Hippocampal Memory Traces Are Differentially Modulated by Experience, Time, and Adult Neurogenesis

Memory traces are believed to be ensembles of cells used to store memories. To visualize memory traces, we created a transgenic line that allows for the comparison between cells activated during encoding and expression of a memory. Mice re-exposed to a fear-inducing context froze more and had a greater percentage of reactivated cells in the dentate gyrus (DG) and CA3 than mice exposed to a novel context. Over time, these differences disappeared, in keeping with the observation that memories become generalized. Optogenetically silencing DG or CA3 cells that were recruited during encoding of a fear-inducing context prevented expression of the corresponding memory. Mice with reduced neurogenesis displayed less contextual memory and less reactivation in CA3 but, surprisingly, normal reactivation in the DG. These studies suggest that distinct memory traces are located in the DG and in CA3 but that the strength of the memory is related to reactivation in CA3. [Display omitted] •The DG and CA3 contain memory traces for fear-inducing contexts•Over time, contextual memories generalize and become less localized in CA3•Optical inhibition of context-specific DG or CA3 cells inhibits memory expression•Ablating neurogenesis impairs memory traces in CA3, but not in the DG In this study, Denny et al. created the ArcCreERT2 mice to indelibly label a memory trace in the hippocampus and addressed how memory traces are influenced by experience, time, and adult hippocampal neurogenesis.