| First Author | Ding X | Year | 2017 |
| Journal | Nat Neurosci | Volume | 20 |
| Issue | 5 | Pages | 690-699 |
| PubMed ID | 28346453 | Mgi Jnum | J:243994 |
| Mgi Id | MGI:5912773 | Doi | 10.1038/nn.4536 |
| Citation | Ding X, et al. (2017) Activity-induced histone modifications govern Neurexin-1 mRNA splicing and memory preservation. Nat Neurosci 20(5):690-699 |
| abstractText | 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 p66alpha 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. |
