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Artificial hibernation uncovers distinct synaptic engram architecture for memory retention

Lin, Y.-J.; Takahashi-Nakazato, A.; Tsutsumi, K.; Takahashi, T.; Mercier, D.; Ashitomi, H.; Chiang, M.-C.; Haberl, M.; Uytiepo, M.; Maximov, A.; Makino, Y.; Nemoto, T.; Enoki, R.; Hirano, A.; Soga, K.; Looprasertkul, S.; Ohno, N.; Kubota, Y.; Sakurai, T.; Tanaka, K. Z.

2025-12-11 neuroscience
10.64898/2025.12.09.692927 bioRxiv
Show abstract

The memory trace at the neuronal and synaptic levels remains controversial. Stable, larger spines are thought to support memory, but the high turnover of dendritic spines and the drifting of neuronal representations following memory formation suggest alternative possibilities. To elucidate a structural trace underlying memory retention, we utilize a mouse model of artificial hibernation. During hibernation, hippocampal neurons exhibited a substantial reduction in their activity and an extensive elimination of dendritic spines and synapses. Despite these changes, their memory and associated hippocampal neuronal representations are intact after arousal. We find that a subset of spines is maintained during hibernation. These spatially clustered engram-engram synapses are exclusively protected from elimination and characterized by synaptic contacts with multi-synaptic boutons. These findings suggest that synaptic engram architecture, rather than larger spines per se, is resilient to network remodeling and underlies long-term memory retention.

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