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lif-Lmetabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation ing or learning during memory reconsolidation (McKenzie and Eichenbaum, 2011; Nader and Hardt, 2009; Tronson and Taylor, 2007), several other studies have referred to pharmacologicalmight constitute a treatment option for remote traumata. means in order to enhance this process (Kaplan and Moore, 2011). Among those, histone deacetylase inhibitors (HDACis)SUMMARY Traumatic events generate some of the most enduring forms of memories. Despite the ele-vated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term trau-matic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) trau-mata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, suc-cessful 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 hippo-campal neuroplasticity mediated, in part, by S-nitro-sylation 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 epige-netically primes the expression of neuroplasticity-related genes, which is accompanied by highe