| The maximal steady state rate of synaptic transmission is limited by how fast the synapse can replenish the small pool of vesicles available for release [1, 2]. One of the major rate-limiting steps in replenishment is the retrieval of used vesicles from the cell surface. Despite extensive study [3--17], the means of vesicle retrieval remains controversial because no technique has been available to measure single vesicle recycling in synapses.; Using an optical indicator for the exposure of the vesicle lumen to the external medium [18], I recorded the evoked recycling of single vesicles in cultured, hippocampal synapses. I show that, after exocytosis, a synaptic vesicle has three options for retrieval: a fast, "kiss-and-run" mode; a slower, "compensatory" mode; and a "stranded" mode in which retrieval is delayed until triggered by the arrival of a nerve impulse. In the kiss-and-run mode vesicles communicate to the external medium through a low permeability fusion pore. The mode of recycling employed by a synapse depends upon its release probability; low release probability terminals predominantly kiss-and-run recycle, whereas high release probability synapses primarily use compensatory recycling. |
