A vasopressin circuit that modulates mouse social investigation and anxiety-like behavior in a sex-specific manner

• Published in: Proceedings of the National Academy of Sciences - PNAS 2024-05, Vol.121 (20), p.e2319641121-e2319641121
• Main Authors: Rigney, Nicole, Campos-Lira, Elba, Kirchner, Matthew K, Wei, Wei, Belkasim, Selma, Beaumont, Rachael, Singh, Sumeet, Suarez, Sara Guedez, Hartswick, Delenn, Stern, Javier E, de Vries, Geert J, Petrulis, Aras
• Format: Article
• Language: English
• Subjects: Animals; Anxiety; Anxiety - metabolism; Arginine Vasopressin - metabolism; Argipressin; Argipressin receptors; Behavior; Behavior, Animal - physiology; Biological Sciences; Brain; Cell differentiation; Circuits; Female; Females; Gender differences; Innervation; Male; Males; Mice; Mice, Inbred C57BL; Neurons - metabolism; Neurons - physiology; Optogenetics; Receptors, Vasopressin - genetics; Receptors, Vasopressin - metabolism; Septal Nuclei - metabolism; Septal Nuclei - physiology; Sex Characteristics; Sex differences; Sexual behavior; Social Behavior; Stimulation; Stria terminalis; Vasopressin; Vasopressins - metabolism; Vertebrates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2319641121

One of the largest sex differences in brain neurochemistry is the expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate brain, with males having more AVP cells in the bed nucleus of the stria terminalis (BNST) than females. Despite the long-standing implication of AVP in social and anxiety-like behaviors, the circuitry underlying AVP's control of these behaviors is still not well defined. Using optogenetic approaches, we show that inhibiting AVP BNST cells reduces social investigation in males, but not in females, whereas stimulating these cells increases social investigation in both sexes, but more so in males. These cells may facilitate male social investigation through their projections to the lateral septum (LS), an area with the highest density of sexually differentiated AVP innervation in the brain, as optogenetic stimulation of BNST AVP → LS increased social investigation and anxiety-like behavior in males but not in females; the same stimulation also caused a biphasic response of LS cells ex vivo. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated all these responses. Together, these findings establish a sexually differentiated role for BNST AVP cells in the control of social investigation and anxiety-like behavior, likely mediated by their projections to the LS.