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Cortical DNA methylation maintains remote memory


A behavioral memory's lifetime represents multiple molecular lifetimes, suggesting the necessity for a self-perpetuating signal. One candidate is DNA methylation, a transcriptional repression mechanism that maintains cellular memory throughout development. We found that persistent, gene-specific cortical hypermethylation was induced in rats by a single, hippocampus-dependent associative learning experience and pharmacologic inhibition of methylation 1 month after learning disrupted remote memory. We propose that the adult brain utilizes DNA methylation to preserve long-lasting memories.

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Figure 1: Learning induces persistent DNA methylation of CaN in the prefrontal cortex.
Figure 2: Cortical DNA methylation persists for at least 30 d.
Figure 3: Cortical DNA methylation is required for remote memory.


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The authors would like to thank O.S. Ahmed for technical assistance and M. Han of the UAB Genomics Core Facility. This work was supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the National Institute on Drug Abuse, the American Health Assistance Foundation, the Evelyn F. McKnight Brain Research Foundation and Philip Morris.

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Authors and Affiliations



C.A.M. and J.D.S. conceived of the project. C.A.M., G.R. and J.D.S. designed the experiments. G.R. contributed to assay development. C.A.M., C.F.G., J.A.W., R.R.P., I.M.R., A.H., M.D.R. and C.R.Y. performed the experiments. C.A.M. wrote the manuscript. G.R. and J.D.S. edited the manuscript.

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Correspondence to Courtney A Miller or J David Sweatt.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5, Supplementary Tables 1–3 and Supplementary Methods (PDF 866 kb)

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Miller, C., Gavin, C., White, J. et al. Cortical DNA methylation maintains remote memory. Nat Neurosci 13, 664–666 (2010).

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