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
Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada.
Temerty Centre for Artificial Intelligence Research and Education in Medicine, University of Toronto, Toronto, Ontario, Canada.
Nature. 2025 May 14. doi: 10.1038/s41586-025-08993-1.
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). Models of systems consolidation propose that memory reorganization accompanies this loss of memory precision; 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.
情景记忆——最初依赖海马体的对事件的高保真记忆——不会永远保持其精确性。这种随时间推移而丧失精确性的一个好处是出现了与事件相关的梗概记忆，这些梗概记忆可用于指导在新的但相关的情境中的未来行为（即泛化）。系统巩固模型提出，记忆重组伴随着这种记忆精确性的丧失；然而，这种重组的位点尚不清楚。在这里，我们报告海马体记忆印迹回路随时间的重组足以解释与系统巩固相关的记忆精确性的变化。利用小鼠中的记忆印迹标记工具，我们证明时间的推移会重塑海马体记忆印迹回路，使海马体记忆印迹神经元能够杂乱地活跃，并在与原始训练条件不匹配的相关情境中指导行为。重组依赖于海马体神经发生；消除海马体神经发生会阻止重组并维持精确的事件记忆。相反，促进海马体神经发生会加速记忆重组以及海马体中与事件相关的梗概记忆的出现。我们的结果表明，系统巩固模型需要更新，以考虑海马体内导致记忆精确性发生质的变化的重组。
