Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Association Learning / drug effects
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Association Learning / physiology
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Base Sequence
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Calcineurin / genetics
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Calcineurin / metabolism
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Cerebral Cortex / drug effects
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Cerebral Cortex / physiology*
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Conditioning, Classical / drug effects
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Conditioning, Classical / physiology
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CpG Islands / genetics
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DNA Methylation* / drug effects
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Early Growth Response Protein 1 / genetics
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Early Growth Response Protein 1 / metabolism
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Electroshock
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Fear
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Male
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Memory / drug effects
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Memory / physiology*
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Molecular Sequence Data
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / physiology
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / metabolism
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Time Factors
Substances
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Early Growth Response Protein 1
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RNA, Messenger
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Receptors, N-Methyl-D-Aspartate
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Calcineurin