Systems consolidation reorganizes hippocampal engram circuitry

Sangyoon Y. Ko, Yiming Rong, Adam I. Ramsaran, Xiaoyu Chen, Asim J. Rashid, Andrew J. Mocle, Jagroop Dhaliwal, Ankit Awasthi, Axel Guskjolen, Sheena A. Josselyn and Paul W. Frankland ()
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Sangyoon Y. Ko: The Hospital for Sick Children
Yiming Rong: The Hospital for Sick Children
Adam I. Ramsaran: The Hospital for Sick Children
Xiaoyu Chen: The Hospital for Sick Children
Asim J. Rashid: The Hospital for Sick Children
Andrew J. Mocle: The Hospital for Sick Children
Jagroop Dhaliwal: The Hospital for Sick Children
Ankit Awasthi: The Hospital for Sick Children
Axel Guskjolen: The Hospital for Sick Children
Sheena A. Josselyn: The Hospital for Sick Children
Paul W. Frankland: The Hospital for Sick Children

Nature, 2025, vol. 643, issue 8072, 735-743

Abstract: Abstract Episodic memories—high-fidelity memories for events that depend initially on the hippocampus—do not maintain their precision in perpetuity. One benefit of this time-dependent loss of precision is the emergence of event-linked gist memories that may be used to guide future behaviour in new but related situations (that is, generalization)1–3. Models of systems consolidation propose that memory reorganization accompanies this loss of memory precision1,4; however, the locus of this reorganization is unclear. Here we report that time-dependent reorganization of hippocampal engram circuitry is sufficient to explain shifts in memory precision associated with systems consolidation. Using engram labelling tools in mice, we demonstrate that the passage of time rewires hippocampal engram circuits, enabling hippocampal engram neurons to be promiscuously active and guide behaviour in related situations that do not match the original training conditions. Reorganization depends on hippocampal neurogenesis; eliminating hippocampal neurogenesis prevents reorganization and maintains precise, event memories. Conversely, promoting hippocampal neurogenesis accelerates memory reorganization and the emergence of event-linked gist memories in the hippocampus. Our results indicate that systems consolidation models require updating to account for within-hippocampus reorganization that leads to qualitative shifts in memory precision.

Date: 2025
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DOI: 10.1038/s41586-025-08993-1

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