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Cell. 2014 Jan 16;156(1-2):261-76. doi: 10.1016/j.cell.2013.12.020.

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

Author information

1
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
2
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
5
Mallinckrodt Institute of Radiology, Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Center for Human Genetic Research, Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
7
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: lhtsai@mit.edu.

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.

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PMID:
24439381
PMCID:
PMC3986862
DOI:
10.1016/j.cell.2013.12.020
[Indexed for MEDLINE]
Free PMC Article

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