Neurons contact each other mostly by synaptic transmission at synapses. Synaptic transmission relies on vesicle exocytosis, i.e., fusion of vesicles with the plasma membrane and release of transmission. To maintain vesicle exocytosis, fused vesicles must be retrieved, or endocytosed, to form new vesicles for the second round of exocytosis. My goal is to improve our understanding on the cellular and molecular mechanisms underlying synaptic vesicle exocytosis and endocytosis, which are the building block for synaptic transmission and thus the signaling process in the neuronal network. My progress from Oct. 1, 2003 to now is listed in the following. First, we have developed a new method to study exocytosis at a calyx-type synapse in the mammalian central nervous system. This ended up a publication in Journal of Neuroscience Method, 2004. Secondly, we found that a clinically used volatile anesthetic, isoflurane, inhibits synaptic transmission by reducing the presynaptic action potential waveform. This finding may advance our understanding on how volatile anesthetics work to achieve its anesthetic action. The finding has been published in Journal of Anesthesiology, 2004. Third, I have provided an undated review on the study of the kinetic of endocytosis, which is critical for nerve terminals to maintain synaptic transmission. The review was published in Trends in Neuroscience, 2004. Fourthly, we have studied the molecular mechanisms underlying synaptic plasticity, particularly short-term synaptic depression. We found a novel mechanism that may underlie short-term synaptic depression. The work is in preparation of submission. Finally, we are in the progress of developing a method to study the molecular mechanisms of endocytosis. The method may shed light on the molecular mechanisms underlying modulation of the kinetics of endocytosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS003009-01
Application #
6990794
Study Section
(STU)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2004
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
He, Liming; Wu, Ling-Gang (2007) The debate on the kiss-and-run fusion at synapses. Trends Neurosci 30:447-55
Wu, Ling-Gang; Ryan, Timothy A; Lagnado, Leon (2007) Modes of vesicle retrieval at ribbon synapses, calyx-type synapses, and small central synapses. J Neurosci 27:11793-802
He, Liming; Wu, Xin-Sheng; Mohan, Raja et al. (2006) Two modes of fusion pore opening revealed by cell-attached recordings at a synapse. Nature 444:102-5
Xu, Jianhua; Wu, Ling-Gang (2005) The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse. Neuron 46:633-45
Wu, Wei; Xu, Jianhua; Wu, Xin-Sheng et al. (2005) Activity-dependent acceleration of endocytosis at a central synapse. J Neurosci 25:11676-83