Vitaly A. Klyachko, Ph.D.
Cell Biology and Physiology
Synapses are believed to represent the computational units of the brain and synaptic plasticity is believed to underlie many essential brain functions including information processing. Yet, due to inaccessibility of most central synapses to conventional experimental techniques, many basic synaptic mechanisms and their computational significance remain elusive. Research in my laboratory is focused on understanding the mechanisms and regulation of neurotransmitter release in central synapses in healthy and disease conditions. Our second major interest is elucidating the functional roles of presynaptic processes in synaptic plasticity and information processing. We are currently developing three main projects to address these questions by:
1. Studying presynaptic release mechanisms and synaptic vesicle cycling at the level of individual synapses. Using super-resolution imaging techniques in combination with advanced image analysis and computational approaches we can simultaneously visualize movements and release of several vesicles inside a synapse. In parallel, we use high-resolution capacitance measurements to detect and study fusion of individual synaptic vesicles at active zones.
2. Investigating how presynaptic processes give rise to short-term plasticity and how this plasticity determines information processing by individual synapses and functional circuits. Using natural spike trains recorded in behaving rodents we extend this analysis from individual synapses to the circuit level, and investigate synaptic interactions in basic feed-forward and feed-back circuits.
3. Relating deregulation in synaptic mechanisms with the impairment of information processing observed in many developmental diseases, such as Fragile X syndrome. We use mouse model of Fragile X syndrome and a variety of imaging, electrophysiological, biochemical and behavioral approaches to analyze how synaptic function and plasticity in cortical and hippocampal neurons is affected in this disorder.
Deng P.Y, Rotman Z, Blundon J.A., Cho Y, Cui J., Cavalli V., Zakharenko S.S., Klyachko V.A. FMRP regulates neurotransmitter release and synaptic information transmission by controlling action potential duration via BK channels. Neuron, 77:696-711. 2013. Featured article.
Peng A., Rotman Z., Deng P.Y. and Klyachko V.A. Differential motion dynamics of synaptic vesicles undergoing spontaneous and activity-evoked endocytosis. Neuron, 73:1108-15. 2012. Featured Article, Selected by Faculty of 1000.
Rotman Z. Deng P.Y. and Klyachko V.A. Short-term plasticity optimizes synaptic information transmission. J. Neurosci, 31:14800-9. 2011. Featured in This Week in Journal.
Deng P.Y., Sojka D., Klyachko V.A. Abnormal presynaptic short-term plasticity and information processing in a mouse model of Fragile X Syndrome. J. Neurosci, 31:10971-82. 2011.
Kandaswamy U, Deng P.Y., Stevens C.F. Klyachko V.A. The role of presynaptic dynamics in processing of natural spike trains in hippocampal synapses. J. Neurosci, 30:15904-14. 2010.
Klyachko V. A. and Stevens C. F. (2006) Excitatory and feed-forward inhibitory hippocampal synapses work synergistically as an adaptive filter of natural spike trains PLoS Biology, 4:e207.
Klyachko VA and Jackson MB. Capacitance steps and fusion pores of small and large-dense-core vesicles in nerve terminals. Nature 2002 418: 89-92.
Last Updated: 8/1/2013 4:08:21 PM