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 in the last year is listed in the following. First, we found a GTP- and dynamin-independent form of endcoytosis at a central synapse (Nature Neuroscience, 2008). GTP- and dynamin were previously thought to underlie every form of endocytosis at synapses. Our study indicates taht this concept is incorrect and mechanisms other than the classical dynamin-mediated endocytosis can retrieve vesicles. Second, I have organized and chaired a symposium held in the Society of Neuroscience annual meeting (Oct, 2007) regarding the debate on the modes of fusion at synapses. In the most recent several years, the debate on how vesicles fuse at the plasma membrane to release transmtter had become very intense as several top labs, including mine, published results debating on whether there are kiss-and-run mode of fusion at synapses. Kiss-and-run mode may generate less postsynaptic current than the classical full collapse mode of fusion, and thus provide a mechanism to regulate the synaptic strength, the mechanism that may underlie learninig and memory, and synapse development. We have published two articals that proivde the current status for this debate (Trends in Neuroscience, 2007; J Neurosci, 2007). In addition, the symposium that I chaired has increased the interest of public on the study of synaptic transmission. Based on this symposium, an articel was published in Scientific American Mind (December, 2007/January, 2008 issue, Page 12-13) describing how interesting, how important, and how hard to even resolve the mode of fusion at synapses, which may broden the public interst in our research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS003009-05
Application #
7735298
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2008
Total Cost
$2,428,977
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