Details

Autor(en) / Beteiligte

• Gräff, Johannes
• Joseph, Nadine F.
• Horn, Meryl E.
• Samiei, Alireza
• Meng, Jia
• Seo, Jinsoo
• Rei, Damien
• Bero, Adam W.
• Phan, Trongha X.
• Wagner, Florence
• Holson, Edward
• Xu, Jinbin
• Sun, Jianjun
• Neve, Rachael L.
• Mach, Robert H.
• Haggarty, Stephen J.
• Tsai, Li-Huei

Titel

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

Ist Teil von

• Cell, 2014-01, Vol.156 (1-2), p.261-276

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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. [Display omitted] •Remote fear memories cannot be attenuated by conventional reconsolidation methods•Recalling remote memories fails to induce histone acetylation-mediated plasticity•HDAC inhibitors reinstate metabolic activity and synaptic and structural plasticity•Applying HDAC inhibitors during reconsolidation stably attenuates remote fears An HDAC2 inhibitor reinstates synaptic and structural plasticity to stably attenuate remote fear-associated memories.