Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses

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 resp...

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Main Authors: Patricia M Horvath, Michelle K Piazza, Lisa M Monteggia, Ege T Kavalali
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-05-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/52852
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author Patricia M Horvath
Michelle K Piazza
Lisa M Monteggia
Ege T Kavalali
author_facet Patricia M Horvath
Michelle K Piazza
Lisa M Monteggia
Ege T Kavalali
author_sort Patricia M Horvath
collection DOAJ
description 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.
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spelling doaj.art-5d42b65ad1034437a3ace174f99c440f2022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.52852Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapsesPatricia M Horvath0https://orcid.org/0000-0001-9969-8637Michelle K Piazza1https://orcid.org/0000-0002-7852-3456Lisa M Monteggia2https://orcid.org/0000-0003-0018-501XEge T Kavalali3https://orcid.org/0000-0003-1777-227XDepartment of Pharmacology, Vanderbilt University, Nashville, United States; Department of Neuroscience, the University of Texas Southwestern Medical Center, Dallas, United StatesVanderbilt Brain Institute, Vanderbilt University, Nashville, United States; Neuroscience Program, Vanderbilt University, Nashville, United StatesDepartment of Pharmacology, Vanderbilt University, Nashville, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, United StatesDepartment of Pharmacology, Vanderbilt University, Nashville, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, United StatesSynaptic 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.https://elifesciences.org/articles/52852spontaneous releaseGABAergic neurotransmissionpicrotoxin
spellingShingle Patricia M Horvath
Michelle K Piazza
Lisa M Monteggia
Ege T Kavalali
Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
eLife
spontaneous release
GABAergic neurotransmission
picrotoxin
title Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
title_full Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
title_fullStr Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
title_full_unstemmed Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
title_short Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
title_sort spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
topic spontaneous release
GABAergic neurotransmission
picrotoxin
url https://elifesciences.org/articles/52852
work_keys_str_mv AT patriciamhorvath spontaneousandevokedneurotransmissionarepartiallysegregatedatinhibitorysynapses
AT michellekpiazza spontaneousandevokedneurotransmissionarepartiallysegregatedatinhibitorysynapses
AT lisammonteggia spontaneousandevokedneurotransmissionarepartiallysegregatedatinhibitorysynapses
AT egetkavalali spontaneousandevokedneurotransmissionarepartiallysegregatedatinhibitorysynapses