Wednesday, February 5, 2025
2/5/2025
PROJECT SUMMARY Most mammals, including humans, navigate a life motivated and shaped by a drive to seek rewards such as food, water, and social interactions. Social stimuli can act as positive reinforcers, driving animals to pursue and interact with other members of their own species (e.g., people regularly hanging out with friends or a mouse repeatedly visiting to investigate a novel conspecific). Significantly, deficits in motivation to seek socially rewarding stimuli and deficits in social reward processing are associated with several disorders, such as Autism Spectrum Disorders. While the neural substrates underlying non-social reward-related behaviors (e.g., food rewards) have been studied extensively, similar studies have been more difficult for social rewards because of the inherent complexity of social interactions. It is unclear if there are differences in how the brain processes social versus non-social rewards. Additionally, although intranasal oxytocin delivery alleviates social motivation deficits in human subjects with autism, how oxytocin modulates neural circuits mediating social reward-related behaviors remains poorly understood. Therefore, addressing these questions will have immense consequences for human health. We hope to address these gaps in knowledge by combining cellular resolution imaging techniques and optogenetics with a novel operant behavioral paradigm to thoroughly and systematically map how social and non-social rewards are represented in the medial prefrontal cortex (AIM 1a). We will determine if the mPFC reward representations are modulated by the internal state of the animal. (AIM 1b). We will evaluate how oxytocin inputs modulate social and non-social reward representations in the mPFC by imaging the activity of mPFC neurons while silencing oxytocin inputs to the mPFC (AIM 2). Finally, we will determine if social reward representations such as proximity of social reward, valence, and reward prediction error are functionally clustered in mPFC projection populations (AIM 3). In summary, this research will help us identify differences and similarities in how the brain encodes social rewards versus non-social rewards and how the animal's internal state modulates these representations. Additionally, given the promising therapeutic possibility of using intranasal oxytocin administration to children and adults with autism, elucidation of the role of the oxytocin on mPFC function will be a valuable addition to the autism research community.
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