期刊
NATURE NEUROSCIENCE
卷 20, 期 5, 页码 690-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4536
关键词
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资金
- National Basic Research Program of China [2013CB835100]
- NSFC [31671104, 31371059]
- Brain Inspired Computing Research, Tsinghua University [20141080934]
- Beijing Municipal Science & Technology Commission [Z161100000216126]
- Beijing NOVA program [2015B057]
- National Natural Science Foundation of China
- German Research Foundation (DFG) [NSFC (61621136008)/DGF TRR-169]
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process. Activity-dependent phosphorylation of p66a via AMP-activated protein kinase recruits HDAC2 and Suv39h1 to establish repressive histone markers and changes the connectivity of the activated neurons. Removal of Suv39h1 abolished the activity-dependent shift in Nrxn1 splice isoform choice and reduced the stability of established memories. We uncover a cell-autonomous process for memory preservation in which memory-related neurons initiate a late-onset reduction of their rewiring capacities through activity-induced histone modifications.
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