Department of Physiology and Biophysics
Professor of Physiology & Neuroscience
Cytoskeleton and cell motility; Molecular and Cellular Biology; Molecular Basis of Disease; Neurobiology; Neurodegenerative disorders; Neuropharmacology; Pathophysiology; Signal Transduction
My lab is focused on studying the mechanisms underlying the regulation of ligand-gated ion channels and synaptic transmission, and its implication in various brain disorders.
Information processing in the central nervous system (CNS) is achieved by the interplay between chemical and electrical signals. Neuromodulators (e.g. dopamine, serotonin, acetylcholine, and corticosteroid stress hormones) influence CNS functions by regulating ion channels, which can produce short-term changes in membrane excitability and long-term changes in synaptic plasticity. Dysfunctions of these neuromodulators in specific brain regions have been implicated in the pathogenesis of various mental disorders, including schizophrenia, depression and Alzheimer’s disease. One of our major goals is to understand how these neuromodulators regulate ligand-gated ion channels and synaptic transmission in prefrontal cortex, a key region controlling cognition and emotion.
Neuromodulators exert their actions through G protein-coupled receptors or nuclear hormone receptors. These receptors link to various intracellular signaling cascades, which potentially influence different ion channels in a specific and coordinated manner. We use a combination of multiple approaches to reveal signal transduction pathways mediated by neuromodulators. Specifically,
• Electrophysiological techniques, such as whole-cell patch-clamp recordings in cultured neurons and brain slices, are used to characterize the effect of neuromodulators on glutamate and GABA receptor channels and synaptic transmission.
• Biochemical and pharmacological approaches are used to identify the signaling molecules linking neuromodulators and channels.
• Molecular and immunocytochemical techniques are used to detect the expression, localization and trafficking of receptors, ion channels and signaling components in neurons.
• Animal models carrying mutant genes for neurological disorders are used to examine the aberrant neuromodulator actions and their causal link to behavioral deficits in these pathological conditions.
Our studies will provide knowledge on the molecular and cellular mechanisms underlying the regulation of synaptic functions by neuromodulators, which is important for mental health and diseases.