Engram-specific transcriptome profiling of contextual memory consolidation.

Rao-Ruiz, Priyanka; Couey, Jonathan J; Marcelo, Ivo M; Bouwkamp, Christian G; Slump, Denise E; Matos, Mariana R; van der Loo, Rolinka J; Martins, Gabriela J et al. · Nat Commun · 2019

basic_science · Level V

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Abstract

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<sup>-13</sup>), including Atf3 (P = 2.4 × 10<sup>-41</sup>), Penk (P = 1.3 × 10<sup>-15</sup>), and Kcnq3 (P = 3.1 × 10<sup>-12</sup>). 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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