PT - JOURNAL ARTICLE AU - Isaac, Jennifer AU - Karkare, Sonia AU - Balasubramanian, Hymavathy AU - Schappaugh, Nicholas AU - Javier, Jarildy AU - Rashid, Maha AU - Murugan, Malavika TI - Sex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex AID - 10.1101/2023.03.09.531947 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.03.09.531947 4099 - http://biorxiv.org/content/early/2023/03/14/2023.03.09.531947.short 4100 - http://biorxiv.org/content/early/2023/03/14/2023.03.09.531947.full AB - The reinforcing nature of social interactions is necessary for the maintenance of appropriate social behavior. However, the neural substrates underlying social reward processing remain unknown. It is also unclear whether these neural substrates are shared with those involved in nonsocial rewarding processing. We developed a fully automated, novel two choice (social-sucrose) operant assay in which mice choose between social and nonsocial rewards to directly compare the 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.Competing Interest StatementThe authors have declared no competing interest.