Rac1 in parvalbumin neurons of the medial prefrontal cortex governs rapid forgetting of social memory.

Social memory can undergo rapid forgetting at first according to the Ebbinghaus forgetting curve, for which the underlying mechanism remains entirely unknown. Here, we reported that rapid forgetting of social memory did not occur as indicated by social preference on stranger 2 (S2) over stranger 1 (S1) mouse, tested shortly after social interaction with S1. However, rapid forgetting of both social and object memories occurred as indicated by no social or object preference, respectively, when the constitutive active (CA) variant of Rac1 was knocked-in parvalbumin (PV) but not somatostatin (SST) neurons of the brain. Furthermore, rapid forgetting of only social memory occurred if this CA variant was knocked-in PV but not SST neurons of the medial prefrontal cortex (mPFC). By contrast, rapid forgetting of social memory was prevented by the dominant negative (DN) variant of Rac1 knocked-in PV neurons of the mPFC. Moreover, fiber photometry revealed that PV but not SST neurons of the mPFC generated dual calcium peaks to delineate each social interaction event. Thus, PV-specific Rac1 activity of the mPFC is both necessary and sufficient for controlling social behavior via rapid forgetting of social memory, providing a novel understanding of social behaviors under health and disease conditions.