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Science. 2015 Oct 2;350(6256):82-7. doi: 10.1126/science.aac7368.

Multiple repressive mechanisms in the hippocampus during memory formation.

Author information

1
Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea. Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
2
Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
3
Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea. Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. narrykim@snu.ac.kr kaang@snu.ac.kr.
4
Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. narrykim@snu.ac.kr kaang@snu.ac.kr.

Abstract

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.

PMID:
26430118
DOI:
10.1126/science.aac7368
[Indexed for MEDLINE]
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