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Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium

GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I) balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promot...

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Autores principales: Bannai, Hiroko, Niwa, Fumihiro, Sherwood, Mark W., Shrivastava, Amulya Nidhi, Arizono, Misa, Miyamoto, Akitoshi, Sugiura, Kotomi, Lévi, Sabine, Triller, Antoine, Mikoshiba, Katsuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700050/
https://www.ncbi.nlm.nih.gov/pubmed/26711343
http://dx.doi.org/10.1016/j.celrep.2015.12.002
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author Bannai, Hiroko
Niwa, Fumihiro
Sherwood, Mark W.
Shrivastava, Amulya Nidhi
Arizono, Misa
Miyamoto, Akitoshi
Sugiura, Kotomi
Lévi, Sabine
Triller, Antoine
Mikoshiba, Katsuhiko
author_facet Bannai, Hiroko
Niwa, Fumihiro
Sherwood, Mark W.
Shrivastava, Amulya Nidhi
Arizono, Misa
Miyamoto, Akitoshi
Sugiura, Kotomi
Lévi, Sabine
Triller, Antoine
Mikoshiba, Katsuhiko
author_sort Bannai, Hiroko
collection PubMed
description GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I) balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promote the restorative homeostatic stabilization of GABAergic synapses remain unknown. Here, by quantum dot single-particle tracking, we characterize a signaling pathway that promotes the stability of GABA(A) receptor (GABA(A)R) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP(3) receptor-dependent calcium release and protein kinase C to promote GABA(A)R clustering and GABAergic transmission. This GABA(A)R stabilization pathway counteracts the rapid cluster dispersion caused by glutamate-driven NMDA receptor-dependent calcium influx and calcineurin dephosphorylation, including in conditions of pathological glutamate toxicity. These findings show that glutamate activates distinct receptors and spatiotemporal patterns of calcium signaling for opposing control of GABAergic synapses.
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spelling pubmed-47000502016-01-11 Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium Bannai, Hiroko Niwa, Fumihiro Sherwood, Mark W. Shrivastava, Amulya Nidhi Arizono, Misa Miyamoto, Akitoshi Sugiura, Kotomi Lévi, Sabine Triller, Antoine Mikoshiba, Katsuhiko Cell Rep Article GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I) balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promote the restorative homeostatic stabilization of GABAergic synapses remain unknown. Here, by quantum dot single-particle tracking, we characterize a signaling pathway that promotes the stability of GABA(A) receptor (GABA(A)R) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP(3) receptor-dependent calcium release and protein kinase C to promote GABA(A)R clustering and GABAergic transmission. This GABA(A)R stabilization pathway counteracts the rapid cluster dispersion caused by glutamate-driven NMDA receptor-dependent calcium influx and calcineurin dephosphorylation, including in conditions of pathological glutamate toxicity. These findings show that glutamate activates distinct receptors and spatiotemporal patterns of calcium signaling for opposing control of GABAergic synapses. Cell Press 2015-12-17 /pmc/articles/PMC4700050/ /pubmed/26711343 http://dx.doi.org/10.1016/j.celrep.2015.12.002 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Bannai, Hiroko
Niwa, Fumihiro
Sherwood, Mark W.
Shrivastava, Amulya Nidhi
Arizono, Misa
Miyamoto, Akitoshi
Sugiura, Kotomi
Lévi, Sabine
Triller, Antoine
Mikoshiba, Katsuhiko
Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium
title Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium
title_full Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium
title_fullStr Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium
title_full_unstemmed Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium
title_short Bidirectional Control of Synaptic GABA(A)R Clustering by Glutamate and Calcium
title_sort bidirectional control of synaptic gaba(a)r clustering by glutamate and calcium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700050/
https://www.ncbi.nlm.nih.gov/pubmed/26711343
http://dx.doi.org/10.1016/j.celrep.2015.12.002
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