Social Isolation Induces Rac1-Dependent Forgetting of Social Memory

Social isolation (SI) has detrimental effects on human and animal cognitive functions. In particular, acute isolation in adult mice impairs social recognition memory (SRM). Previous accounts of this impairment have focused primarily on memory consolidation. However, the current study suggests that impaired SRM results from enhanced forgetting. SI accelerates SRM decay without affecting memory formation. The impairment is caused by elevated Rac1 activity in the hippocampus. Using adeno-associated-virus-based genetic manipulation, we found that inhibition of Rac1 activity blocked forgetting of SRM in isolated adult mice, whereas activation of Rac1 accelerated forgetting in group-housed mice. Moreover, resocialization reversed the accelerated forgetting following isolation in correlation with suppression of Rac1 activity. In addition, accelerated long-term potentiation (LTP) decay in isolated mice brain slices was rescued by inhibition of Rac1 activity. Taken together, the findings lead us to conclude that social memory deficits in isolated mice are mediated by enhanced Rac1-dependent forgetting.