Activity- and sleep-dependent regulation of tonic inhibition by Shisa7.

ABSTRACT: Tonic inhibition mediated by extrasynaptic γ-aminobutyric acid type A receptors (GABA_ARs) critically regulates neuronal excitability and brain function. However, the mechanisms regulating tonic inhibition remain poorly understood. Here, we report that Shisa7 is critical for tonic inhibition regulation in hippocampal neurons. In juvenile Shisa7 knockout (KO) mice, α5-GABA_AR-mediated tonic currents are significantly reduced. Mechanistically, Shisa7 is crucial for α5-GABA_AR exocytosis. Additionally, Shisa7 regulation of tonic inhibition requires protein kinase A (PKA) that phosphorylates Shisa7 serine 405 (S405). Importantly, tonic inhibition undergoes activity-dependent regulation, and Shisa7 is required for homeostatic potentiation of tonic inhibition. Inter

SUBMITTER: Wu K 

PROVIDER: S-EPMC8025742 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature