6875 Boulevard Lasalle
Researcher, Douglas Institute
Associate Professor, Department of Psychiatry, McGill University
Glutamate synapses and psychiatric disorders
Psychiatric disorders comprise a wide range of diseases (e.g. depression, schizophrenia, dementia) that exhibit abnormal thoughts, moods and behaviors and account for 12% of the global burden of all diseases 239. Pharmacological intervention for psychiatric disorders used to rely largely on drugs that manipulate monoaminergic transmission. Recently reported antidepressant and antipsychotic effects of drugs targeting glutamatergic transmission have raised a lot of interest in the field of psychiatry to understand the role of glutamate, the most commonly found excitatory neurotransmitter, in the neuropathology of psychiatric disorders. In addition, glutamatergic transmission is known to be highly changeable in an experience-dependent manner. Plastic properties of glutamate synapses, including long-term potentiation (LTP) and depression (LTD), have been regarded as cellular substrates for learning and memory. Malfunctioning of glutamatergic transmission could thus underlie cognitive impairment that is commonly associated with psychiatric disorders.
In this research program, we investigate mechanisms underlying changes in glutamatergic transmission in animal models that mimic psychopathologies of psychiatric disorders. These studies are primarily performed in the hippocampus, a brain region that not only is crucial in various cognitive functions, but also is affected in many psychiatric disorders. Findings from this research program will help us understand the contribution of malfunctioning glutamatergic transmission to psychiatric disorders and provide rationale and therapeutic targets for treating these disorders.
Maternal care differentially affects neuronal excitability and synaptic plasticity in the dorsal and ventral hippocampus.
Nguyen HB, Bagot RC, Diorio J, Wong TP*, Meaney MJ*. (*corresponding authors)
Neuropsychopharmacology. 2015 Jun;40(7):1590-9.
A longitudinal study of stress-induced hippocampal volume changes in mice that are susceptible or resilient to chronic social defeat.
Tse YC, Montoya I, Wong AS, Mathieu A, Lissemore J, Lagace DC, Wong TP.
Hippocampus. 2014 Sep;24(9):1120-8.
Impaired adrenergic-mediated plasticity of prefrontal cortical glutamate synapses in rats with developmental disruption of the ventral hippocampus.
Bhardwaj SK, Tse YC, Ryan R, Wong TP, Srivastava LK.
Neuropsychopharmacology. 2014 Dec;39(13):2963-73.
Prenatal immune activation interacts with stress and corticosterone exposure later in life to modulate N-methyl-D-aspartate receptor synaptic function and plasticity.
Burt MA, Tse YC, Boksa P, Wong TP.
Int J Neuropsychopharmacol. 2013 Sep;16(8):1835-48.
Opposing alterations in excitation and inhibition of layer 5 medial prefrontal cortex pyramidal neurons following neonatal ventral hippocampal lesion.
Ryan RT, Bhardwaj SK, Tse YC, Srivastava LK, Wong TP.
Cereb Cortex. 2013 May;23(5):1198-207.
Knockdown of prodynorphin gene prevents cognitive decline, reduces anxiety, and rescues loss of group 1 metabotropic glutamate receptor function in aging.
Ménard C, Tse YC, Cavanagh C, Chabot JG, Herzog H, Schwarzer C, Wong TP*, Quirion R*. (*corresponding authors)
J Neurosci. 2013 Jul 31;33(31):12792-804.
Maternal care influences hippocampal N-methyl-D-aspartate receptor function and dynamic regulation by corticosterone in adulthood.
Bagot RC, Tse YC, Nguyen HB, Wong AS, Meaney MJ, Wong TP.
Biol Psychiatry. 2012 Sep 15;72(6):491-8.
Modulation of synaptic plasticity by stress hormone associates with plastic alteration of synaptic NMDA receptor in the adult hippocampus.
Tse YC, Bagot RC, Hutter JA, Wong AS, Wong TP.
PLoS One. 2011;6(11):e27215.
Hippocampal long-term depression is required for the consolidation of spatial memory.
Ge Y, Dong Z, Bagot RC, Howland JG, Phillips AG, Wong TP*, Wang YT*. (*corresponding authors)
Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16697-702.
Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment.
Wong TP, Howland JG, Robillard JM, Ge Y, Yu W, Titterness AK, Brebner K, Liu L, Weinberg J, Christie BR, Phillips AG, Wang YT.
Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11471-6.
NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo.
Liu Y, Wong TP, Aarts M, Rooyakkers A, Liu L, Lai TW, Wu DC, Lu J, Tymianski M, Craig AM, Wang YT.
J Neurosci. 2007 Mar 14;27(11):2846-57.
Nucleus accumbens long-term depression and the expression of behavioral sensitization.
Brebner K*, Wong TP*, Liu L, Liu Y, Campsall P, Gray S, Phelps L, Phillips AG, Wang YT. (*co-first authors)
Science. 2005 Nov 25;310(5752):1340-3.
Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity.
Liu L*, Wong TP*, Pozza MF, Lingenhoehl K, Wang Y, Sheng M, Auberson YP, Wang YT. (*co-first authors)
Science. 2004 May 14;304(5673):1021-4.
Loss of presynaptic and postsynaptic structures is accompanied by compensatory increase in action potential-dependent synaptic input to layer V neocortical pyramidal neurons in aged rats.
Wong TP, Marchese G, Casu MA, Ribeiro-da-Silva A, Cuello AC, De Koninck Y.
J Neurosci. 2000 Nov 15;20(22):8596-606.
Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes.
Wong TP, Debeir T, Duff K, Cuello AC.
J Neurosci. 1999 Apr 1;19(7):2706-16.
Dr. Tak Pan Wong moved to Montreal from Hong Kong in 1995 to pursue his PhD study under the supervision of Dr. Claudio Cuello and Dr. Yves De Koninck at McGill University. His postdoctoral training in the laboratory of Dr. Yu Tian Wang at University of British Columbia examined the molecular mechanism of synaptic plasticity. Since 2006, he has established his research laboratory at Douglas Institute to investigate the contribution of synaptic plasticity to rodent behavioral changes that are related to psychopathology of psychiatric disorders.
FRSQ Research Scholar (senior)
FRSQ Research Scholar Award
NARSAD Young Investigator Award
The National Alliance for Research on Schizophrenia and Depression (NARSAD) created the Young Investigator Award to help the most promising scientists who are now entering research to generate pilot data necessary for larger grants.
FRSQ Research Scholar Award
Undergraduate student: Shihan Chen, Julia Yu
MSc student: Brittany Zhang
PhD student: Chelsea Cavanagh, Huy-Binh Nguyen
Technician: Alice Wong
Postdoctoral fellow: Dr. Zhiling Guo
Research Associate: Dr. Yiu Chung Tse, Dr. Joelle Lopez
Antidepressive effects of targeting ELK-1 signal transduction. Nat Med. 2018;24(5):591-597.
Generalization of Conditioned Auditory Fear is Regulated by Maternal Effects on Ventral Hippocampal Synaptic Plasticity. Neuropsychopharmacology. 2018;43(6):1297-1307.
Morphological and functional changes in the preweaning basolateral amygdala induced by early chronic stress associate with anxiety and fear behavior in adult male, but not female rats. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:25-37.
Primary Blast-Induced Changes in Akt and GSK3β Phosphorylation in Rat Hippocampus. Front Neurol. 2017;8:413.
A Rapid Pipeline to Model Rare Neurodevelopmental Disorders with Simultaneous CRISPR/Cas9 Gene Editing. Stem Cells Transl Med. 2017;6(3):886-896.
Inhibiting tumor necrosis factor-α before amyloidosis prevents synaptic deficits in an Alzheimer's disease model. Neurobiol Aging. 2016;47:41-49.
Maternal care differentially affects neuronal excitability and synaptic plasticity in the dorsal and ventral hippocampus. Neuropsychopharmacology. 2015;40(7):1590-9.
Loss of dysbindin-1, a risk gene for schizophrenia, leads to impaired group 1 metabotropic glutamate receptor function in mice. Front Behav Neurosci. 2015;9:72.
Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus. Biol Psychiatry. 2015;77(6):513-25.
Impaired adrenergic-mediated plasticity of prefrontal cortical glutamate synapses in rats with developmental disruption of the ventral hippocampus. Neuropsychopharmacology. 2014;39(13):2963-73.
dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients. Transl Psychiatry. 2013;3:e338.