| Literature DB >> 28346453 |
Xinlu Ding1,2,3, Sanxiong Liu1,2,3, Miaomiao Tian1,2,3, Wenhao Zhang1, Tao Zhu1,2,3, Dongdong Li1,2,3, Jiawei Wu1, HaiTeng Deng1, Yichang Jia4, Wei Xie1, Hong Xie1,2,3,4, Ji-Song Guan1,2,3.
Abstract
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 p66α 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.Entities:
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Year: 2017 PMID： 28346453 DOI： 10.1038/nn.4536
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884