Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24 h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P = 6.2 × 10−13), including Atf3 (P = 2.4 × 10−41), Penk (P = 1.3 × 10−15), and Kcnq3 (P = 3.1 × 10−12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory.

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Journal Nature Communications
Rao-Ruiz, P, Couey, J.J., Marcelo, IM, Bouwkamp, C.G, van der Zee, R, Matos, M.R., … Kushner, S.A. (2019). Engram-specific transcriptome profiling of contextual memory consolidation. Nature Communications, 10. doi:10.1038/s41467-019-09960-x