TY - JOUR
T1 - Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories
AU - Gräff, Johannes
AU - Joseph, Nadine F.
AU - Horn, Meryl E.
AU - Samiei, Alireza
AU - Meng, Jia
AU - Seo, Jinsoo
AU - Rei, Damien
AU - Bero, Adam W.
AU - Phan, Trongha X.
AU - Wagner, Florence
AU - Holson, Edward
AU - Xu, Jinbin
AU - Sun, Jianjun
AU - Neve, Rachael L.
AU - Mach, Robert H.
AU - Haggarty, Stephen J.
AU - Tsai, Li Huei
N1 - 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.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84892776254&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2013.12.020
DO - 10.1016/j.cell.2013.12.020
M3 - Article
C2 - 24439381
AN - SCOPUS:84892776254
SN - 0092-8674
VL - 156
SP - 261
EP - 276
JO - Cell
JF - Cell
IS - 1-2
ER -