Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

  1. Michael A Gaviño
  2. Kevin J Ford
  3. Santiago Archila
  4. Graeme W Davis  Is a corresponding author
  1. University of California, San Francisco, United States

Abstract

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

Article and author information

Author details

  1. Michael A Gaviño

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  2. Kevin J Ford

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  3. Santiago Archila

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  4. 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.

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Version history

  1. Received: November 5, 2014
  2. Accepted: April 16, 2015
  3. Accepted Manuscript published: April 17, 2015 (version 1)
  4. Version of Record published: May 27, 2015 (version 2)

Copyright

© 2015, Gaviño 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. Michael A Gaviño
  2. Kevin J Ford
  3. Santiago Archila
  4. Graeme W Davis
(2015)
Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance
eLife 4:e05473.
https://doi.org/10.7554/eLife.05473

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https://doi.org/10.7554/eLife.05473

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