text: Learning and memory have levels of permanence, differing from other mental processes such as thought, language, and consciousness, which are temporary in nature. Learning and memory can be either accumulated slowly (multiplication tables) or rapidly (touching a hot stove), but once attained, can be recalled into conscious use for a long time.  Rats subjected to one instance of contextual fear conditioning create an especially strong long-term memory. At 24 hours after training, 9.17% of the genes in the genomes of rat hippocampus neurons were found to be differentially methylated.  This included more than 2,000 differentially methylated genes at 24 hours after training, with over 500 genes being demethylated.  Similar results to that in the rat hippocampus were also obtained in mice with contextual fear conditioning. 
  The hippocampus region of the brain is where contextual fear memories are first stored (see Figure), but this storage is transient and does not remain in the hippocampus.  In rats contextual fear conditioning is abolished when the hippocampus is subjected to hippocampectomy just one day after conditioning, but rats retain a considerable amount of contextual fear when hippocampectomy is delayed by four weeks.  In mice, examined at 4 weeks after conditioning, the hippocampus methylations and demethylations were reversed (the hippocampus is needed to form memories but memories are not stored there) while substantial differential CpG methylation and demethylation occurred in cortical neurons during memory maintenance.  There were 1,223 differentially methylated genes in the anterior cingulate cortex (see Figure) of mice four weeks after contextual fear conditioning. Thus, while there were many methylations in the hippocampus shortly after memory was formed, all these hippocampus methylations were demethylated as soon as four weeks later.
  Li et al. reported one example of the relationship between expression of a TET protein, demethylation and memory while using extinction training.  Extinction training is the disappearance of a previously learned behavior when the behavior is not reinforced.  
  A comparison between infralimbic prefrontal cortex (ILPFC) neuron samples derived from mice trained to fear an auditory cue and extinction-trained mice revealed dramatic experience-dependent genome-wide differences in the accumulation of 5-hmC in the ILPFC in response to learning.   Extinction training led to a significant increase in TET3 messenger RNA levels within cortical neurons.  TET3 was selectively activated within the adult neo-cortex in an experience-dependent manner.  
  A short hairpin RNA (shRNA) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference.  Mice trained in the presence of TET3-targeted shRNA showed a significant impairment in fear extinction memory.