Amygdala AVPR1A mediates susceptibility to chronic social isolation in females

Abstract

Females are more sensitive to social exclusion, which could contribute to their heightened susceptibility to anxiety disorders. Chronic social isolation stress (CSIS) for at least 7 weeks after puberty induces anxiety-related behavioral adaptations in female mice. Here, we show that Arginine vasopressin receptor 1a (Avpr1a)-expressing neurons in the central nucleus of the amygdala (CeA) mediate these sex-specific effects, in part, via projections to the caudate putamen. Loss of function studies demonstrate that AVPR1A signaling in the CeA is required for effects of CSIS on anxiety-related behaviors in females but has no effect in males or group housed females. This sex-specificity is mediated by AVP produced by a subpopulation of neurons in the posterodorsal medial nucleus of the amygdala that project to the CeA. Estrogen receptor alpha signaling in these neurons also contributes to preferential sensitivity of females to CSIS. These data support new therapeutic applications for AVPR1A antagonists in women.

Inputs and Outputs of the Mammalian Circadian Clock

“…AVP axons project sparsely to the lateral septum, AHN, BNST, VLPO, MPOA, MPN, PeVN, LHb, LH, VMH, PH, and SON. A recent study also identified monosynaptic projections from a small number of SCN AVP neurons to the central amygdala [ 121 ]. Axons from PK2 neurons project prominently to the lateral septum, MPOA, OVLT, PVN, LH, and periaqueductal gray.…”