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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

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

doi

10.1016/j.celrep.2020.108338

subject

Has Abstract

pub_date

2020-11-03 00:00:00

pages

108338

issue

5

issn

2211-1247

pii

S2211-1247(20)31327-9

journal_volume

33

pub_type

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