Memory is the capacity of an organism to acquire, store and recover information based on experience. In the brain, experiences that become memories appear as enduring changes only in a small set of activated neurons, called engrams.While the mechanisms of how such memories are deposited in engrams for short periods of time has received considerable attention over the past decade, the current knowledge of how memories are stored in engram cells in the long run is still scarce. Consequently, this project aims to identify the mechanisms based on which a memory becomes remote by integrating a wide range of analyses, from morphological to biochemical and molecular aspects of engram cells.We perform contextual fear conditioning on a TRAP2 mouse model, which enables to obtain an activity-dependent genetic labeling specifically of engram cells. For morphological changes, we analyze dendritic spines and synapses using confocal and transmission electron microscopy, respectively. For biochemical changes, we will characterize histones post-translational modification with mass spectrometry, and for molecular changes, we focus on transcriptional and epigenomic signatures with single-nuclei RNA-seq coupled with ATAC-seq and/or CUT&Tag.Since previous studies that have indicated that memory storage cannot reside solely at the level of dendritic spines and synapses, whose turnover is too fast to account for the stability of remote memories, and since epigenetic mechanisms can stably register experience-dependent cellular activity states for example in development, we hypothesize that epigenetic mechanisms might provide a nucleus-based solution of lasting enough nature to explain the basis of long-term memories.