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Cell DOI:10.1016/j.cell.2013.12.020

Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories.

Publication TypeJournal Article
Year of Publication2014
AuthorsGräff, J, Joseph, NF, Horn, ME, Samiei, A, Meng, J, Seo, J, Rei, D, Bero, AW, Phan, TX, Wagner, F, Holson, E, Xu, J, Sun, J, Neve, RL, Mach, RH, Haggarty, SJ, Tsai, L-H
Date Published2014 Jan 16
KeywordsAnimals, Epigenesis, Genetic, Fear, Hippocampus, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Male, Memory, Long-Term, Mice, Mice, Inbred C57BL, Neuronal Plasticity, Transcriptome

Traumatic events generate some of the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that, whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes, which is accompanied by higher metabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata.


Alternate JournalCell
PubMed ID24439381
PubMed Central IDPMC3986862
Grant ListR01DA028301 / DA / NIDA NIH HHS / United States
NS078839 / NS / NINDS NIH HHS / United States
R01 NS078839 / NS / NINDS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R01 DA028301 / DA / NIDA NIH HHS / United States