Work

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

Year: 2021

Type: article

Abstract: Tonic inhibition mediated by extrasynaptic γ-aminobutyric acid type A receptors (GABA A Rs) 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 A R-mediated tonic currents are significantly reduced. Mechanistically, Shisa7 is crucial for α5-GABA A R 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. Interestingly, in young adult Shisa7 KOs, basal tonic inhibition in hippocampal neurons is unaltered, largely due to the diminished α5-GABA A R component of tonic inhibition. However, at this stage, tonic inhibition oscillates during the daily sleep/wake cycle, a process requiring Shisa7. Together, these data demonstrate that intricate signaling mechanisms regulate tonic inhibition at different developmental stages and reveal a molecular link between sleep and tonic inhibition.

Source: Cell Reports

DOI: 10.1016/j.celrep.2021.108899

Authors: Kunwei Wu, Wenyan Han, Qingjun Tian, Yan Li, Wei Lu

Institutions: National Institutes of Health, National Institute of Neurological Disorders and Stroke

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,200