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

292 Citations (Scopus)


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
Pages (from-to)261-276
Number of pages16
Issue number1-2
Publication statusPublished - 2014
Externally publishedYes

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