Scientific Publications

Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories.

Publication TypeJournal Article
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, and Tsai LH
AbstractTraumatic 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.
Year of Publication2014
JournalCell
Volume156
Issue1-2
Pages261-76
Date Published (YYYY/MM/DD)2014/01/16
ISSN Number0092-8674
DOI10.1016/j.cell.2013.12.020
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24439381?dopt=Abstract