Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses

Abstract
Data availability
Article and author information
Metrics

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 GABA_AR 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 GABA_ARs 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

Patricia M Horvath

Department of Pharmacology, Vanderbilt University, Nashville, United States

Competing interests
No competing interests declared.
Michelle K Piazza

Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States

Competing interests
No competing interests declared.
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.

"This ORCID iD identifies the author of this article:" 0000-0003-0018-501X
Ege T Kavalali

Department of Pharmacology, Vanderbilt University, Nashville, United States

For correspondence
ege.kavalali@vanderbilt.edu

Competing interests
No competing interests declared.

"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

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.