Multiple repressive mechanisms in the hippocampus during memory formation

Science  02 Oct 2015:
Vol. 350, Issue 6256, pp. 82-87
DOI: 10.1126/science.aac7368

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Memory consolidation by gene suppression

Storing a persistent memory in the brain involves dynamic gene regulation. However, our knowledge of the target genes controlled during memory formation is limited. Cho et al. used RNA sequencing and ribosome profiling to compare transcription and translational levels in the mouse hippocampus before and after memory formation. Under basal conditions, there was an unexpected translational repression of ribosomal protein-coding genes. Early after learning, specific genes were translationally repressed. Later, suppression of a group of genes resulted from the inhibition of estrogen receptor alpha signaling. Thus, suppression mechanisms in the hippocampus appear to play a major role during memory consolidation.

Science, this issue p. 82


Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERα) signaling. In behavioral analyses, overexpressing Nrsn1, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation.

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