Genome-wide profilings of transcriptome and translatome in mouse hippocampi after contextual fear conditioning

Memory stabilization after learning requires transcriptional and translational regulations in the brain, yet the temporal molecular changes following learning have not been explored at the genomic scale. We here employed ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in mouse hippocampus following contextual fear conditioning. We identified 104 genes that are dynamically regulated. Intriguingly, our analysis revealed novel repressive regulations in the hippocampus: translational suppression of ribosomal protein-coding genes at basal state; learning-induced early translational repression of specific genes; and late persistent suppression of a subset of genes via inhibition of ESR1/ERa signaling. Further behavioral analyses revealed that Nrsn1, one of the newly identified genes undergoing rapid translational repression, can act as a memory suppressor gene. This study unveils the yet unappreciated importance of gene repression mechanisms in memory formation. Overall design: The application of ribosome profiling and RNA-seq techniques to mouse hippocampi tissues after contextual fear conditioning and to mouse hippocampal primary cultures. Mouse ESCs were also examined.

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Cho J, Yu NK, Choi JH, Sim SE, Kang SJ, Kwak C, Lee SW, Kim JI, Choi DI, Kim VN, Kaang BK