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Cited by 51Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

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Leitz, Jeremy, Kavalali, Ege T·2014·eLife
DOI 10.7554/elife.03658PMC PMC4270043
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Abstract

Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion.

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Cited by

Sorted by citations

Authors
Leitz, J., & Kavalali, E. T.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Kavalali, Ege T
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2014-11-21
Volume
3
Pages
e03658-e03658
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.03658
PMC
PMC4270043
OpenAlex
W2153309256
Cited by
51
References
4
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 9 · 2015: 6
FWCI
3.49
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Mental Health (R01 MH066198)
  • National Institute of Neurological Disorders and Stroke (NINDS) (T32 NS069562)
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
spontaneous neurotransmitter release, synaptic vesicle recycling, calcium-dependent regulation, NMDA receptor, presynaptic terminals, pH-sensitive fluorescent probe, quantal analysis, endocytosis, exocytosis
MeSH terms
Animals, Endocytosis, Extracellular Space, Female, Fluorescence, Humans, Kinetics, Male, Membrane Fusion, Synapses, Synaptic Vesicles, Time Factors, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Calcium Signaling, Green Fluorescent Proteins, Vesicular Glutamate Transport Protein 1, HEK293 Cells

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