Molecular mechanisms that stabilize short term synaptic plasticity during presynaptic homeostatic plasticity

  1. Jennifer M Ortega
  2. Özgür Genç
  3. Graeme W Davis  Is a corresponding author
  1. University of California, San Francisco, United States

Abstract

Presynaptic homeostatic plasticity (PHP) compensates for impaired postsynaptic neurotransmitter receptor function through a rapid, persistent adjustment of neurotransmitter release, an effect that can exceed 200%. An unexplained property of PHP is the preservation of short-term plasticity (STP), thereby stabilizing activity-dependent synaptic information transfer. We demonstrate that the dramatic potentiation of presynaptic release during PHP is achieved while simultaneously maintaining a constant ratio of primed to super-primed synaptic vesicles, thereby preserving STP. Mechanistically, genetic, biochemical and electrophysiological evidence argue that a constant ratio of primed to super-primed synaptic vesicles is achieved by the concerted action of three proteins: Unc18, Syntaxin1A and RIM. Our data support a model based on the regulated availability of Unc18 at the presynaptic active zone, a process that is restrained by Syntaxin1A and facilitated by RIM. As such, regulated vesicle priming/super-priming enables PHP to stabilize both synaptic gain and the activity-dependent transfer of information at a synapse.

Data availability

Data generate during this study are included in the manuscript and supporting files and tables.

Article and author information

Author details

  1. Jennifer M Ortega

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  2. Özgür Genç

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  3. Graeme W Davis

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    For correspondence
    graeme.davis@ucsf.edu
    Competing interests
    Graeme W Davis, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1355-8401

Funding

National Institute of Neurological Disorders and Stroke (R35NS097212)

  • Graeme W Davis

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

Reviewing Editor

  1. Yukiko Goda, RIKEN, Japan

Version history

  1. Received: July 24, 2018
  2. Accepted: November 12, 2018
  3. Accepted Manuscript published: November 13, 2018 (version 1)
  4. Version of Record published: November 22, 2018 (version 2)

Copyright

© 2018, Ortega 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. Jennifer M Ortega
  2. Özgür Genç
  3. Graeme W Davis
(2018)
Molecular mechanisms that stabilize short term synaptic plasticity during presynaptic homeostatic plasticity
eLife 7:e40385.
https://doi.org/10.7554/eLife.40385

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https://doi.org/10.7554/eLife.40385

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