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.