Research InterestsPresynaptic and postsynaptic mechanisms underlying excitatory synaptic transmission in the mammalian central nervous system.
Degrees: Ph.D. (1993)
Affiliations: The Program in Neurosciences & Mental Health, SickKids Research Institute
Courses Taught: PSL452/1052; JYG1555 (Director); PSL450;
Keywords: Voltage-gated calcium and potassium channels/ Neurotransmitter release and replenishment/ Glutamate receptors/ Auditory brainstem.
Detailed Description: Communication between neurons in the central nervous system is achieved primarily through highly specialized anatomical structures, known as chemical synapses. The efficacy of synaptic transmission largely lies within the ability of presynaptic terminals to release small vesicles containing neurotransmitters and the ability of postsynaptic receptors to respond to the released substances. Using a giant synapse, namely the calyx of Held, in the mouse/rat auditory brainstem as a model system, we employ a number of biophysical approaches (i.e. paired patch-clamping, optical fluorescent imaging and photolysis in living brainstem slices) as well as pharmacological, immunochemical and molecular biological techniques to study critical elements for synaptic strength, fidelity and gain control in response to high-frequency stimuli. Our ultimate goal is to elucidate the cellular and molecular mechanisms underpinning synaptic transmission and developmental plasticity.
Our laboratory has two main research areas:
1. Presynaptic developmental plasticity: We are particularly interested in morphological and functional remodeling in the spatiotemporal relationship between Ca2+ influx via voltage-gated Ca2+ channels (VGCCs) and transmitter release as well as Ca2+-dependent replenishment of the readily-releasable pool of synaptic vesicles;
2. Activity-dependent gating switch of postsynaptic glutamate receptors. The neurotransmission at the calyx of Held synapse undergoes profound acceleration in speed and upregulaton in fidelity after the onset of functional hearing at postnatal day 10-12. We are interested in studying how synaptic activity influences glutamate receptor subunit composition, gating and trafficking to boost high-fidelity auditory neurotransmission in vitro and in vivo.
Brain Slice, endothelial cells, neurons, electrophysiology, gene expression analysis, immunohistochemistry, immunocytochemistry, in vitro electrophysiology, in vivo electrophysiology, intracellular injection, patch clamp, qRT-PCR, RT-PCR, voltage clamp, western blot
Amplifier, analytical balances, benchtop centrifuge, calcium imaging system, confocal microscope, culture hood, culture incubators, cryostat, deconvolution fluorescence microscope, digidata, digital microscope, dissecting microscope, electrophysiology rig, fluorescence microscope, fresh tissue sectioning systems, micropipette puller, motorized micromanipulators, stimulator, stirrer/hot plate, vibratome, water baths, blotting apparatus
(1) Mr. Steve Lesperance, Ph.D. Student (09/2008-present)
Project: Activity-dependent gating switch of AMPARs at the developing calyx of Held synapse.
(2) Mr. Ankur Bodalia, Ph.D. Student (09/2013-present)
Project: Developmental plasticity at the calyx of Held synapse.
(3) Mr. Derek Howard, MSc Student (09/2012-present)
Project: Activity-dependent plasticity in excitability at the developing calyx of Held synapse.
(4) Dr. Ariel Avila, Postdoctoral Fellow (07/2014-present)
Project: Functional and morphological remodeling of central synapses.
(5) Dr. Adam Fekete, Postdoctoral Fellow (06/2013-present)
Project: Coupling Ca2+ channels to the docking and fusion of synaptic vesicles.
(6). Dr. Amy (Yi-Mei) Yang, Postdoctoral Research Associate (01/2013-present)
Project: Regulation of the fidelity of neurotransmission at the calyx of Held synapse.
Within the Department of Physiology:
Drs. Michael Salter, William Trimble, Zhengping Jia & Robert Harrison
Outside the Department of Physiology:
Dr. John Roder-Mount Sinai Hospital;
Dr. Peter St George-Hyslop-University of Toronto;
Drs. Paul Worley & Richard Huganir-John Hopkins University, USA;
Dr. Hiruhiko Bito-University of Tokyo, Japan
Dr. Zhuan Zhou-Peking University, China
Dr. Jiuping Ding-Huazhong University of Science and Technology
PRESENT GRANT COMMITTEES SERVED ON
Foundation Scheme Stage I College of Reviewers
Publications and Awards