Gong Chen
Associate Professor of BiologyOffice: 224 Life Sciences
Phone: 865-2488
Lab Address: 226 Life Sciences
Lab Phone: 863-2992
Contact: Gong Chen
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Education
- Ph. D., Shanghai Institute of Physiology, Chinese Academy of Sciences, 1993
Postdoc Training
- Stanford University
- Yale University
Honors and Awards
- National Research Service Award from NIH at Stanford University 1999-2001
- Ohse Award at Yale University 1995
Research Interests
Molecular mechanisms of synaptogenesis and plasticity
Our research is focusing on fundamental mechanisms of synaptogenesis and synaptic plasticity. Synapses are elementary units of neuronal connections. How an axon of one neuron contacts the dendrite or soma of another neuron to form a synapse is a fundamental question during brain development, learning and memory, and brain repair. Once a synapse is established, the synaptic strength can be dynamically changed, which is called synaptic plasticity. The cellular basis of learning and memory is believed to be encoded in the changes of synaptic strength of thousands or even millions of synapses.
We study the molecular and cellular mechanisms of synaptogenesis and plasticity using multidiscipline approaches, including molecular biology, electrophysiology, fluorescence imaging, cell culture, immunocytochemistry, and electronmicroscopy. We also established a single-synapse-recording system to study synaptic transmission at visualized single synapses. It provides us novel opportunities to monitor the functional assembly of single synapses at microscopic level.
We have successfully reconstructed GABAergic synapses in non-neuronal cells using a molecular engineering method (Dong et al., 2007). We also demonstrated that immature synapses are presynaptically silent, and activation of presynaptic silent synapses requires repetitive neuronal activity and actin polymerization (Yao et al., 2006). We developed an improved Ca2+-phosphate transfection protocol which greatly increased the transfection efficiency and can be applied to both immature and mature neurons (Jiang and Chen, 2006). We also established a novel epilepsy model induced by cyclothiazide (Qi et al., 2006a, 2006b).
Neural stem cell research
We are applying the knowledge learned from studying synapse formation and synaptic plasticity to neural stem cell research. Our goal is to find out ways to facilitate stem cell differentiation and functional integration into adult neural networks. Rapid formation of synapses between new born neurons and existing mature neurons in the adult brain is a key issue for a successful stem cell therapy to treat neurodegenerative disorders. Our main focus is to use stem cell therapy to treat Alzheimers disease.
Selected Publications
Deng, L., Yao, J., Fang, C., Dong, N., Luscher, B., and Chen, G. (2007). Sequential postsynaptic maturation governs the temporal order of GABAergic and glutamatergic synaptogenesis in rat embryonic cultures. Journal of Neuroscience, 27(40):10860-10869.
Dong, N., Qi, J., Chen, G. (2007). Molecular reconstitution of functional GABAergic synapses with expression of neuroligin-2 and GABAA receptors. Mol. Cell. Neurosci. 35: 14 - 23.
Wendou Yu, Min Jiang, Celia P. Miralles, Gong Chen and Angel L. de Blas. (2007). Gephyrin clustering is required for the stability of GABAergic synapses. Mol. Cell. Neurosci. 36(4):484-500.
Fang, C., Deng, L., Keller, C., Fukata, M., Fukata, Y., Chen, G., and Lüscher, B. (2006). GODZ-mediated palmitoylation of GABAA receptors is required for normal assembly and function of GABAergic inhibitory synapses. Journal of Neuroscience 26(49): 12758-12768 .
Qi, J. S., Yao, J., Fang, C., Lüscher, B., and Chen, G. (2006). Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal cultures. Journal of Physiology 577(2): 579-590.
Yao, J., Qi, J. S., and Chen, G. (2006). Actin-dependent activation of presynaptic silent synapses contributes to long-term synaptic plasticity in developing hippocampal neurons. Journal of Neuroscience, 26 (31): 8137 - 8147.
Jiang, M. and Chen, G. (2006). High Ca2+-phosphate transfection efficiency in low-density neuronal cultures. Nature Protocols, Vol. 1. (No. 2) 695 - 700. (Invited article)
Qi, J.S., Wang, Y., Jiang M., Warren, W., and Chen, G. (2006). Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo. Journal of Physiology 571(3): 605-618.
Zhou, J., Pfaff, D. W., and Chen, G. (2005). Sex differences in estrogenic regulation of neuronal activity in neonatal cultures of ventromedial nucleus of the hypothalamus. PNAS 102: 14907-14912.
Alldred, M.J., Mulder-Rosi, J., Lingenfelter, S. E., Chen, G., and Lüscher, B. (2005) Distinct 2 Subunit Domains Mediate Clustering and Synaptic Function of Postsynaptic GABAA Receptors and Gephyrin. Journal of Neuroscience 25(3): 594-603.
Jiang, M., Deng, L.B., and Chen, G. (2004). High Ca2+-phosphate transfection efficiency enables single neuron gene analysis. Gene Therapy 11:1303-1311.
Cao, Y-Q., Piedras-Renteria, E., Smith, G. B., Chen, G., Harata, N. C., Tsien, R. W. (2004). Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy. Neuron 43: 387-400.
Chen, G., Harata, N. and Tsien, R. W. (2004). Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses. PNAS 101: 1063-1068.
Deng, L. B., and Chen, G. (2003). Cyclothiazide potently inhibits -aminobutyric acid type A receptors in addition to enhancing glutamate responses. PNAS 100 (22): 13025-13029.
Chen, Y., Deng, L. B., Maeno-Hikichi, Y., Lai, M. Z., Chang, S. H., Chen, G., and Zhang, J. F. (2003). Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis. Cell 115: 37-48.
Chen, G., and van den Pol, A. N. (1998). Presynaptic GABA-B autoreceptor modulation of P/Q-type calcium channels and GABA release in rat suprachiasmatic nucleus neurons. Journal of Neuroscience 18:1913-1922.
Chen, G., and van den Pol, A. N. (1998). Coexpression of multiple metabotropic glutamate receptors in axon terminals of single suprachiasmatic nucleus neurons. Journal of Neurophysiology 80:1932-1938.
Gao, X. B., Chen, G., and van den Pol, A. N. (1998). GABA-dependent firing of glutamate-evoked action potentials at AMPA/kainate receptors in developing hypothalamic neurons. Journal of Neurophysiology 79: 716-726.
Chen, G., and van den Pol, A. N. (1997). Adenosine modulation of calcium currents and presynaptic inhibition of GABA release in suprachiasmatic and arcuate nucleus neurons. Journal of Neurophysiology 77: 3035-3047.
Chen, G., and van den Pol, A. N. (1996). Multiple NPY receptors coexist in pre- and postsynaptic sites: inhibition of GABA release in isolated self-innervating SCN neurons. Journal of Neuroscience 16: 7711-7724.
Chen, G., Trombley, P. Q., and van den Pol, A. N. (1996). Excitatory actions of GABA in developing hypothalamic neurons. Journal of Physiology 494: 451-464.
van den Pol, A. N, Obrietan, K., and Chen, G. (1996). Excitatory actions of GABA after neuronal trauma. Journal of Neuroscience 16: 4283-4292.
van den Pol, A. N., Obrietan, K., Chen, G., and Belousov, A. (1996). Neuropeptide Y-mediated long-term depression of excitatory activity in suprachiasmatic nucleus neurons. Journal of Neuroscience 16: 5883-5895.
Chen, G., Trombley, P. Q., and van den Pol, A. N. (1995). GABA receptors precede glutamate receptors in hypothalamic development; differential regulation by astrocytes. Journal of Neurophysiology 74: 1473-1484.