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

Research output: Contribution to journalArticle

46 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 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.

Original languageEnglish
Pages (from-to)2768-2780
Number of pages13
JournalCell Reports
Volume13
Issue number12
DOIs
Publication statusPublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Bannai, H., Niwa, F., Sherwood, M. W., Shrivastava, A. N., Arizono, M., Miyamoto, A., Sugiura, K., Lévi, S., Triller, A., & Mikoshiba, K. (2015). Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium. Cell Reports, 13(12), 2768-2780. https://doi.org/10.1016/j.celrep.2015.12.002