Synaptic vesicles undock and then transiently dock after an action potential

Grant F. Kusick, Morven Chin, Kristina Lippmann, Kadidia P. Adula, M. Wayne Davis, Erik M. Jorgensen, Shigeki Watanabe

Research output: Contribution to journalArticlepeer-review


Synaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must refill vacated release sites. How many vesicles can fuse at a single active zone, where they fuse within the active zone, and how quickly they are replaced with new vesicles is not well-established. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone; this multivesicular release is augmented by increasing the extracellular calcium concentration. Synchronous fusions are distributed throughout the active zone, whereas asynchronous fusions are biased toward the center of the active zone. Immediately after stimulation a large fraction of vesicles become undocked. Between 8 and 14 ms, new vesicles are recruited to the plasma membrane and fully replenish the docked pool, but docking of these vesicles is transient and they either undock or fuse within 100 ms. These results demonstrate that recruitment of synaptic vesicles to release sites is rapid and reversible.

Original languageEnglish (US)
JournalUnknown Journal
StatePublished - Dec 31 2018


  • asynchronous release
  • flash-and-freeze
  • multivesicular release
  • neurotransmitter release
  • synaptic vesicle docking
  • Synaptic vesicle exocytosis
  • transient docking
  • zap-and-freeze

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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