In the brain, synapses are the principal sites for interneuronal communication. Synaptic communication is initiated by the fusion of synaptic vesicles with the presynaptic plasma membrane giving rise to the release of neurotransmitters into the synaptic cleft and activation of postsynaptic receptors. Short or long-term activity-dependent modifications in synapses underlie the information processing and storage capacity of the central nervous system. As a consequence, alterations in basic synaptic structure and function are responsible for numerous neurological and neuropsychiatric disorders.
Our research focuses on the basic mechanisms that underlie the formation and function of synapses in the central nervous system. Over the past few years our group has worked on several facets of synaptic transmission between central neurons. Our studies encompass four areas. First, we investigated the function of synaptobrevin, a major vesicle associated SNARE protein critical for fusion, and uncovered its role in coupling synaptic vesicle exocytosis and retrieval. Second, we demonstrated that neurotransmission is not sustained by release of vesicles from an infinite reservoir but by constant rapid reuse of a handful of vesicles. We could also show that this rapid synaptic vesicle reuse is a highly plastic and dynamically regulated process that potently impacts synaptic transmission within seconds or possibly milliseconds during repetitive activity. Third, we spent significant effort to elucidate the molecular basis of synaptogenesis. In this project, we showed that expression of synaptic cell adhesion molecules, SynCAM and neuroligin, in non-neuronal as well as neuronal cells was sufficient for full functional assembly of presynaptic terminals within incoming axons. Lastly, our recent studies have contributed to the hypothesis that spontaneous neurotransmission is a bona fide pathway for interneuronal signaling which may operate independent of evoked transmission via distinct presynaptic as well as postsynaptic substrates.
RESEARCH INTERESTS
Synaptic Transmission
Electrophysiology
Short-term synaptic plasticity
RECENT PUBLICATIONS
Chubykin AA, Atasoy D, Etherton MR, Brose N, Kavalali ET, Gibson JR, Sudhof TC, "Activity-dependent validation of excitatory versus inhibitory synapses by Neuroligin-1 versus Neuroligin-2" Neuron, 54:919-931, 2007
Ertunc M, Sara Y, Chung C, Atasoy D, Virmani T, Kavalali ET, "Fast synaptic vesicle reuse slows the rate of synaptic depression in the CA1 region of hippocampus" The Journal of Neuroscience, 27:341-354, 2007
Wasser C, Ertunc M, Liu X, Kavalali ET, "Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling" The Journal of Physiology (Lond.), 579:413-429, 2007
Nelson ED, Kavalali ET, Monteggia LM, "MeCP2-dependent transcriptional repression regulates excitatory neurotransmission" Current Biology, 16:710-716, 2006
Virmani T, Atasoy D, Kavalali ET, "Synaptic vesicle recycling adapts to chronic changes in activity" The Journal of Neuroscience, 26:2197-2206, 2006
SIGNIFICANT PUBLICATIONS
Sara Y, Virmani T, Deak F, Liu X, Kavalali ET, "An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission" Neuron, 45:563-573, 2005
Sara Y, Biederer T, Atasoy D, Chubykin A, Mozhayeva MG, Sudhof TC, Kavalali ET, "Selective capability of SynCAM and Neuroligin for functional synapse assembly" The Journal of Neuroscience, 25:260-270, 2005
Deak F, Schoch S, Liu X, Sudhof TC, Kavalali ET, "Synaptobrevin is essential for fast synaptic vesicle endocytosis" Nature Cell Biology, 6:1102-1108, 2004
Mozhayeva MG, Sara Y, Liu X, Kavalali ET, "Development of vesicle pools during maturation of hippocampal synapses" The Journal of Neuroscience, 22:654-665, 2002
Schoch S, Deak F, Konigstorfer A, Mozhayeva M, Sara Y, Sudhof TC, Kavalali ET, "SNARE function analyzed in synaptobrevin/VAMP knockout mice" Science, 294:1117-1122, 2001
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