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Cited by 138Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Synaptic vesicles transiently dock to refill release sites

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Kusick, Grant F., Chin, Morven, Raychaudhuri, Sumana, Lippmann, Kristina, Adula, Kadidia P., Hujber, Edward J., Vu, Thien, Davis, M. Wayne +2 more·2020·Nature Neuroscience
DOI 10.1038/s41593-020-00716-1PMC PMC8054220

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Abstract

Synaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must 'dock' to refill vacated release sites. 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. Fusions during synchronous release are distributed throughout the active zone, whereas fusions during asynchronous release are biased toward the center of the active zone. After stimulation, the total number of docked vesicles across all synapses decreases by ~40%. Within 14 ms, new vesicles are recruited and fully replenish the docked pool, but this docking is transient and they either undock or fuse within 100 ms. These results demonstrate that the recruitment of synaptic vesicles to release sites is rapid and reversible.

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  • At ~1 mM calcium, 62% of responding synapses have only one vesicle fusion immediately after stimulation.

    “At this calcium concentration, 62% of responding synapses have only one vesicle fusion immediately after stimulation39.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [39]

  • With physiological extracellular calcium (~1 mM), only 1-2 vesicles fuse on average in synapses that respond to a single action potential.

    “However, with a physiological extracellular calcium concentration ( ~1 mM)64, only 1–2 vesicles fuse on average in synapses that respond to a single action potential39,62.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [39]

  • Fusion of an additional vesicle leads to the formation of membrane pits if the second vesicle fuses before the first completely flattens out, about 10 ms after an action potential.

    “This simulation suggests that fusion of an additional vesicle leads to the formation of membrane pits if the second vesicle fuses before the first completely flattens out ( ~10 ms after an action potential39) (Fig. 3i, j).”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [39]

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Authors
Kusick, G. F., Chin, M., Raychaudhuri, S., Lippmann, K., Adula, K. P., Hujber, E. J., Vu, T., Davis, M. W., Jorgensen, E. M., & Watanabe, S.
Affiliations
  • Johns Hopkins University (US)
  • Harvard University (US)
  • Marine Biological Laboratory (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Watanabe, Shigeki
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2020-09-28
Volume
23
Issue
11
Pages
1329-1338
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-020-00716-1
PMC
PMC8054220
OpenAlex
W3089847221
Cited by
138
References
13
Citations by year
2026: 12 · 2025: 23 · 2024: 22 · 2023: 29 · 2022: 23 · 2021: 18 · 2020: 8 · 2019: 3
FWCI
9.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (2016217537)
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (T32 GM007445)
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R25NS063307, 1R01 NS105810-01A1, 1DP2 NS111133-01)
  • Howard Hughes Medical Institute
  • NSF | ENG/OAD | Division of Civil, Mechanical and Manufacturing Innovation (1727260)
  • McKnight Endowment Fund for Neuroscience
  • Alfred P. Sloan Foundation
  • Esther A. and Joseph Klingenstein Fund
  • Johns Hopkins University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
synaptic vesicle docking, synaptic vesicle recycling, neurotransmitter release, active zone, vesicle fusion, synchronous release, asynchronous release, high-pressure freezing, time-resolved electron microscopy, hippocampal synapses, short-term plasticity, vesicle replenishment
MeSH terms
Animals, Cells, Cultured, Exocytosis, Female, Hippocampus, Male, Mice, Inbred C57BL, Neurons, Synaptic Vesicles

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