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Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses

  1. Patricia M Horvath
  2. Michelle K Piazza
  3. Lisa M Monteggia  Is a corresponding author
  4. Ege T Kavalali  Is a corresponding author
  1. Vanderbilt University, United States
Research Article
  • Cited 3
  • Views 2,593
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Cite this article as: eLife 2020;9:e52852 doi: 10.7554/eLife.52852

Abstract

Synaptic transmission is initiated via spontaneous or action-potential evoked fusion of synaptic vesicles. At excitatory synapses, glutamatergic receptors activated by spontaneous and evoked neurotransmission are segregated. Although inhibitory synapses also transmit signals spontaneously or in response to action potentials, they differ from excitatory synapses in both structure and function. Therefore, we hypothesized that inhibitory synapses may have different organizing principles. We report picrotoxin, a GABAAR antagonist, blocks neurotransmission in a use-dependent manner at rat hippocampal synapses and therefore can be used to interrogate synaptic properties. Using this tool, we uncovered partial segregation of inhibitory spontaneous and evoked neurotransmission. We found up to 40% of the evoked response is mediated through GABAARs which are only activated by evoked neurotransmission. These data indicate GABAergic spontaneous and evoked neurotransmission processes are partially non-overlapping, suggesting they may serve divergent roles in neuronal signaling.

Data availability

All source data files are included in the manuscript and supporting files.

Article and author information

Author details

  1. Patricia M Horvath

    Department of Pharmacology, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  2. Michelle K Piazza

    Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  3. Lisa M Monteggia

    Department of Neuroscience, Vanderbilt University, Nashville, United States
    For correspondence
    lisa.monteggia@vanderbilt.edu
    Competing interests
    Lisa M Monteggia, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0018-501X
  4. Ege T Kavalali

    Department of Pharmacology, Vanderbilt University, Nashville, United States
    For correspondence
    ege.kavalali@vanderbilt.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1777-227X

Funding

National Institute of General Medical Sciences (T32 GM008203)

  • Patricia M Horvath

National Institute of Mental Health (R01 MH070727)

  • Lisa M Monteggia

National Institute of Mental Health (R01 MH66198)

  • Ege T Kavalali

National Institute of Mental Health (T32MH064913)

  • Michelle K Piazza

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

Ethics

Animal experimentation: Animal procedures conformed to the Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at UT Southwestern Medical Center ( Animal Protocol Number APN 2016-101416) and at Vanderbilt University School of Medicine (Animal Protocol Number M1800103)

Reviewing Editor

  1. John Huguenard, Stanford University School of Medicine, United States

Publication history

  1. Received: October 18, 2019
  2. Accepted: May 13, 2020
  3. Accepted Manuscript published: May 13, 2020 (version 1)
  4. Version of Record published: May 26, 2020 (version 2)

Copyright

© 2020, Horvath 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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