Abstract
Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABAA subunit-containing GABAA receptors (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, δGABAA deletion 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. Rudolph et al. show that deletion of the neuromodulator and hormone-sensitive δGABAA receptor subunit from cerebellar granule cells results in anxiety-like behaviors and female-specific deficits in social behavior and maternal care. δGABAA deletion is associated with hyperexcitability of the cerebellar input layer and altered activation of many stress-related brain regions.
Original language | English (US) |
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Article number | 108338 |
Journal | Cell Reports |
Volume | 33 |
Issue number | 5 |
DOIs | |
State | Published - Nov 3 2020 |
Externally published | Yes |
Keywords
- GABA
- anxiety-like behavior
- cerebellum
- hyperexcitability
- maternal behavior
- social behavior
- stress
- tonic inhibition
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology