A vasopressin circuit that modulates sex-specific social interest and anxiety-like behavior in mice

• Authors: Nicole Rigney, Emory University; Elba Campos-Lira, Georgia State University; Matthew K. Kirchner, Georgia State University; Wei Wei, Georgia State University; Selma Belkasim, Yale University; Rachael Beaumont, Cornell University; Sumeet Singh, Georgia State University; Geert J. de Vries, Georgia State University; Aras Petrulis, Georgia State University
• Journal Title: bioRxiv
• Publisher: NIH | 2023-11-09, Pages 564847-None
• Type of Work: Article | Preprint: Prior to Peer Review
• Publisher DOI: http://doi.org/10.1101/2023.11.06.564847
• Subjects: Biology, Neuroscience; Health Sciences, Public Health
• Keywords: sex differences; brain neurochemistry; neuropeptide arginine vasopressin; male-biased expression

Abstract

One of the largest sex differences in brain neurochemistry is the male-biased expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate social brain. Despite the long-standing implication of AVP in social and anxiety-like behavior, the precise circuitry and anatomical substrate underlying its control are still poorly understood. By employing optogenetic manipulation of AVP cells within the bed nucleus of the stria terminalis (BNST), we have unveiled a central role for these cells in promoting social investigation, with a more pronounced role in males relative to females. These cells facilitate male social investigation and anxiety-like behavior through their projections to the lateral septum (LS), an area with the highest density of sexually-dimorphic AVP fibers. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated stimulation-mediated increases in these behaviors. Together, these findings establish a distinct BNST AVP → LS V1aR circuit that modulates sex-specific social interest and anxiety-like behavior.