Engram-specific transcriptome profiling of contextual memory consolidation

Priyanka Rao-Ruiz, Jonathan J. Couey, Ivo M. Marcelo, Christian G. Bouwkamp, Denise E. Slump, Mariana R. Matos, Rolinka J. van der Loo, Gabriela J. Martins, Mirjam van den Hout, Wilfred F. van IJcken, Rui M. Costa, Michel C. van den Oever, Steven A. Kushner*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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 −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.

Original languageEnglish
Article number2232
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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