Dissecting Oxytocin Neural Circuits Involved in Prosocial Behavior

Project Summary Social affiliation is critical to the physical and emotional health of a wide variety of species. Disruptions in social functioning - a key feature of conditions like autism, social anxiety, and schizophrenia - can severely limit one's capacity to cultivate healthy social relationships and bonds. The neural circuit mechanisms governing affiliative social behaviors are not well understood, which is an important part of the social processes domain of the Research Domain Criteria (RDoC) and relevant to several psychiatric disorders. Allogrooming (grooming behavior directed toward another individual) is a major form of affiliative social contact through which animals may form, maintain, and strengthen social relationships and is conserved in a wide range of social species, such as birds, bats, rodents, canids, cats, equids, and primates. This project aims to understand the neural mechanisms regulating allogrooming in mice by examining the oxytocin receptor (OXTR) system, a critical modulator within the brain's `social behavior network'. The sponsor has previously identified a pathway from the medial amygdala (MeA) to the medial preoptic area (MPOA) as essential for allogrooming in mice. However, the specific neural encoding of oxytocin-responsive neurons in this circuit remains unknown. I will gain exceptional training in powerful genetic approaches that allow us to target oxytocin receptor cells specifically. The outlined proposal will 1) utilize in vivo optogenetics to manipulate oxytocin-sensitive MeA neurons and their projections to the MPOA and BNST, 2) assess the role of OXTR specifically in the MeA on prosocial behavior, and 3) utilize in vivo freely moving calcium imaging to optically record MeA OXTR neurons during allogrooming behavior. The proposed study will provide an excellent training experience for the applicant, and it will reveal how discrete, anatomically defined pathways descending from the MeA are engaged during allogrooming. These results will set the foundation for a more incisive analysis of how OXTR circuits shape social function in both health and disease.