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

Johannes Gräff, Nadine F. Joseph, Meryl E. Horn, Alireza Samiei, Jia Meng, Jinsoo Seo, Damien Rei, Adam W. Bero, Trongha X. Phan, Florence Wagner, Edward Holson, Jinbin Xu, Jianjun Sun, Rachael L. Neve, Robert H. Mach, Stephen J. Haggarty, Li Huei Tsai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)261-276
Number of pages16
JournalCell
Volume156
Issue number1-2
DOIs
StatePublished - Jan 27 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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