Editing Long-term memory (section)

===[[DNA methylation]] and [[DNA demethylation|demethylation]]===

Rats exposed to an intense learning event may retain a life-long memory of the event, even after a single training session. The LTM of such an event appears to be initially stored in the hippocampus, but this storage is transient. Much of the long-term storage of the memory seems to take place in the [[anterior cingulate cortex]].<ref>{{cite journal | pmid = 15131309 | doi=10.1126/science.1094804 | volume=304 | title=The involvement of the anterior cingulate cortex in remote contextual fear memory | year=2004 | journal=Science | pages=881–3 | last1 = Frankland | first1 = PW | last2 = Bontempi | first2 = B | last3 = Talton | first3 = LE | last4 = Kaczmarek | first4 = L | last5 = Silva | first5 = AJ | issue=5672 | bibcode = 2004Sci...304..881F| s2cid=15893863 }}</ref> When such an exposure was experimentally applied, more than 5,000 differently methylated DNA regions appeared in the [[hippocampus]] [[neuron]]al [[genome]] of the rats at one and at 24 hours after training.<ref>{{cite journal | pmid = 28620075 | doi=10.1101/lm.045112.117 | volume=24 | title=Experience-dependent epigenomic reorganization in the hippocampus | pmc=5473107 | year=2017 | journal=Learn Mem | pages=278–288 | last1 = Duke | first1 = CG | last2 = Kennedy | first2 = AJ | last3 = Gavin | first3 = CF | last4 = Day | first4 = JJ | last5 = Sweatt | first5 = JD| issue=7 }}</ref> These alterations in methylation pattern occurred at many [[gene]]s that were [[downregulation and upregulation|down-regulated]], often due to the formation of new [[5-methylcytosine]] sites in CpG rich regions of the genome. Furthermore, many other genes were [[downregulation and upregulation|upregulated]], likely often due to hypomethylation. Hypomethylation often results from the removal of methyl groups from previously existing [[5-methylcytosine]]s in DNA. Demethylation is carried out by several proteins acting in concert, including [[TET enzymes]] as well as enzymes of the DNA [[base excision repair]] pathway (see [[Epigenetics in learning and memory]]). The pattern of induced and repressed genes in brain neurons subsequent to an intense learning event likely provides the molecular basis for a LTM of the event.