Systems consolidation reorganizes hippocampal engram circuitry

• 成果类型: Article
• 署名作者: Ko, Sangyoon Y.; Rong, Yiming; Ramsaran, Adam I.; Chen, Xiaoyu; Rashid, Asim J.; Mocle, Andrew J.; Dhaliwal, Jagroop; Awasthi, Ankit; Guskjolen, Axel; Josselyn, Sheena A.; Frankland, Paul W.
• 署名单位: University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; University of Toronto; University of Toronto; Canadian Institute for Advanced Research (CIFAR)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3498
• DOI: 10.1038/s41586-025-08993-1
• 发表日期: 2025-07-17
• 关键词: episodic memory; retrograde-amnesia; cell-proliferation; generated neurons; adult; neurogenesis; born; context; period; MODEL

摘要

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, 2-3. 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.