1. Neuroscience
Download icon

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
  • Cited 7
  • Views 988
  • Annotations
Cite this article as: eLife 2020;9:e52137 doi: 10.7554/eLife.52137


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
    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


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)


© 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.


  • 988
    Page views
  • 234
  • 7

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Zhengchao Xu et al.
    Tools and Resources Updated

    The dorsal raphe nucleus (DR) and median raphe nucleus (MR) contain populations of glutamatergic and GABAergic neurons that regulate diverse behavioral functions. However, their whole-brain input-output circuits remain incompletely elucidated. We used viral tracing combined with fluorescence micro-optical sectioning tomography to generate a comprehensive whole-brain atlas of inputs and outputs of glutamatergic and GABAergic neurons in the DR and MR. We found that these neurons received inputs from similar upstream brain regions. The glutamatergic and GABAergic neurons in the same raphe nucleus had divergent projection patterns with differences in critical brain regions. Specifically, MR glutamatergic neurons projected to the lateral habenula through multiple pathways. Correlation and cluster analysis revealed that glutamatergic and GABAergic neurons in the same raphe nucleus received heterogeneous inputs and sent different collateral projections. This connectivity atlas further elucidates the anatomical architecture of the raphe nuclei, which could facilitate better understanding of their behavioral functions.

    1. Neuroscience
    Shankar Ramachandran et al.
    Research Article Updated

    Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits.