The paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior in mice.

ABSTRACT: Bed nucleus of the stria terminalis (BNST) neurons that synthesize corticotropin-releasing factor (CRF) drive binge alcohol drinking and anxiety. Here, we found that female C57BL/6J mice binge drink more than males and have greater basal BNST^CRF neuron excitability and synaptic excitation. We identified a dense VGLUT2 + synaptic input from the paraventricular thalamus (PVT) that releases glutamate directly onto BNST^CRF neurons but also engages a large BNST interneuron population to ultimately inhibit BNST^CRF neurons, and this polysynaptic PVT^VGLUT2-BNST^CRF circuit is more robust in females than males. Chemogenetic inhibition of the PVT^BNST projection promoted binge alcohol drinking only in female mice, while activation reduc

SUBMITTER: Levine OB 

PROVIDER: S-EPMC8382748 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature