Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits.

ABSTRACT: Loss-of-function mutations of the gene Cul3 have been identified as a risk factor for autism-spectrum disorder (ASD), but the pathogenic mechanisms are not well understood. Conditional Cul3 ablation in cholinergic neurons of mice (Chat^CRECul3^F/+) recapitulated ASD-like social and sensory gating phenotypes and caused significant cognitive impairments, with diminished activity of cholinergic neurons in the basal forebrain (BF). Chemogenetic inhibition of BF cholinergic neurons in healthy mice induced similar social and cognitive deficits. Conversely, chemogenetic stimulation of BF cholinergic neurons in Chat^CRECul3^F/+ mice reversed abnormalities in sensory gating and cognition. Cortical hypofunction was also found after ChAT-specific Cul3 ablation

SUBMITTER: Rapanelli M 

PROVIDER: S-EPMC9873627 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature