Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection.

ABSTRACT: Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABA_A receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LH^GABA) neurons. This was associated with LH^GABA neuron hyperexcitability and impaired hippocampal long-term potentiation, through a monosynaptic LH^GABA to CA3^GABA projection. Optogenetic activation of this projection caused

SUBMITTER: Zhou W 

PROVIDER: S-EPMC6361549 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature