CA1 Engram Cell Dynamics Before and After Learning.

A fundamental question in neuroscience is how memory formation shapes brain activity at the level of neuronal populations. Recent studies of hippocampal 'engram' cells-neurons identified by learning-induced immediate early gene (IEG) expression-propose that these populations form the cellular substrate for memory. Previous experimental work suggests that cells are recruited into engrams via elevated intrinsic excitability and that learning drives coactivity among these cells to support retrieval. Despite this, an understanding of how engram dynamics evolve across learning and recall remains incomplete. Here, we combined activity-dependent genetic tagging with longitudinal two-photon calcium imaging to track CA1 engram population dynamics before and after fear conditioning. Our results reveal that engram activity is modulated by intrinsic dynamics, behavioral state, and stimulus-cued reactivation. Consistent with the idea that intrinsic dynamics bias engram allocation, spontaneous activity during rest predicted future engram membership-up to two days prior to