; 2Samuel Lunenfeld Research
    Institute, Mount Sinai Hospital, Toronto; 3Department of Molecular Genetics, University of Toronto
    PERSISTENT MEMORY IMPAIRMENT FOLLOWING ISOFLURANE ANESTHESIA
   Memory blockade during surgery is an essential component of the anesthetic state. However, persistent
   memory deficits are a common adverse effect of anesthesia and surgery. Animal models are required to
   understand the underlying mechanism of postoperative memory impairment and to identify treatment
   strategies. The goal of this study was to employ a behavioral animal model that does not depend on
   aversive conditioning to characterize post-anesthetic memory performance at multiple time points.
   C57Bl6/129SvEv mice were exposed to isoflurane (1 hour, 1 L/min, 1.3%;1 MAC) or vehicle in a heated
   (35°C), air-tight chamber. Mice were trained in an object recognition paradigm either 1 hour or 24 hours
   following anesthesia. Following habituation to the context, mice explored two identical objects for 10
   minutes. One hour following training, the mice were re-exposed to the context and one of the
   previously shown objects and a novel object. Memory of the familiar object was measured as preference
   for the novel object (percent of time spent with novel object). Mice were subjected to the elevated plus
   maze and balance beam test to measure anxiety levels and motor performance. Gas chromatography
   was used to measure levels of isoflurane in the brains of animals sacrificed 1 hour or 24 hours after
   anesthesia. Mice treated with isoflurane demonstrated impaired memory on an object recognition task
   acquired one hour after anesthesia. The mice trained 1 hour after anesthesia demonstrated significantly
   reduced preference for the novel object in comparison to controls (42 ±5.12% vs. 62 ± 5.12%, p<0.05).
   Importantly, mice exhibited a similar deficit even when the mice are trained 24 hours following the
   anesthetic episode (47 ± 5.30% vs. 65 ±3.95%, p<0.05). Only trace concentrations of isoflurane were
   detected in the brain (0.0095 ± 0.0006 % isoflurane) at 24 hours, indicating that deficits in learning and
   memory persist long after the volatile anesthetic has been metabolized. There were no differences in
   motor performance or anxiety scores in isoflurane-treated versus control mice at 1 hour following
   anesthesia. Object recognition can be used to reveal memory deficits after anesthesia. A brief exposure
   to a clinically relevant concentration of isoflurane impairs learning and memory up to 24 hours. In
   contrast to paradigms that rely on the perception of a painful stimulus(e.g. fear conditioning), the ability
   to perform repeated measures with object recognition allows within subject testing. This paradigm can
   be used to characterize the time-course of post-anesthetic deficits and test pharmacological
   interventions that may be used to treat the deficits.




                                                      - 76 -

								
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