Physical determinants of vesicle mobility and supply at a central synapse

  1. Jason Seth Rothman
  2. Laszlo Kocsis
  3. Etienne Herzog
  4. Zoltan Nusser  Is a corresponding author
  5. Robin Angus Silver  Is a corresponding author
  1. University College London, United Kingdom
  2. Hungarian Academy of Sciences, Hungary
  3. Max Planck Institute of Experimental Medicine, Germany

Abstract

Encoding continuous sensory variables requires sustained synaptic signalling. At several sensory synapses, rapid vesicle supply is achieved via highly mobile vesicles and specialized ribbon structures, but how this is achieved at central synapses without ribbons is unclear. Here we examine vesicle mobility at excitatory cerebellar mossy fibre synapses which sustain transmission over a broad frequency bandwidth. Fluorescent recovery after photobleaching in slices from VGLUT1Venus knock-in mice reveal 75% of VGLUT1-containing vesicles have a high mobility, comparable to that at ribbon synapses. Experimentally constrained models establish hydrodynamic interactions and vesicle collisions are major determinants of vesicle mobility in crowded presynaptic terminals. Moreover, models incorporating 3D reconstructions of vesicle clouds near active zones (AZs) predict the measured releasable pool size and replenishment rate from the reserve pool. They also show that while vesicle reloading at AZs is not diffusion-limited at the onset of release, diffusion limits vesicle reloading during sustained high-frequency signalling.

Article and author information

Author details

  1. Jason Seth Rothman

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3036-2291
  2. Laszlo Kocsis

    Laboratory of Cellular Neurophysiology, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Etienne Herzog

    Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0058-6959
  4. Zoltan Nusser

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    For correspondence
    nusser@koki.hu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7004-4111
  5. Robin Angus Silver

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    For correspondence
    a.silver@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5480-6638

Funding

Wellcome Trust (95667)

  • Robin Angus Silver

European Research Council (294667)

  • Robin Angus Silver

European Research Council (293681)

  • Zoltan Nusser

Magyar Tudományos Akadémia (Momentum Grant, Lendület, LP2012-29)

  • Zoltan Nusser

European Commission (LSHM-CT-2005-019055)

  • Zoltan Nusser
  • Robin Angus Silver

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

Reviewing Editor

  1. Christian Rosenmund, Charité-Universitätsmedizin Berlin, Germany

Ethics

Animal experimentation: Animal experiments were conducted in strict accordance with the United Kingdom Home Office Animals Scientific Procedures Act of 1986, and approved by the UCL ethics review board. All mice were anaesthetized with ketamine or isoflurane during surgical procedures.

Version history

  1. Received: February 9, 2016
  2. Accepted: August 14, 2016
  3. Accepted Manuscript published: August 19, 2016 (version 1)
  4. Accepted Manuscript updated: August 23, 2016 (version 2)
  5. Version of Record published: September 15, 2016 (version 3)

Copyright

© 2016, Rothman 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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  1. Jason Seth Rothman
  2. Laszlo Kocsis
  3. Etienne Herzog
  4. Zoltan Nusser
  5. Robin Angus Silver
(2016)
Physical determinants of vesicle mobility and supply at a central synapse
eLife 5:e15133.
https://doi.org/10.7554/eLife.15133

Share this article

https://doi.org/10.7554/eLife.15133

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