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The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type

The diversity of GABA(A) receptor (GABA(A)R) subunits and the numerous configurations during subunit assembly give rise to a variety of receptors with different functional properties. This heterogeneity results in variations in GABAergic conductances across numerous brain regions and cell types. Pha...

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Detalles Bibliográficos
Autores principales: Lee, Vallent, Maguire, Jamie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909947/
https://www.ncbi.nlm.nih.gov/pubmed/24550784
http://dx.doi.org/10.3389/fncir.2014.00003
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author Lee, Vallent
Maguire, Jamie
author_facet Lee, Vallent
Maguire, Jamie
author_sort Lee, Vallent
collection PubMed
description The diversity of GABA(A) receptor (GABA(A)R) subunits and the numerous configurations during subunit assembly give rise to a variety of receptors with different functional properties. This heterogeneity results in variations in GABAergic conductances across numerous brain regions and cell types. Phasic inhibition is mediated by synaptically-localized receptors with a low affinity for GABA and results in a transient, rapidly desensitizing GABAergic conductance; whereas, tonic inhibition is mediated by extrasynaptic receptors with a high affinity for GABA and results in a persistent GABAergic conductance. The specific functions of tonic versus phasic GABAergic inhibition in different cell types and the impact on specific neural circuits are only beginning to be unraveled. Here we review the diversity in the magnitude of tonic GABAergic inhibition in various brain regions and cell types, and highlight the impact on neuronal excitability in different neuronal circuits. Further, we discuss the relevance of tonic inhibition in various physiological and pathological contexts as well as the potential of targeting these receptor subtypes for treatment of diseases, such as epilepsy.
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spelling pubmed-39099472014-02-18 The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type Lee, Vallent Maguire, Jamie Front Neural Circuits Neuroscience The diversity of GABA(A) receptor (GABA(A)R) subunits and the numerous configurations during subunit assembly give rise to a variety of receptors with different functional properties. This heterogeneity results in variations in GABAergic conductances across numerous brain regions and cell types. Phasic inhibition is mediated by synaptically-localized receptors with a low affinity for GABA and results in a transient, rapidly desensitizing GABAergic conductance; whereas, tonic inhibition is mediated by extrasynaptic receptors with a high affinity for GABA and results in a persistent GABAergic conductance. The specific functions of tonic versus phasic GABAergic inhibition in different cell types and the impact on specific neural circuits are only beginning to be unraveled. Here we review the diversity in the magnitude of tonic GABAergic inhibition in various brain regions and cell types, and highlight the impact on neuronal excitability in different neuronal circuits. Further, we discuss the relevance of tonic inhibition in various physiological and pathological contexts as well as the potential of targeting these receptor subtypes for treatment of diseases, such as epilepsy. Frontiers Media S.A. 2014-02-03 /pmc/articles/PMC3909947/ /pubmed/24550784 http://dx.doi.org/10.3389/fncir.2014.00003 Text en Copyright © 2014 Lee and Maguire. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Lee, Vallent
Maguire, Jamie
The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type
title The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type
title_full The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type
title_fullStr The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type
title_full_unstemmed The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type
title_short The impact of tonic GABA(A) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type
title_sort impact of tonic gaba(a) receptor-mediated inhibition on neuronal excitability varies across brain region and cell type
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909947/
https://www.ncbi.nlm.nih.gov/pubmed/24550784
http://dx.doi.org/10.3389/fncir.2014.00003
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