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bioRxiv · 10.64898/2026.01.13.699230

A hypothalamo-septo-hippocampal circuit for REM sleep-dependent consolidation of social memory

Qin, H.·Jian, T.·Jin, W.·Liang, M.·Liao, X.·Zhang, K.·Liang, S.·Zhang, C.·He, C.·Jia, H.·Wang, Y.·Han, J.·Chen, X.
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Abstract

REM sleep constitutes a critical window for memory consolidation, yet the brain circuits orchestrating this process remain incompletely defined. Here, we identify a lateral supramammillary nucleus (SuM)-medial septum (MS) projection as a REM sleep-specialized pathway essential for hippocampal memory consolidation. Fiber photometry and optrode recordings revealed that lateral SuM-MS projecting neurons were selectively active during REM sleep. REM-specific optogenetic silencing of this projection impaired consolidation of both social and contextual fear memories. Crucially, silencing of its downstream target, the MS-CA2 pathway, during REM sleep selectively disrupted social memory while sparing contextual fear memory. This functional dissection establishes a hypothalamo-septo-hippocampal circuit (lateral SuM-MS-CA2) dedicated to social memory processing, in parallel to the recently-described direct SuM-CA2 pathway. These results also position the SuM as a REM sleep-hub that routes information via parallel septal pathways to consolidate distinct memory modalities.

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Qin, H., Jian, T., Jin, W., Liang, M., Liao, X., Zhang, K., Liang, S., Zhang, C., He, C., Jia, H., Wang, Y., Han, J., Chen, X.. 2026-01-13. A hypothalamo-septo-hippocampal circuit for REM sleep-dependent consolidation of social memory. https://doi.org/10.64898/2026.01.13.699230

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