• Contextual fear memory;
  • DNA methylation;
  • gene expression;
  • hippocampus;
  • Nr4a1;
  • sex differences

Long-term memory formation requires de novo protein synthesis and gene transcription. During contextual long-term memory formation brain-derived neurotrophic factor (BDNF) gene expression changes in conjunction with alterations of DNA methylation in the Bdnf gene. However, little is known about the molecular mechanisms underlying the maintenance and persistence of contextual long-term memory. Here, we examined the transcription of specific Bdnf exons in the hippocampus for long periods after contextual fear conditioning. We found changes in transcription lasting for at least 24 h after contextual fear conditioning, with some sex-specific effects. In addition, hypomethylation at a CpG site in CpG island 2 located at the end of Bdnf exon III sequence was detected at 0.5 h and maintained for up to 24 h after contextual fear conditioning. The identification of these long-lasting changes in transcription and DNA methylation at the Bdnf gene suggests that BDNF might have a role for storage of contextual long-term memory in the hippocampus.