M. Zhuo
Dr. Zhuo
Contact Information:
Phone: (416) 978-4018 (office)
Phone 2: (416) 978-8719 (lab)
Fax: (416) 978-4940
Email: min.zhuo@utoronto.ca
Webpage: individual.utoronto.ca/zhuo/
Address: Department of Physiology
Medical Sciences Building, Room 3342
University of Toronto
Toronto, Ontario M5S 1A8

ACADEMIC STATUS
Departmental Status: Full Professor; Michael Smith Chair in Neuroscience and Mental Health; Canada Research Chair in Pain and Cognition

Degrees: Ph.D 1992

Affiliations: University of Toronto Centre for the Study of Pain

Courses Taught: Molecular basis of behaviors

RESEARCH
Research Division: Brain Research and Integrated Neurophysiology B.R.A.I.N. Platform

Research Interests: Genetic models for neurological and psychiatric diseases; Synaptic transmission and regulation Synaptic plasticity: long-term potentiation and depression; Physiological and athological related central plastic changes: synaptic responses and action potentials; Memory, emotion, sensation, stress and cortical reorganization; Alzheimer’s disease, aging and persistent pain

Keywords: Synaptic plasticity, cortical plasticity, sensory, memory, emotion, spinal cord, hippocampus, cortex, pain, pleasure, chronic pain, fear, aging, Schizophrenia, Alzheimer’s disease

Detailed Description:

We are interested in the cellular mechanisms of synaptic transmission and plasticity in the central nervous system and functional implications of such plastic changes. Long-term plastic changes in synaptic transmission are believed to contribute to information storage in the brain. The laboratory employs a combination of genetic, electrophysiological, pharmacological and behavioral approaches. At the single neuron level, whole-cell patch clamp recordings of synaptic responses are made from single neurons in brain and spinal cord slices. At the system level, neuronal evoked responses in intact or freely moving animals are performed to study neuronal plasticity in emotional learning, persistent pain and drug addiction. At the behavioral level, a combination of pharmacological and genetic approaches in mice (genetic mutant mice) allows us to study molecular mechanisms of emotional fear memory and pain.

The current research projects are: (1) molecular and synaptic mechanisms for emotional fear memory; (2) glutamatergic synaptic transmission and regulation at sensory synapses; (3) genetic manipulation of NMDA NR2B receptors in the anterior cingulate cortex and its functional implications such as pain and pleasure; (4) aging related changes in central plasticity and behavioral learning. We believe that these studies performed at different levels, from neuron to behavior, will help us to understand the mechanisms of central synaptic plasticity, in particular those underlying fear memory and persistent pain.

METHODS USED
Procedures: Behavioural tests, in-vitro electrophysiology, in-vivo electrophysiology

EQUIPMENT USED
Amplifier (Molecular Device Multiclamp 7000A; Molecular Device Axopatch 200B), analytical balances (Mettler Toledo, AB54-S), benchtop centrifuge, confocal microscope (Olympus, Fluoview 1000), Cryostat (Leica, CM3050S), Digidata (Molecular device, 1322 A), fluorescence microscope (Olympus, BX51), fresh tissue sectioning systems (Wanner instrument, vibratome 1000), low and ultralow freezers, micropipette puller (Sutter Instrument Company, P-97), motorized micromanipulators (Sutter Instrument Company, MP-285), pneumatic picopump (PV820, WPI), pressure osmometer (Vapro 5520), ProBlot hybridization oven, setups for electropherosis, stimulator (Grass, S88), stirrer/hot plate, water baths

SAMPLE PUBLICATIONS AND ABSTRACTS
Click on Link to PubMed

Li, P., and Zhuo, M . (1998). Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature 393, 695-698.

Li, P., Kerchner, G. A., Sala, C., Wei, F., Huettner, J. E., Sheng, M., and Zhuo, M . (1999). AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses. Nat Neurosci 2, 972-977.

Li, P., Wilding, T. J., Kim, S. J., Calejesan, A. A., Huettner, J. E., and Zhuo, M . (1999). Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature 397, 161-164.

Tang, Y. P., Shimizu, E., Dube, G. R., Rampon, C., Kerchner, G. A., Zhuo, M. , Liu, G., and Tsien, J. Z. (1999). Genetic enhancement of learning and memory in mice. Nature 401, 63-69.

Kerchner, G. A., Wang, G. D., Qiu, C. S., Huettner, J. E., and Zhuo, M. (2001). Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism. Neuron 32, 477-488.

Wei, F., Wang, G. D., Kerchner, G. A., Kim, S. J., Xu, H. M., Chen, Z. F., and Zhuo, M . (2001). Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nat Neurosci 4, 164-169.

Wei, F., Qiu, C. S., Kim, S. J., Muglia, L., Maas, J. W., Pineda, V. V., Xu, H. M., Chen, Z. F., Storm, D. R., Muglia, L. J., and Zhuo, M. (2002). Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. Neuron 36, 713-726.

Wei, F., Qiu, C. S., Liauw, J., Robinson, D. A., Ho, N., Chatila, T., and Zhuo, M . (2002). Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci 5, 573-579.

Zhao, MG, Toyoda, H, Lee, YS, Wu ,LJ, Ko, SW, Zhang, XH, Jia, Y, Shum, F, Xu, H, Li, BM, Kaang, BK and Zhuo, M. (2005). Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron 47, 859-872.

Wang H, Wu LJ, Kim SS, Lee FJ, Gong B, Toyoda H, Ren M, Shang YZ, Xu H, Liu F, Zhao MG, Zhuo M . (2008) FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron , 59:634-647.

Vecsey CG, Baillie GS, Jaganath D, Havekes R, Daniels A, Wimmer M, Huang T, Brown KM, Li XY, Descalzi G, Kim SS, Chen T, Shang YZ, Zhuo M , Houslay MD, Abel T. (2009) Sleep deprivation impairs cAMP signalling in the hippocampus. Nature 461:1122-1125.

Slutsky I, Abumaria N, Wu LJ, Huang C, Zhang L, Li B, Zhao X, Govindarajan A, Zhao MG, Zhuo M , Tonegawa S, Liu G (2010) Increasing synaptic density and enhanced memory by brain magnesium. Neuron 65:165-177.

Li XY, Ko HG, Chen T, Descalzi G, Koga K, Wang H, Kim SS, Shang Y, Kwak C, Park SW, Shim J, Lee K, Collingridge GL, Kaang BK, Zhuo M. (2010)  Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex. Science 330:1400-1404.

Wang H, Xu H, Wu LJ, Kim SS, Chen T, Koga K, Descalzi G, Gong B, Vadakkan KI, Zhang X, Kaang BK, Zhuo M. (2011) Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain. Science Translational Medicine , ;3(65):65ra3 (Comment in: Nat Rev Drug Discov. 2011 Mar;10(3):176).

Reviews:

Zhuo, M. (2000). Silent glutamatergic synapses and long-term facilitation in spinal dorsal horn neurons. Prog Brain Res 129, 101-113.

Zhuo, M. (2002). Glutamate receptors and persistent pain: targeting forebrain NR2B subunits. Drug Discov Today 7, 259-267.

Zhuo, M. (2004). Central plasticity in pathological pain. Novartis Found Symp 261, 132-145; discussion 145-154.

Zhuo, M. (2005). Canadian Association of Neuroscience review: Cellular and synaptic insights into physiological and pathological pain. EJLB-CIHR Michael Smith Chair in Neurosciences and Mental Health lecture. Can J Neurol Sci 32, 27-36.

Zhuo, M . (2008) Cortical plasticity and chronic pain. Trends Neuroscience, 31:199-207


PRESENT TRAINEES
Xiangyao Li
Tao Chen
Kohei Koga
Shuang Qiu
Anett Shumacher
Giannina Descalzi
Su-eon Sims
Heather Kang
Flora Nasri
Kaori Yamada 
Opening positions for graduate and postdoc fellows