Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories
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Tsai_Epigenetic Priming.pdf
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Author(s)
Joseph, Nadine F.
Horn, Meryl E.
Samiei, Alireza
Meng, Jia
Seo, Jinsoo
Rei, Damien
Bero, Adam W.
Phan, Trongha X.
Wagner, Florence
Holson, Edward
Date Issued
January 2014
Journal
Cell
Publisher
Elsevier
Citation
Graff, Johannes, Nadine F. Joseph, Meryl E. Horn, Alireza Samiei, Jia Meng, Jinsoo Seo, Damien Rei, et al. “Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories.” Cell 156, no. 1–2 (January 2014): 261–76.
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Author's final manuscript
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2013.12.020
