Systems consolidation reorganizes hippocampal engram circuitry - Source data

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 novel, but related situations (i.e., 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 suggest that systems consolidation models require updating to account for within-hippocampus reorganization that leads to qualitative shifts in memory precision.

Description of the data structure

File: Ko_et_al_Nature_2025.xlsx

Description: Microsoft Excel file containing all source data presented in the four main figures and ten extended data figures of the manuscript. Each tab corresponds to a specific figure, as indicated.