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November 13, 2020

Cerebellum-Specific Deletion of the GABAA Receptor d Subunit Leads to Sex-Specific Disruption of Behavior

Rudolph S, Guo C, Pashkovski SL, Osorno T, Gillis WF, Krauss JM, Nyitrai H, Flaquer I, El-Rifai M, Datta SR and Regehr WG. (2020)

Cerebellum-Specific Deletion of the GABAA Receptor d Subunit Leads to Sex-Specific Disruption of Behavior

Cell Reports 2020.108338

Granule cells (GCs) of the cerebellar input layer express high-affinity d GABAA subunit-containing GABAA receptors (dGABAARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of dGABAA (cerebellar [cb] d knockout [KO]) decreases tonic inhibition, makes GCs hyperexcitable, and inĀ  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 d KO mice display deficits in many behaviors, but motor function is normal. Strikingly, dGABAA deletion alters maternal behavior as well as spontaneous, stress-related, and social behaviors specifically in females. Our findings establish that dGABAARs 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.

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HISTORY SHOWS AGAIN AND AGAIN HOW NATURE POINTS OUT THE FOLLY OF MEN – “GODZILLA,” BLUE OYSTER CULT

Sandeep Robert Datta, MD, Ph.D Department of Neurobiology Harvard Medical School