Restoring access to long-term social recognition memories disrupted by sleep deprivation.

Long-term social memories are vital for forming and maintaining relationships, and social amnesia can disrupt daily life. Using a new paradigm to study these hippocampus-dependent memories, we show that mice can distinguish between multiple social experiences even when they occur in the same context across days. Sleep deprivation immediately after socialization disrupts memory consolidation, leading to social amnesia. Treatment with the Food and Drug Administration-approved phosphodiesterase type 4 inhibitor roflumilast during sleep deprivation protects memory consolidation, while administration immediately before testing reverses social amnesia temporarily. Optogenetic reactivation of dentate gyrus engram cells restores social memory access and enables selective retrieval of individual memories. In addition, using two cFos-based engram-tagging strategies, we find that sleep deprivation selectively affects reactivation of experience-specific engrams while not affecting engram formation or overlap. These results suggest that impaired engram reactivation contributes to sleep deprivation-induced social amnesia and highlights the role of the hippocampal dentate gyrus in maintaining and distinguishing social experiences in a single context.