REM sleep-active hypothalamic neurons may contribute to hippocampal social-memory consolidation

The hippocampal CA2 region plays a key role in social memory. The encoding of such memory involves afferent activity from the hypothalamic supramammillary nucleus (SuM) to CA2. However, the neuronal circuits required for consolidation of freshly encoded social memory remain unknown. Here, we used circuit-specific optical and single-cell electrophysiological recordings in mice to explore the role of sleep in social memory consolidation and its underlying circuit mechanism. We found that SuM neurons projecting to CA2 were highly active during rapid-eye-movement (REM) sleep but not during non-REM sleep or quiet wakefulness. REM-sleep-selective optogenetic silencing of these neurons impaired social memory. By contrast, the silencing of another group of REM sleep-active SuM neurons that projects to the dentate gyrus had no effect on social memory. Therefore, we provide causal evidence that the REM sleep-active hypothalamic neurons that project to CA2 are specifically required for the consolidation of social memory. [Display omitted] •Both SuM-CA2- and SuM-DG-projecting neurons are highly active during REM sleep•REM-sleep-selective silencing of SuMCA2 neurons impairs social memory•REM-sleep-selective silencing of SuMDG neurons impairs spatial but not social memory•CA2SuM-recipient neurons are highly active during REM sleep Qin et al. identify two groups of REM sleep-active supramammillary neurons, one projecting to the hippocampal CA2 and the other to the dentate gyrus. They find that these two cell groups critically contribute to REM-sleep-associated consolidation of social and spatial memories, respectively.