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

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)

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.

Metrics

  • 5,681
    views
  • 598
    downloads
  • 26
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Patricia M Horvath
  2. Michelle K Piazza
  3. Lisa M Monteggia
  4. Ege T Kavalali
(2020)
Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
eLife 9:e52852.
https://doi.org/10.7554/eLife.52852

Share this article

https://doi.org/10.7554/eLife.52852

Further reading

    1. Neuroscience
    David C Williams, Amanda Chu ... Michael A McDannald
    Research Advance

    Recognizing and responding to threat cues is essential to survival. Freezing is a predominant threat behavior in rats. We have recently shown that a threat cue can organize diverse behaviors beyond freezing, including locomotion (Chu et al., 2024). However, that experimental design was complex, required many sessions, and had rats receive many foot shock presentations. Moreover, the findings were descriptive. Here, we gave female and male Long Evans rats cue light illumination paired or unpaired with foot shock (8 total) in a conditioned suppression setting, using a range of shock intensities (0.15, 0.25, 0.35, or 0.50 mA). We found that conditioned suppression was only observed at higher foot shock intensities (0.35 mA and 0.50 mA). We constructed comprehensive temporal ethograms by scoring 22,272 frames across 12 behavior categories in 200-ms intervals around cue light illumination. The 0.50 mA and 0.35 mA shock-paired visual cues suppressed reward seeking, rearing, and scaling, as well as light-directed rearing and light-directed scaling. The shock-paired visual cue further elicited locomotion and freezing. Linear discriminant analyses showed that ethogram data could accurately classify rats into paired and unpaired groups. Using complete ethogram data produced superior classification compared to behavior subsets, including an Immobility subset featuring freezing. The results demonstrate diverse threat behaviors – in a short and simple procedure – containing sufficient information to distinguish the visual fear conditioning status of individual rats.

    1. Neuroscience
    Agnieszka Glica, Katarzyna Wasilewska ... Katarzyna Jednoróg
    Research Article

    The neural noise hypothesis of dyslexia posits an imbalance between excitatory and inhibitory (E/I) brain activity as an underlying mechanism of reading difficulties. This study provides the first direct test of this hypothesis using both electroencephalography (EEG) power spectrum measures in 120 Polish adolescents and young adults (60 with dyslexia, 60 controls) and glutamate (Glu) and gamma-aminobutyric acid (GABA) concentrations from magnetic resonance spectroscopy (MRS) at 7T MRI scanner in half of the sample. Our results, supported by Bayesian statistics, show no evidence of E/I balance differences between groups, challenging the hypothesis that cortical hyperexcitability underlies dyslexia. These findings suggest that alternative mechanisms must be explored and highlight the need for further research into the E/I balance and its role in neurodevelopmental disorders.