Project Summary Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction, maternal care, and social behavior, as well as various ‘non-social’ aspects of internal state and physiological processes. Although sometimes referred to as a ‘trust’ hormone, a growing body of evidence across species and brain areas indicates that oxytocin can increase social salience, i.e., amplifying or enabling selective attention towards certain social stimuli, such as the sound of a crying infant or the presence of a threatening or high-status individual. Oxytocin is believed to have therapeutic potential, and delivery of oxytocin into the central nervous system promises to improve social deficits in various mental disorders, such as autism. Despite the enthusiasm for oxytocin, contradictory results in the efficacy of oxytocin in improving human social behaviors have been reported. Such inconsistency in literature is likely due to our poor understanding of complexity of oxytocin action, which likely varies with behavioral state, experience and brain structures. We believe that a better understanding of the endogenous action of oxytocin is the key to unleash the therapeutic potential of this highly evolutionary conserved neuropeptide. Advancing our understanding requires cross-level and comparative inter-disciplinary studies by an group of investigators with overlapping interests and the technical capability to analyze oxytocin signaling across molecular, physiological, systems behavioral and levels. This includes multi-animal interactions, as many mental disorders are impactful on social behavior, over the lifespan and throughout the brain. To these ends, this proposed U19 at NYU Grossman School of Medicine on “Oxytocin Modulation of Neural Circuit Function and Behavior” consists of four inter-related Projects and five Core facilities, designated by their responsibilities as Administrative, Behavior, Computational Modeling, Data Science, and Molecular Tools Cores. The overarching goal of the four Projects and Cores is to achieve a better understanding of the oxytocin modulation in socio-spatial behaviors through the development of new tools and theories, which we define as social interactions within a specific context or behavioral environment. Our team will join forces to tackle the oxytocin system from both the source (oxytocin neurons) and the receiving ends (oxytocin receptor-expressing neurons). For Overall Aim 1, Projects 1 and 2 ask how different populations of oxytocin neurons promote stable adult social hierarchy, extending to collective parenting to ensure the survival of offspring as one key advantage of a stable social ecosystem. For Overall Aim 2, Project 3 dives into detailed cellular, synaptic and microcircuit mechanisms that mediate the oxytocin actions. In Overall Aim 3, Project 4 combines knowledge and techniques developed from Projects 1, 2, and 3 to develop methods for specific circuit perturbations to affect socio-spatial learning over multiple spatio-temporal scales. Overall Aim 4 is to ensure that the students, postdocs, and staff team members receive good mentoring and conduct these studies in a supportive pro-social environment.

Public Health Relevance Statement Mental health disorders often involve disruptions of neuromodulatory systems. While oxytocin signaling has been implicated in autism, schizophrenia and other brain disorders, we know little about where and when oxytocin is released within the brain, or how it affects the circuits that regulate socio-spatial behaviors. Here, we take a multidisciplinary team approach to the synaptic, neuronal and circuit effects of oxytocin and the fundamental mechanisms by which this modulator affects parental care, adult social behavior, and cognitive function.