Behavioral evidence across species suggests that oxytocin plays a general role in many aspects of social cognition, yet the neurobiological substrates through which it acts at the neural circuit level are not fully understood. An intriguing but untested idea is that centrally released oxytocin acting on limbic brain regions allows for the neural processing of social cues to gate activity in areas involved in seeking reward, thus facilitating the motivation to socially interact and the reinforcement of conspecific cues. Our long-term goal is to elucidate how oxytocin modulates the oxytocin receptor rich regions underlying social information processing and reward to enhance social cognition. The objective here is to record from chronic electrode implants within these regions during social behavioral paradigms in rodents. Our central hypothesis is that the motivation to interact socially is determined by a balance between positive and negative valence cues, and that oxytocin acts to enhance how positive valence cues and/or suppress how negative valence cues modulate the functional neural connections between cue and reward processing areas, helping to reinforce their encoding. The rationale for our proposal is that, once we know how oxytocin affects functional connectivity between these areas in natural social contexts, our improved knowledge about oxytocin's sites of action will enable direct manipulation of these circuits to enhance prosocial behavior. Two complementary specific aims in two different rodent models will be pursued, each chosen to maximize our ability to deduce the electrophysiological effects of either oxytocin loss of function (Aim 1) or gain of function (Aim 2) during social interactions. Our proposal's significance lies in the fact that it will implicate a specific central limbic circuit in mediating oxytocin's role in facilitating social motivation and socially reinforced learning. The combination of in vivo electrophysiology with oxytocin manipulation in freely moving, socially interacting rodents is an innovation that will enable key questions to be addressed about how real-time neural activity within limbic circuits is dynamically modulated by oxytocin in natural social interactions.
The proposed research is relevant to public health because intranasal oxytocin is now in clinical trials as a treatment for ameliorating social dysfunctions in several mental health disorders, even though our understanding of how oxytocin works in the brain to promote social cognition is not yet fully elucidated. Thus, this research will elucidate basic mechanisms to help enable better treatments for social deficits.
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