1. Neurosciences Program, University of California, San Diego, La Jolla, California 92093, USA
2. Howard Hughes Medical Institute, and Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA

Correspondence to: Charles F. Stevens² Correspondence and requests for materials should be addressed to C.F.S. (Email: cfs@salk.edu).

Abstract

Synapses recycle their spent vesicles in order to keep up with on-going neurotransmitter release. To investigate vesicle recycling in the small synapses of hippocampal neurons, we have used an optical recording method that permits us to resolve single-vesicle events. Here we show that an exocytic event can terminate with three modes of vesicle retrieval: a fast (400–860 ms) 'kiss-and-run' mode that has a selective fusion pore; a slow (8–21 s) 'compensatory' mode; and a 'stranded' mode of recycling, in which a vesicle is left on the cell surface until a nerve impulse triggers its retrieval. We have also observed that, in response to a nerve impulse, synapses with low release probability primarily use the kiss-and-run mode, whereas high release probability terminals predominantly use the compensatory mode of vesicle retrieval.