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 language | English |
|---|---|
| Pages (from-to) | 261-276 |
| Number of pages | 16 |
| Journal | Cell |
| Volume | 156 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - 2014 |
Bibliographical note
Funding Information:We thank MIT’s BioMicroCenter for the RNA sequencing, Martin Kahn for help with the qRT-PCR and IHC experiments, and Theo Elfers for critical comments on the manuscript. This work was partially supported by NIH NINDS/NIA (NS078839) to L.-H.T. and NIH/NIDA (R01DA028301) to S.J.H., the Picower Neurological Disorder Fund (PNDRF), the Stanley Medical Foundation, HHMI, and a Bard Richmond fellowship to J.G.