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

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

doi:10.1016/j.cell.2013.12.020

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

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

Department of Brain Sciences

Research output: Contribution to journal › Article › peer-review

307 Scopus citations

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	https://doi.org/10.1016/j.cell.2013.12.020
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.

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Gräff, J., Joseph, N. F., Horn, M. E., Samiei, A., Meng, J., Seo, J., Rei, D., Bero, A. W., Phan, T. X., Wagner, F., Holson, E., Xu, J., Sun, J., Neve, R. L., Mach, R. H., Haggarty, S. J., & Tsai, L. H. (2014). Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories. Cell, 156(1-2), 261-276. https://doi.org/10.1016/j.cell.2013.12.020

@article{a078eb41ebd643fa9d11b07b680f96fb,

title = "Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories",

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.",

author = "Johannes Gr{\"a}ff and Joseph, \{Nadine F.\} and Horn, \{Meryl E.\} and Alireza Samiei and Jia Meng and Jinsoo Seo and Damien Rei and Bero, \{Adam W.\} and Phan, \{Trongha X.\} and Florence Wagner and Edward Holson and Jinbin Xu and Jianjun Sun and Neve, \{Rachael L.\} and Mach, \{Robert H.\} and Haggarty, \{Stephen J.\} and Tsai, \{Li Huei\}",

note = "Funding Information: We thank MIT{\textquoteright}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. ",

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doi = "10.1016/j.cell.2013.12.020",

language = "English",

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journal = "Cell",

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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.

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JF - Cell

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ER -

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

Abstract

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