Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction and maternal behavior. Recent studies have tagged oxytocin as a ?trust? hormone, promising 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 a 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. Oxytocin action in maternal brain is especially important as it represents the most ancient and important function of oxytocin under a social context. To these ends, the proposed Brain Initiative Project in NYU School of Medicine on ?Oxytocin Modulation of Neural Circuit Function and Behavior? consists of four inter-related Projects and four Core facilities, including an Administrative Core, a Data Science Core, a Behavioral Optogenetics Core, and an Oxytocin Receptor Antibody Production Core. The overarching goal of the four Projects and the Cores is to achieve a better understanding of the oxytocin modulation in socio-spatial behaviors, 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) From the source, Project 1 and 2 will address the connectivity, behavioral influence, in vivo responses, release and experience- dependent changes of the oxytocin neurons. From the receiving ends, Project 3 will dive into detailed cellular, synaptic and microcircuit mechanisms that mediate the oxytocin actions. Lastly, Project 4 will combine the knowledge and techniques developed from Projects 1, 2, and 3 to investigate the state-dependent oxytocin modulation of aggressive behaviors at a brain site essential for aggression, the ventrolateral part of the ventromedial hypothalamus (VMHvl). Intriguingly, a group of oxytocin neurons are found neighboring the VMHvl, potentially providing a local source of oxytocin although its behavioral relevance is currently unknown. Together these Projects and Cores develop new tools, use cutting-edge techniques, and large-scale methods to provide an in-depth description of the neural circuitry for maternal socio-spatial behavior.

Public Health Relevance

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 maternal behavior and cognitive function.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZNS1)
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Gnadt, James W
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New York University
Schools of Medicine
New York
United States
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Eyring, Katherine W; Tsien, Richard W (2018) Direct Visualization of Wide Fusion-Fission Pores and Their Highly Varied Dynamics. Cell 173:819-821