Deconstruction of a memory engram reveals distinct ensembles recruited at learning

Nature Neuroscience 2026
Clément Pouget, Flora Morier, Livia Autore, Nadja Treiber, Pablo Fernández García, Nina Mazza, Run Zhang, Isaiah L. Reeves, Stephen M. Winston, Mark A. Brimble, Christina K. Kim & Gisella Vetere

Abstract
The mechanisms of associative memory formation, including which cells encode a memory and the timing of their engagement, remain poorly understood. By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we identified nonoverlapping dorsal CA1 neuronal ensembles that are differentially active during associative fear memory acquisition. We dissected the acquisition experience into periods during which salient stimuli were presented, or certain mouse behaviors occurred, and found that cells associated with specific acquisition periods are sufficient alone to drive memory expression and contribute to fear engram formation. This study delineated the distinct identities of the cell ensembles active during learning and revealed which ones form the core engram and are essential for memory formation and recall.