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Cerebellum-Specific Deletion of the GABAAReceptor δ Subunit Leads to Sex-Specific Disruption of Behavior
- Source :
- Cell Reports; November 2020, Vol. 33 Issue: 5
- Publication Year :
- 2020
-
Abstract
- Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABAAsubunit-containing GABAAreceptors (δGABAARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of δGABAA(cerebellar [cb] δ 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 δ KO mice display deficits in many behaviors, but motor function is normal. Strikingly, δGABAAdeletion alters maternal behavior as well as spontaneous, stress-related, and social behaviors specifically in females. Our findings establish that δGABAARs 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.
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 33
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Cell Reports
- Publication Type :
- Periodical
- Accession number :
- ejs54551515
- Full Text :
- https://doi.org/10.1016/j.celrep.2020.108338