title: Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium.
abstract: 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 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.
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8602, Japan; Nagoya Research Center for Brain & Neural Circuits, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8602, Japan; École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM, CNRS, Ecole Normale Supérieure, PSL Research University, 46 rue d'Ulm, 75005 Paris, France.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Bannai
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Niwa
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Sherwood
authors.affiliation: École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM, CNRS, Ecole Normale Supérieure, PSL Research University, 46 rue d'Ulm, 75005 Paris, France.
authors.forename: Amulya Nidhi
authors.initials: AN
authors.lastname: Shrivastava
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Arizono
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Miyamoto
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kotomi
authors.initials: K
authors.lastname: Sugiura
authors.affiliation: École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM, CNRS, Ecole Normale Supérieure, PSL Research University, 46 rue d'Ulm, 75005 Paris, France; Institut du Fer à Moulin, INSERM, Unité Mixte de Recherche-S 839, Sorbonne Universités, Université Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Lévi
authors.affiliation: École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), INSERM, CNRS, Ecole Normale Supérieure, PSL Research University, 46 rue d'Ulm, 75005 Paris, France. Electronic address: triller@biologie.ens.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Triller
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: mikosiba@brain.riken.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A; D018698:Glutamic Acid; D002118:Calcium