The synaptic vesicle cycle revisited: New insights into the modes and mechanisms

Natali L. Chanaday, Michael A. Cousin, Ira Milosevic, Shigeki Watanabe, Jennifer R. Morgan

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Neurotransmission is sustained by endocytosis and refilling of synaptic vesicles (SVs) locally within the presynapse. Until recently, a consensus formed that after exocytosis, SVs are recovered by either fusion pore closure (kiss-and-run) or clathrin-mediated endocytosis directly from the plasma membrane. However, recent data have revealed that SV formation is more complex than previously envisaged. For example, two additional recycling pathways have been discovered, ultrafast endocytosis and activity-dependent bulk endocytosis, in which SVs are regenerated from the internalized membrane and synaptic endosomes. Furthermore, these diverse modes of endocytosis appear to influence both the molecular composition and subsequent physiological role of individual SVs. In addition, previously unknown complexity in SV refilling and reclustering has been revealed. This review presents a modern view of the SV life cycle and discusses how neuronal subtype, physiological temperature, and individual activity patterns can recruit different endocytic modes to generate new SVs and sculpt subsequent presynaptic performance.

Original languageEnglish (US)
Pages (from-to)8209-8216
Number of pages8
JournalJournal of Neuroscience
Issue number42
StatePublished - 2019

ASJC Scopus subject areas

  • General Neuroscience


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