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
Affiliations
Hiroko Bannai
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Fumihiro Niwa
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Mark W. Sherwood
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Amulya Nidhi Shrivastava
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
Misa Arizono
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Akitoshi Miyamoto
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Kotomi Sugiura
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Sabine Lévi
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
Antoine Triller
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
Katsuhiko Mikoshiba
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
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.
