1. Neuroscience
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Incomplete vesicular docking limits synaptic strength under high release probability conditions

  1. Gerardo Malagon
  2. Takafumi Miki
  3. Van Tran
  4. Laura Gomez
  5. Alain Marty  Is a corresponding author
  1. Washington University, United States
  2. Doshisha University, Japan
  3. Paris Descartes University, France
  4. Université de Paris, France
Research Article
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Cite this article as: eLife 2020;9:e52137 doi: 10.7554/eLife.52137

Abstract

Central mammalian synapses release synaptic vesicles in dedicated structures called docking/release sites. It has been assumed that when voltage-dependent calcium entry is sufficiently large, synaptic output attains a maximum value of one synaptic vesicle per action potential and per site. Here we use deconvolution to count synaptic vesicle output at single sites (mean site number per synapse: 3.6). When increasing calcium entry with tetraethylammonium in 1.5 mM external calcium concentration, we find that synaptic output saturates at 0.22 vesicle per site, not at 1 vesicle per site. Fitting the results with current models of calcium-dependent exocytosis indicates that the 0.22 vesicle limit reflects the probability of docking sites to be occupied by synaptic vesicles at rest, as only docked vesicles can be released. With 3 mM external calcium, the maximum output per site increases to 0.47, indicating an increase in docking site occupancy as a function of external calcium concentration.

Data availability

Igor files of the analysis, that contain the entire list of analysis operations are provided as Source Data 1.

Article and author information

Author details

  1. Gerardo Malagon

    Department of Cell Biology and Physiology, Washington University, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Takafumi Miki

    Graduate School of Brain Science, Doshisha University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Van Tran

    SSPIN-Saints Peres Institue for the Neurosciences, Paris Descartes University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Laura Gomez

    SSPIN-Saints Peres Institue for the Neurosciences, Paris Descartes University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Alain Marty

    SPPIN-Saints Pères Paris Institute for the Neurosciences, Université de Paris, Paris, France
    For correspondence
    alain.marty@parisdescartes.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6478-6880

Funding

H2020 European Research Council (294509)

  • Gerardo Malagon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany

Publication history

  1. Received: September 23, 2019
  2. Accepted: March 23, 2020
  3. Accepted Manuscript published: March 31, 2020 (version 1)
  4. Version of Record published: April 6, 2020 (version 2)

Copyright

© 2020, Malagon et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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