Oxytocin Modulation of Social Behavior

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The goal of this proposal is to dissect the underlying mechanisms and relationships of oxytocin release in the mouse brain as involved in various social behaviors. Oxytocin is an evolutionarily conserved neuropeptide associated with various social behaviors essential for life, such as social interaction, parental care, reproduction, defense, and more. An emerging view in the field is that disruptions in oxytocin signaling may be involved in disorders of social behavior, social cognition, and parental care (including child neglect or postpartum depression). However, it is unclear how, when, or where oxytocin is released in the brain to enact on specific neural circuits to enable social behavior. Therefore. It is essential to delineate the physiological role of oxytocin in the context of social behavior. The overall hypothesis is that oxytocin is rarely released, but episodes of phasic release predict sudden changes in social behavior, in a manner consistent with enhancing the salience of social (audible) cues. To test this fundamental question, I will first carry out (Aim 1) behavioral studies to identify the most robust social behavior phenotypes in mice that are sensitive to oxytocin regulation (activation and suppression). Then (Aim 2) I will develop and validate a synthetic nanosensor for real-time optical tracking of oxytocin in vivo. Lastly, (Aim 3) I will use the oxytocin nanosensor to follow in real-time oxytocin release and distribution during the behaviors identified in Aim 1, as well as employ fiber photometry and electrophysiology to measure the cortical and oxytocin neuron firing patterns associated with these behaviors. Innovation: The development of the oxytocin nanosensor will be a highly useful tool likely to be used by many as well as can serve as a basis for diagnostic measurement if oxytocin in the clinic. Taken together, the experiments to be performed in this proposal will provide valuable insight on the release and action of oxytocin in the brain and the related neural networks during social behavior.