Synaptic Vesicle Cycle at Nerve Terminals

Synaptic vesicle fusion at the plasma membrane is followed by vesicle retrieval. There are three different pathways for retrieving vesicles: classic clathrin-mediated endocytosis, a “kiss-and-run” form of endocytosis, and bulk endocytosis. These forms of endocytosis may take as long as tens to hundreds of seconds or as short as one second or less. The time course of endocytosis is determined by the neuronal firing frequency and duration. The dynamic time course could be a result of multiple endocytic pathways and/or regulation by a variety of modulators. The newly formed vesicles via various endocytic pathways may join the readily releasable pool or the reserve pool, likely depending on which pathway they are generated. Vesicles in the reserve pool can be mobilized to the readily releasable pool, when the latter is depleted. Vesicle recycling is critical for the maintenance of transmitter release during repetitive stimulation. Regulation of any step in the vesicle cycling process, including endocytosis, could thus provide a mechanism by which synaptic plasticity is achieved.