Dynamic methylation driven by neuronal activity in hippocampal neurons impacts complex behavior

Anita E. Autry, Megumi Adachi, Lisa M. Monteggia

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Epigenetic processes are well-known to play critical roles in learning and memory. Among epigenetic processes, accumulating data suggests that DNA methylation in particular is a critical determinant of learning and memory. In vitro data have suggested that DNA methyltransferase inhibitors can trigger DNA demethylation and subsequent gene expression of the brain-derived neurotrophic factor gene in an activity dependent manner. To examine if these processes occur in vivo, we chronically infused DNMT inhibitors into the hippocampus and examined the impact on behavior. We find that chronic DNMT inhibition in the hippocampus results in increased anxiety-related behavior and deficits in context-dependent fear conditioning accompanied by an increase in BDNF expression. Gene expression changes were blocked by pretreatment with the NMDA receptor antagonist AP5, suggesting that DNMT inhibition enhances gene expression in an activity-dependent manner and that, conversely, the behavior deficits and abnormal gene expression are facilitated by NMDA receptor activity.[Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)439-447
Number of pages9
JournalFrontiers in Biology
Issue number5
StatePublished - Sep 17 2015
Externally publishedYes


  • DNA methylation
  • NMDA receptors
  • behavior
  • hippocampus
  • learning and memory

ASJC Scopus subject areas

  • Biotechnology
  • Ecology, Evolution, Behavior and Systematics
  • Ecology
  • Genetics


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