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Cited by 447Cellular transport and secretionNeuroscience and Neuropharmacology ResearchCalcium signaling and nucleotide metabolism

Molecular Mechanisms for Synchronous, Asynchronous, and Spontaneous Neurotransmitter Release

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Kaeser, Pascal S., Regehr, Wade G.·2014·Annual Review of Physiology
DOI 10.1146/annurev-physiol-021113-170338PMC PMC4503208
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Abstract

Most neuronal communication relies upon the synchronous release of neurotransmitters, which occurs through synaptic vesicle exocytosis triggered by action potential invasion of a presynaptic bouton. However, neurotransmitters are also released asynchronously with a longer, variable delay following an action potential or spontaneously in the absence of action potentials. A compelling body of research has identified roles and mechanisms for synchronous release, but asynchronous release and spontaneous release are less well understood. In this review, we analyze how the mechanisms of the three release modes overlap and what molecular pathways underlie asynchronous and spontaneous release. We conclude that the modes of release have key fusion processes in common but may differ in the source of and necessity for Ca(2+) to trigger release and in the identity of the Ca(2+) sensor for release.

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Crossref · 10.1146/annurev-physiol-021113-170338

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  • Exocytosis occurs in three modes: synchronous, asynchronous, and spontaneous, which share core fusion machinery but differ in calcium sensor requirements.

    “This exocytosis occurs in three modes: synchronous (triggered by action potentials), asynchronous (with variable delay), and spontaneous (in the absence of stimuli), which share core fusion machinery but differ in calcium sensor requirements [25].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [25]

    The Abstract describes the three release modes, their shared key fusion processes, and possible differences in Ca2+ sensors. But the claim makes those sensor differences categorical: the Spontaneous Release section says spontaneous release may use the same fast synaptotagmin sensor as synchronous release or a specialized sensor. The paper also specifies absence of action potentials, rather than absence of all stimuli. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Synaptic vesicles can fuse synchronously within a few milliseconds of an action potential and asynchronously thereafter over tens and hundreds of milliseconds.

    “Synaptic vesicles can fuse synchronously within a few milliseconds of an action potential and asynchronously thereafter over tens and hundreds of miliseconds65.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [65]

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References 221 · Cited by 447

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Authors
Kaeser, P. S., & Regehr, W. G.
Affiliations
Harvard University (US)
ORCID
Venue
Annual Review of Physiology
Publisher
Annual Reviews
Published
2014-02-10
Volume
76
Issue
1
Pages
333-363
ISSN
  • 0066-4278 (ISSN-L)
  • 1545-1585
DOI
10.1146/annurev-physiol-021113-170338
PMC
PMC4503208
OpenAlex
W2132653427
Cited by
447
References
221
Citations by year
2026: 28 · 2025: 27 · 2024: 43 · 2023: 37 · 2022: 39 · 2021: 37 · 2020: 40 · 2019: 45 · 2018: 35 · 2017: 33 · 2016: 28 · 2015: 31 · 2014: 23
FWCI
3.15
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Drug Abuse (K01DA029044)
  • National Institute of Neurological Disorders and Stroke (R01-NS32405, R01NS032405)
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 › Physiology › Calcium signaling and nucleotide metabolism
Keywords
neurotransmitter release, asynchronous release, spontaneous release, synchronous release, synaptic vesicle exocytosis, action potential, presynaptic terminals, calcium-triggered release, calcium sensor, vesicle fusion, synaptic transmission
MeSH terms
Animals, Calcium, Exocytosis, Humans, Synaptic Transmission, Synaptic Vesicles, Receptors, Presynaptic, Neurotransmitter Agents, SNARE Proteins

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