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Sex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex

Authors: Jennifer Isaac, Sonia Karkare, Hymavathy Balasubramanian, Nicholas Schappaugh, Jarildy Javier, Maha Rashid, Malavika Murugan
Publication: bioRxiv
Date: March 10, 2023
Link to article: https://www.biorxiv.org/content/10.1101/2023.03.09.531947v1


The reinforcing nature of social interactions is necessary for the maintenance of appropriate social behavior. However, the neural substrates underlying social reward and whether these are shared with competing nonsocial rewarding stimuli remain unknown. We developed a fully automated, novel two choice (social-sucrose) operant assay in which mice choose between social and nonsocial rewards to allow for the direct comparison of reward-related behaviors associated with two competing stimuli. We performed cellular resolution calcium imaging of medial prefrontal cortex (mPFC) neurons in male and female mice across varying states of water restriction and social isolation. We found that mPFC neurons maintain largely non-overlapping, flexible representations of social and nonsocial reward that vary with internal state in a sex-dependent manner. Additionally, optogenetic manipulation of mPFC activity during the reward period of the assay disrupted reward-seeking behavior. Thus, using a novel operant assay, we have identified sex-dependent, non-overlapping neural representations of social and nonsocial reward in the mPFC that vary with internal state and that are essential for appropriate reward-seeking behavior.

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