Project Summary/Abstract Affiliative social interactions play an essential role in the reproduction and survival of social species including humans. Its disruption in neuropsychiatric conditions or during times of social isolation such as the COVID-19 pandemic can take a heavy toll on mental and physical well-being. However, the neural circuit mechanisms governing affiliative social behaviors are not well understood. 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. However, the neural circuitry underlying allogrooming has been sparsely explored and few brain areas that encode and promote affiliative allogrooming have been identified. Deciphering the neural circuit mechanisms of affiliative allogrooming will provide key insights into the neural basis underlying social affiliation and attachment. Given the prominent impairment in affiliative social behavior in several neuropsychiatric disorders, including autism and schizophrenia, this understanding can guide circuit-level investigation of disease mechanisms and development of interventions. In recent studies, we established an ethologically relevant and experimentally tractable paradigm for studying allogrooming behavior in laboratory mice and uncovered a key role of a medial amygdala (MeA)-to-medial preoptic area (MPOA) circuit in controlling this behavior. These findings open up valuable opportunities for in-depth dissection of the functional circuitry underlying allogrooming behavior. The central objective of this application is to elucidate the neural circuit mechanisms through which the MPOA controls allogrooming, which represents a critical next step toward defining the functional organization of the neural circuitry of affiliative social behavior. We propose a series of experiments to comprehensively probe whether and how the activity of select MPOA neuronal subpopulations and their downstream targets regulate allogrooming behavior. Specifically, we will address the following important questions: (Aim 1) Is allogrooming behavior controlled by select, molecularly defined MPOA subpopulations? (Aim 2) Whether and how neural activity dynamics in MPOA neurons encodes social sensory cues and allogrooming behavior? (Aim 3) What are the neural circuits downstream of the MPOA that mediate allogrooming behavior? Our proposed research will integrate state-of-the-art techniques for functional manipulation of specific neuronal subpopulations, in vivo imaging of neuronal activity dynamics in awake, freely behaving animals, and functional mapping of neural projections to reveal how specific MPOA neuronal subpopulations respond to conspecific cues and control the display of allogrooming through their downstream projections. This investigation will yi...