Cerebellum-Specific Deletion of the GABA_A Receptor ? Subunit Leads to Sex-Specific Disruption of Behavior.

ABSTRACT: Granule cells (GCs) of the cerebellar input layer express high-affinity ? GABA_A subunit-containing GABA_A receptors (?GABA_ARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of ?GABA_A (cerebellar [cb] ? knockout [KO]) decreases tonic inhibition, makes GCs hyperexcitable, and in turn, leads to differential activation of cb output regions as well as many cortical and subcortical brain areas involved in cognition, anxiety-like behaviors, and the stress response. Cb ? KO mice display deficits in many behaviors, but motor function is normal. Strikingly, ?GABA_A deletion alters maternal behavior as well as spontaneous, stress-related, and social behaviors specifically in females. Our findings establish that ?GABA_ARs enable the cerebellum to control diverse behaviors not previously associated with the cerebellum in a sex-dependent manner. These insights may contribute to a better understanding of the mechanisms that underlie behavioral abnormalities in psychiatric and neurodevelopmental disorders that display a gender bias.

SUBMITTER: Rudolph S 

PROVIDER: S-EPMC7700496 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature