Lateral septum drives differences in aggression in males and females

Aggression is a highly conserved behavior across species and a key component of social interactions for mammalian species, especially in competing for resources, defending territory, and establishing social status. However, aggression has been primarily studied in males and is under-studied in females. The social behavior neural network (SBNN) is a neural circuit thought to regulate a range of social behaviors, including aggression. Few studies have examined changes in the entire SBNN following aggression in both sexes. Both male and female Syrian hamsters (Mesocricetus auratus) readily exhibit territorial aggression, making them an excellent model for studying sex differences that underlie aggression. Many neuropsychiatric disorders are associated with sex differences in the prevalence and age of onset between males and females. Moreover, many neuropsychiatric disorders are associated with increased irritability, agitation, or aggression. Understanding the neural mechanisms that underlie aggression in both sexes will contribute to our understanding of neuropsychiatric disorders. Arginine-vasopressin (AVP) is a neuropeptide involved in regulating social behaviors, including social communication, social recognition, and aggression. The lateral septum (LS) is thought to regulate various social behaviors, including aggression. The LS seems to play an inhibitory role on aggression, with inhibition increasing aggression and LS stimulation decreasing aggression. AVP in the LS seems to be correlated with aggressive behavior in rats. Studies examining the role of AVP in the LS, however, were conducted almost exclusively in male rodents. We hypothesized that AVP in the LS differentially regulates aggression in males and females due to sex differences in the SBNN. Using c-Fos immunohistochemistry, we demonstrated that SBNN is sexually differentiated, showing sex-specific changes in neural activity following aggression in several regions of the SBNN, particularly in the posterior LS. Pharmacological manipulation of AVP 1a receptors in the dLS demonstrated that these differences may be mediated by AVP. We also confirmed the phenotype of the cells in the dLS and identified the LS-AH as a potential circuit mediating the sex-specific effects of AVP on aggression. These revealed that that the LS is critical to the differential regulation of aggression in females versus males, likely through the AVP system.