Keywords:

Neurotransmitters, Neuropeptides, Synaptic transmission and plasticity, Ion channels, Learning and memory, Synaptogenesis, Neurodegenerative disease, Epilepsy, Anxiety, Hippocampus, Entorhinal Cortex, Interneuron, Patch-clamp, Electrophysiology

Education/Training:

We use a variety of techniques including electrophysiology, immunocytochemisty, imaging, tissue culture, molecular biology and in vivo physiology and animal models to study the functional changes of the central nervous system in physiological and pathological conditions. Our current research interests include:

1. Modulation of synaptic transmission and plasticity in the hippocampus and entorhinal cortex. Using infrared video microscopy and patch-clamp recording techniques, we are able to record the synaptic activity or ion channel currents from visually identified neurons in slices. The synaptic activities and ion channel functions are modulated by numerous modulators including neurotransmitters and neuropeptides. We are exploring the underlying cellular and molecular mechanisms using molecular biology, pharmacology and transgenic animal models.
2. The functional changes of neurons induced by the neurotransmitters and neuromodulators are likely to be responsible for a variety of physiological functions such as learning and memory or clinical disorders including epilepsy, anxiety and neurodegenerative diseases. We are using in vivo disease models to study the roles of these neuromodulators in these clinical disorders. Our research would likely to provide clues at the molecular and cellular levels to treat neurological diseases.

Selected Research Papers:

1. Deng PY, Xiao Z, Yang C, Rojanathammanee L, Grisanti L, Watt J, Geiger JD, Liu R, Porter JE, Lei S. GABAB receptor activation inhibits neuronal excitability and spatial learning in rat entorhinal cortex by activating two-pore domain K+ channels. Neuron 63: 230-243, 2009
2. Deng PY, Xiao Z and Lei S. Distinct Modes of Modulation of GABAergic Transmission by Group I Metabotropic Glutamate Receptors in Rat Entorhinal Cortex. Hippocampus (in press)
3. Xiao Z, Deng PY, Yang C, Lei S. Modulation of GABAergic Transmission by Muscarinic Receptors in the Entorhinal Cortex of Juvenile Rats. Journal of Neurophysiology 102:659-669, 2009
4. Xiao Z, Deng PY, Rojanathammanee L, Yang C, Grisanti L, Permpoonputtana K, Weinshenker D, Doze VA, Porter JE and Lei S. Noradrenergic depression of neuronal excitability in the entorhinal cortex via activation of TREK-2 K+ channels. Journal of Biological Chemistry 284: 10980-10991, 2009
5. Deng PY, Lei S. Serotonin increases GABA release and depresses epilepsy in the entorhinal cortex. Molecular and Cellular Neuroscience 39:273-284, 2008
6. Lei S, Deng PY, Porter JE, Shin HS. Adrenergic Facilitation of GABAergic Transmission in Rat Entorhinal Cortex. Journal of Neurophysiology 98:2868-2877, 2007
7. Deng PY, Poudel SKS, Rojanathammanee L, Porter JE, Lei S. Serotonin Inhibits Neuronal Excitability by Activating Two-pore Domain K⁺ channels in the Entorhinal Cortex. Molecular Pharmacology 72:208-218, 2007
8. Deng PY, LEI S. Long-term depression in identified stellate neurons of juvenile rat entorhinal cortex. Journal of Neurophysiology 97:727-737, 2007
9. Deng PY, Porter JE, Shin HS, LEI S. Thyrotropin-releasing hormone increases GABA release in rat hippocampus. Journal of Physiology 577:497-511, 2006
10. Deng PY, LEI S. Bidirectional Modulation of GABAergic Transmission By Cholecystokinin In Hippocampal Dentate Gyrus Granule Cells of Juvenile Rats. Journal of Physiology 572:425-442, 2006
11. LEI S, McBain CJ. Two loci of expression for long-term depression at hippocampal mossy fiber-interneuron synapses. Journal of Neuroscience 24:2112-2121, 2004
12. LEI, S., Topolnik, L, Congar, P, Lacaille, J-C. and McBain, C. J. Depolarization-induced Long-term Depression at Hippocampal Mossy Fiber CA3 Pyramidal Neuron Synapses. Journal of Neuroscience 23(30):9786-9795, 2003
13. LEI, S. and McBain, C. J. GABAB Receptor modulation of Excitatory and Inhibitory Synaptic Transmission onto rat CA3 Hippocampal Interneurons. Journal of Physiology 546:439-453, 2003
14. Arundine M, Chopra GK, Wrong A, LEI S, Aarts MM, MacDonald JF, Tymianski M.
    Enhanced Vulnerability to NMDA Toxicity in Sublethal Traumatic Neuronal
    Injury In-Vitro. Journal of Neurotrauma 20:1377-1395, 2003
15. LEI, S. and McBain, C. J. Distinct NMDA receptors provide differential modes of transmission at mossy fiber-interneuron synapses. Neuron 33:921-933, 2002
16. LEI, S., Czerwinska, E., Czerwinski, W., Walsh, M. P. and MacDonald, J. F. Regulation of NMDA receptor activity by F-actin and myosin-light chain kinase. Journal of Neuroscience 21:8464-8472, 2001
17. Atzori, M., LEI, S., Evans, D. I. P., Kanold, P. O., Phillips-Tansey, E., McIntyre, O. and McBain, C. J. Differential synaptic processing separates stationary from transient inputs to the auditory cortex. Nature Neuroscience 4:1230-1237, 2001
18. LEI, S., Dryden, W. F. and Smith, P. A. Nerve growth factor regulates sodium but not potassium channel currents in sympathetic B-neurons of adult bullfrogs. Journal of Neurophysiology 86: 641-650, 2001
19. LEI, S., MacDonald, J. F. Gadolinium reduces AMPA receptor desensitization and deactivation in hippocampal neurons. Journal of Neurophysiology 86: 173-182, 2001
20. LEI, S., B. A. Orser, G. R. L. Thatcher, J. N. Reynolds, and J. F. MacDonald. Positive allosteric modulators of AMPA receptors reduce proton-Induced receptor desensitization in rat hippocampal neurons. Journal of Neurophysiology 85: 2030-2038, 2001
21. LEI, S, Jackson MF, Jia Z, Roder J, Bai D, Orser BA, MacDonald JF. Cyclic GMP-dependent feedback inhibition of AMPA receptors is independent of PKG. Nature Neuroscience 3 : 559-565, 2000
22. LEI, S, Lu WY, Xiong ZG, Orser BA, Valenzuela CF, MacDonald JF. Platelet-derived Growth Factor Receptor-induced Feed-forward Inhibition of Excitatory Transmission between Hippocampal Pyramidal Neurons. Journal of Biological Chemistry 274 : 30617-30623, 1999
23. Lu W-Y, Xiong Z-G, LEI S., Orser B.A., Dudek E., Browning M, D., MacDonald J. F. G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nature Neuroscience 2: 331-338, 1999
24. LEI, S., Dryden, W. F. and Smith, P. A. Involvement of Ras/MAP kinase in the regulation of Ca²⁺ channels in adult bullfrog sympathetic neurons by nerve growth factor. Journal of Neurophysiology 80: 1352-1361, 1998
25. LEI, S., Dryden, W. F. and Smith, P. A. Regulation of N- and L-type Ca²⁺-channels in adult frog sympathetic ganglion B-cells by nerve growth factor in vitro and in vivo. Journal of Neurophysiology 78:3359-3370, 1997