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Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus
Recent molecular studies suggest that the expression levels of δ and γ2 GABA(A) receptor (GABA(A)R) subunits regulate the balance between synaptic and extrasynaptic GABA neurotransmission in multiple brain regions. We investigated the expression of GABA(A)δ and GABA(A)γ2 and the functional significa...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411165/ https://www.ncbi.nlm.nih.gov/pubmed/28466071 http://dx.doi.org/10.1523/ENEURO.0352-16.2017 |
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author | Walton, James C. McNeill, John K. Oliver, Khallyl A. Albers, H. Elliott |
author_facet | Walton, James C. McNeill, John K. Oliver, Khallyl A. Albers, H. Elliott |
author_sort | Walton, James C. |
collection | PubMed |
description | Recent molecular studies suggest that the expression levels of δ and γ2 GABA(A) receptor (GABA(A)R) subunits regulate the balance between synaptic and extrasynaptic GABA neurotransmission in multiple brain regions. We investigated the expression of GABA(A)δ and GABA(A)γ2 and the functional significance of a change in balance between these subunits in a robust local GABA network contained within the suprachiasmatic nucleus of the hypothalamus (SCN). Muscimol, which can activate both synaptic and extrasynaptic GABA(A)Rs, injected into the SCN during the day phase advanced the circadian pacemaker, whereas injection of the extrasynaptic GABA(A) superagonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) had no effect on circadian phase. In contrast, injection of either THIP or muscimol during the night was sufficient to block the phase shifting effects of light. Gene expression analysis of the whole SCN revealed different temporal patterns in GABA(A)δ and GABA(A)γ2 mRNA expression. When examined across all subregions of the SCN, quantitative immunohistochemical analysis found no significant variations in GABA(A)δ protein immunoreactivity (IR) but did find significant variations in GABA(A)γ2 protein-IR in hamsters housed in either LD cycles or in constant darkness. Remarkably, significant interactions in the ratio of GABA(A)δ:GABA(A)γ2 subunits between lighting condition and circadian phase occurred only within one highly discrete anatomical area of the SCN; a region that functions as the input for lighting information from the retina. Taken together, these data support the hypothesis that the balance between synaptic and extrasynaptic GABA(A)Rs determines the functional response to GABA, and that this balance is differentially regulated in a region-specific manner. |
format | Online Article Text |
id | pubmed-5411165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-54111652017-05-02 Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus Walton, James C. McNeill, John K. Oliver, Khallyl A. Albers, H. Elliott eNeuro New Research Recent molecular studies suggest that the expression levels of δ and γ2 GABA(A) receptor (GABA(A)R) subunits regulate the balance between synaptic and extrasynaptic GABA neurotransmission in multiple brain regions. We investigated the expression of GABA(A)δ and GABA(A)γ2 and the functional significance of a change in balance between these subunits in a robust local GABA network contained within the suprachiasmatic nucleus of the hypothalamus (SCN). Muscimol, which can activate both synaptic and extrasynaptic GABA(A)Rs, injected into the SCN during the day phase advanced the circadian pacemaker, whereas injection of the extrasynaptic GABA(A) superagonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) had no effect on circadian phase. In contrast, injection of either THIP or muscimol during the night was sufficient to block the phase shifting effects of light. Gene expression analysis of the whole SCN revealed different temporal patterns in GABA(A)δ and GABA(A)γ2 mRNA expression. When examined across all subregions of the SCN, quantitative immunohistochemical analysis found no significant variations in GABA(A)δ protein immunoreactivity (IR) but did find significant variations in GABA(A)γ2 protein-IR in hamsters housed in either LD cycles or in constant darkness. Remarkably, significant interactions in the ratio of GABA(A)δ:GABA(A)γ2 subunits between lighting condition and circadian phase occurred only within one highly discrete anatomical area of the SCN; a region that functions as the input for lighting information from the retina. Taken together, these data support the hypothesis that the balance between synaptic and extrasynaptic GABA(A)Rs determines the functional response to GABA, and that this balance is differentially regulated in a region-specific manner. Society for Neuroscience 2017-05-01 /pmc/articles/PMC5411165/ /pubmed/28466071 http://dx.doi.org/10.1523/ENEURO.0352-16.2017 Text en Copyright © 2017 Walton et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | New Research Walton, James C. McNeill, John K. Oliver, Khallyl A. Albers, H. Elliott Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus |
title | Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus |
title_full | Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus |
title_fullStr | Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus |
title_full_unstemmed | Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus |
title_short | Temporal Regulation of GABA(A) Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus |
title_sort | temporal regulation of gaba(a) receptor subunit expression: role in synaptic and extrasynaptic communication in the suprachiasmatic nucleus |
topic | New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411165/ https://www.ncbi.nlm.nih.gov/pubmed/28466071 http://dx.doi.org/10.1523/ENEURO.0352-16.2017 |
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