Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium

Hiroko Bannai; Fumihiro Niwa; Mark W. Sherwood; Amulya Nidhi Shrivastava; Misa Arizono; Akitoshi Miyamoto; Kotomi Sugiura; Sabine Lévi; Antoine Triller; Katsuhiko Mikoshiba

doi:10.1016/j.celrep.2015.12.002

Bidirectional Control of Synaptic GABA_AR Clustering by Glutamate and Calcium

Hiroko Bannai, Fumihiro Niwa, Mark W. Sherwood, Amulya Nidhi Shrivastava, Misa Arizono, Akitoshi Miyamoto, Kotomi Sugiura, Sabine Lévi, Antoine Triller^*, Katsuhiko Mikoshiba

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

62 Citations (Scopus)

Abstract

GABAergic synaptic transmission regulates brain function by establishing the appropriate excitationinhibition (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_AR) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP₃ receptor-dependent calcium release and protein kinase C to promote GABA_AR clustering and GABAergic transmission. This GABA_AR 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.

Original language	English
Pages (from-to)	2768-2780
Number of pages	13
Journal	Cell Reports
Volume	13
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2015.12.002
Publication status	Published - 2015
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2015.12.002

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@article{cc4535a6978f4e9ebc32d2c1bd38c0ab,

title = "Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium",

abstract = "GABAergic synaptic transmission regulates brain function by establishing the appropriate excitationinhibition (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 GABAA receptor (GABAAR) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABAAR clustering and GABAergic transmission. This GABAAR 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.",

author = "Hiroko Bannai and Fumihiro Niwa and Sherwood, {Mark W.} and Shrivastava, {Amulya Nidhi} and Misa Arizono and Akitoshi Miyamoto and Kotomi Sugiura and Sabine L{\'e}vi and Antoine Triller and Katsuhiko Mikoshiba",

note = "Funding Information: We thank the Research Resource Center (RIKEN BSI) for FANTOM3 clone and for supporting antibody production. We thank C. Hisatsune and S. Sakuragi for technical supports; T. Inoue, M. Dahan, V. Racine, and J.B. Sibarita for the analysis program; and Y. Oda, I. Mori, C. Yokoyama, and A.V. Terashima for their valuable comments on the manuscript. This work was supported by RIKEN (Special Postdoctoral Researcher [SPDR] and Foreign Postdoctoral Researcher [FPR] programs); KAKENHI (20700300, 25830058, 20220007, and “Glial assembly” 26117509); Japan Society for the Promotion of Science (JSPS, 06J06775); research grants from the Toyobo Biotechnology Foundation, Kato Memorial Bioscience Foundation, and Toray Science Foundation; and the Moritani Scholarship Foundation. Work in the A.T. laboratory was supported by the European Research Council (ERC) grant PlastInhib and the L{\textquoteright}Agence Nationale de la Recherche (ANR) grant Synaptune, The Labex Memolife (ANR-10-LABX-54) and PSL Research University (ANR-11-IDEX-0001-02). We thank two anonymous reviewers for their insightful and constructive comments on the manuscript. Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

doi = "10.1016/j.celrep.2015.12.002",

language = "English",

volume = "13",

pages = "2768--2780",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

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T1 - Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium

AU - Bannai, Hiroko

AU - Niwa, Fumihiro

AU - Sherwood, Mark W.

AU - Shrivastava, Amulya Nidhi

AU - Arizono, Misa

AU - Miyamoto, Akitoshi

AU - Sugiura, Kotomi

AU - Lévi, Sabine

AU - Triller, Antoine

AU - Mikoshiba, Katsuhiko

N1 - Funding Information: We thank the Research Resource Center (RIKEN BSI) for FANTOM3 clone and for supporting antibody production. We thank C. Hisatsune and S. Sakuragi for technical supports; T. Inoue, M. Dahan, V. Racine, and J.B. Sibarita for the analysis program; and Y. Oda, I. Mori, C. Yokoyama, and A.V. Terashima for their valuable comments on the manuscript. This work was supported by RIKEN (Special Postdoctoral Researcher [SPDR] and Foreign Postdoctoral Researcher [FPR] programs); KAKENHI (20700300, 25830058, 20220007, and “Glial assembly” 26117509); Japan Society for the Promotion of Science (JSPS, 06J06775); research grants from the Toyobo Biotechnology Foundation, Kato Memorial Bioscience Foundation, and Toray Science Foundation; and the Moritani Scholarship Foundation. Work in the A.T. laboratory was supported by the European Research Council (ERC) grant PlastInhib and the L’Agence Nationale de la Recherche (ANR) grant Synaptune, The Labex Memolife (ANR-10-LABX-54) and PSL Research University (ANR-11-IDEX-0001-02). We thank two anonymous reviewers for their insightful and constructive comments on the manuscript. Publisher Copyright: © 2015 The Authors.

PY - 2015

Y1 - 2015

N2 - GABAergic synaptic transmission regulates brain function by establishing the appropriate excitationinhibition (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 GABAA receptor (GABAAR) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABAAR clustering and GABAergic transmission. This GABAAR 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.

AB - GABAergic synaptic transmission regulates brain function by establishing the appropriate excitationinhibition (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 GABAA receptor (GABAAR) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABAAR clustering and GABAergic transmission. This GABAAR 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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DO - 10.1016/j.celrep.2015.12.002

M3 - Article

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AN - SCOPUS:84969722278

SN - 2211-1247

VL - 13

SP - 2768

EP - 2780

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -

Bidirectional Control of Synaptic GABA_AR Clustering by Glutamate and Calcium

Abstract

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