Editing Hippocampus (section)

=== Role in memory ===
{{See also|Amnesia|Epigenetics in learning and memory}}
The hippocampus is essential for the formation of [[explicit memory]], also known as declarative memory. [[Episodic memory]], and [[semantic memory]] are the two components of explicit memory.
<ref name="Huang">{{cite journal |vauthors=Huang CC, Rolls ET, Hsu CH, Feng J, Lin CP |title=Extensive Cortical Connectivity of the Human Hippocampal Memory System: Beyond the "What" and "Where" Dual Stream Model |journal=Cereb Cortex |volume=31 |issue=10 |pages=4652–4669 |date=August 2021 |pmid=34013342 |pmc=8866812 |doi=10.1093/cercor/bhab113 |url=}}</ref>
The hippocampus also encodes emotional context from the [[amygdala]]. This is partly why returning to a location where an emotional event occurred may evoke that emotion. There is a deep emotional connection between episodic memories and places.<ref>{{Cite book|title=Learning and Memory From Brain to Behavior | edition = Second | vauthors = Gluck M, Mercado E, Myers C  |publisher=Kevin Feyen|year=2014|isbn=978-1-4292-4014-7|location=New York|pages=416}}</ref>

Due to [[bilateral symmetry]] the brain has a hippocampus in each [[cerebral hemisphere]]. If damage to the hippocampus occurs in only one hemisphere, leaving the structure intact in the other hemisphere, the brain can retain near-normal memory functioning.<ref>{{cite journal | vauthors = Di Gennaro G, Grammaldo LG, Quarato PP, Esposito V, Mascia A, Sparano A, Meldolesi GN, Picardi A | title = Severe amnesia following bilateral medial temporal lobe damage occurring on two distinct occasions | journal = Neurological Sciences | volume = 27 | issue = 2 | pages = 129–133 | date = June 2006 | pmid = 16816912 | doi = 10.1007/s10072-006-0614-y | s2cid = 7741607 }}</ref> Severe damage to the hippocampi in both hemispheres results in profound difficulties in forming new memories ([[anterograde amnesia]]) and often also affects memories formed before the damage occurred ([[retrograde amnesia]]). Although the retrograde effect normally extends many years back before the brain damage, in some cases older memories remain. This retention of older memories leads to the idea that [[Memory consolidation|consolidation]] over time involves the transfer of memories out of the hippocampus to other parts of the brain.<ref name="SquireSchacter">{{cite book | vauthors = Squire LR, Schacter DL | title = The Neuropsychology of Memory | year =2002 | publisher = Guilford Press | ref = refSquire2002}}</ref>{{rp|Ch. 1}} Experiments using intrahippocampal transplantation of hippocampal cells in primates with neurotoxic lesions of the hippocampus have shown that the hippocampus is required for the formation and recall, but not the storage, of memories.<ref name="pmid10581225">{{cite journal | vauthors = Virley D, Ridley RM, Sinden JD, Kershaw TR, Harland S, Rashid T, French S, Sowinski P, Gray JA, Lantos PL, Hodges H | title = Primary CA1 and conditionally immortal MHP36 cell grafts restore conditional discrimination learning and recall in marmosets after excitotoxic lesions of the hippocampal CA1 field | journal = Brain: A Journal of Neurology | volume = 122 | issue = 12 | pages = 2321–2335 | date = December 1999 | pmid = 10581225 | doi = 10.1093/brain/122.12.2321 | doi-access = free }}</ref> It has been shown that a decrease in the volume of various parts of the hippocampus leads to specific memory impairments. In particular, efficiency of verbal memory retention is related to the anterior parts of the right and left hippocampus. The right head of the hippocampus is more involved in executive functions and regulation during verbal memory recall. The tail of the left hippocampus tends to be closely related to verbal memory capacity.<ref name="Sozinova-2008">{{cite journal| vauthors = Sozinova EV, Kozlovskiy SA, Vartanov AV, Skvortsova VB, Pirogov YA, Anisimov NV, Kupriyanov DA |date=September 2008|title=The role of hippocampal parts in verbal memory and activation processes|journal=International Journal of Psychophysiology|volume=69|issue=3|pages=312|doi=10.1016/j.ijpsycho.2008.05.328}}</ref>

Damage to the hippocampus does not affect some types of memory, such as the ability to learn new skills (playing a musical instrument or solving certain types of puzzles, for example). This fact suggests that such abilities depend on different types of memory such as [[procedural memory]] in [[implicit memory]] function, implicating different brain regions. Furthermore, amnesic patients frequently show implicit memory for experiences even in the absence of conscious knowledge. For example, patients asked to guess which of two faces they have seen most recently may give the correct answer most of the time in spite of stating that they have never seen either of the faces before. Some researchers distinguish between conscious ''recollection'', which depends on the hippocampus, and ''familiarity'', which depends on portions of the medial temporal lobe.<ref>{{cite journal | vauthors = Diana RA, Yonelinas AP, Ranganath C | title = Imaging recollection and familiarity in the medial temporal lobe: a three-component model | journal = Trends in Cognitive Sciences | volume = 11 | issue = 9 | pages = 379–386 | date = September 2007 | pmid = 17707683 | doi = 10.1016/j.tics.2007.08.001 | ref = refDiana2007 | s2cid = 1443998 }}</ref> A study claims to have confirmed that the hippocampus is not associated with implicit memory.<ref name="Steinkrauss">{{cite journal |vauthors=Steinkrauss AC, Slotnick SD |title=Is implicit memory associated with the hippocampus? |journal=Cogn Neurosci |volume=15 |issue=2 |pages=56–70 |date=April 2024 |pmid=38368598 |doi=10.1080/17588928.2024.2315816 |url=}}</ref> But other sources say the question is still up for debate (as of 2024).<ref name="Slotnik">{{cite journal |vauthors=Slotnick SD |title=The hippocampus and implicit memory |journal=Cogn Neurosci |volume=15 |issue=2 |pages=25–26 |date=April 2024 |pmid=38767113 |doi=10.1080/17588928.2024.2354706 |url=}}</ref>

When rats are exposed to an intense learning event, they may retain a life-long memory of the event even after a single training session. The memory of such an event appears to be first 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 | vauthors = Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ | title = The involvement of the anterior cingulate cortex in remote contextual fear memory | journal = Science | volume = 304 | issue = 5672 | pages = 881–883 | date = May 2004 | pmid = 15131309 | doi = 10.1126/science.1094804 | s2cid = 15893863 | bibcode = 2004Sci...304..881F }}</ref> When such an intense learning event was experimentally applied, more than 5,000 [[Differentially methylated region|differently methylated DNA regions]] appeared in the hippocampus [[neuron]]al [[genome]] of the rats at one hour and at 24 hours after training.<ref>{{cite journal | vauthors = Duke CG, Kennedy AJ, Gavin CF, Day JJ, Sweatt JD | title = Experience-dependent epigenomic reorganization in the hippocampus | journal = Learning & Memory | volume = 24 | issue = 7 | pages = 278–288 | date = July 2017 | pmid = 28620075 | pmc = 5473107 | doi = 10.1101/lm.045112.117 }}</ref> These alterations in [[DNA methylation|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 site|CpG rich regions]] of the genome. Furthermore, many other genes were [[downregulation and upregulation|upregulated]], likely often due to the [[DNA demethylation|removal of methyl groups]] from previously existing [[5-methylcytosine]]s (5mCs) in DNA. Demethylation of 5mC can be carried out by several proteins acting in concert, including [[TET enzymes]]<ref name="Rasmussen_2016">{{cite journal | vauthors = Rasmussen KD, Helin K | title = Role of TET enzymes in DNA methylation, development, and cancer | journal = Genes & Development | volume = 30 | issue = 7 | pages = 733–750 | date = April 2016 | pmid = 27036965 | pmc = 4826392 | doi = 10.1101/gad.276568.115 }}</ref><ref name="Melamed_2018">{{cite journal | vauthors = Melamed P, Yosefzon Y, David C, Tsukerman A, Pnueli L | title = Tet Enzymes, Variants, and Differential Effects on Function | journal = Frontiers in Cell and Developmental Biology | volume = 6 | issue = | pages = 22 | date = 2018 | pmid = 29556496 | doi = 10.3389/fcell.2018.00022 | doi-access = free | pmc = 5844914 }}</ref> as well as enzymes of the DNA [[base excision repair]] pathway.<ref name="Drohat_2016">{{cite journal | vauthors = Drohat AC, Coey CT | title = Role of Base Excision "Repair" Enzymes in Erasing Epigenetic Marks from DNA | journal = Chemical Reviews | volume = 116 | issue = 20 | pages = 12711–12729 | date = October 2016 | pmid = 27501078 | pmc = 5299066 | doi = 10.1021/acs.chemrev.6b00191 }}</ref>

====Between systems model====
The '''between-systems memory interference model''' describes the inhibition of non-hippocampal systems of memory during concurrent hippocampal activity.<ref name="Packard_2013">{{cite journal | vauthors = Packard MG, Goodman J | title = Factors that influence the relative use of multiple memory systems | journal = Hippocampus | volume = 23 | issue = 11 | pages = 1044–1052 | date = November 2013 | pmid = 23929809 | doi = 10.1002/hipo.22178 }}</ref>  Specifically it was found that when the hippocampus was inactive, non-hippocampal systems located elsewhere in the brain were found to [[Memory consolidation|consolidate]] memory in its place. However, when the hippocampus was reactivated, [[Engram (neuropsychology)|memory traces]] consolidated by non-hippocampal systems were not recalled, suggesting that the hippocampus interferes with [[long-term memory]] consolidation in other memory-related systems.<ref>{{cite journal | vauthors = Sparks FT, Lehmann H, Sutherland RJ | title = Between-systems memory interference during retrieval | journal = The European Journal of Neuroscience | volume = 34 | issue = 5 | pages = 780–786 | date = September 2011 | pmid = 21896061 | doi = 10.1111/j.1460-9568.2011.07796.x | s2cid = 25745773 }}</ref>

One of the major implications that this model illustrates is the dominant effects of the hippocampus on non-hippocampal networks when information is incongruent. With this information in mind, future directions could lead towards the study of these non-hippocampal memory systems through hippocampal inactivation, further expanding the labile constructs of memory. Additionally, many theories of memory are holistically based around the hippocampus. This model could add beneficial information to hippocampal research and memory theories such as the [[multiple trace theory]].<ref name="Moscovitch_2005">{{cite journal | vauthors = Moscovitch M, Rosenbaum RS, Gilboa A, Addis DR, Westmacott R, Grady C, McAndrews MP, Levine B, Black S, Winocur G, Nadel L | title = Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory | journal = Journal of Anatomy | volume = 207 | issue = 1 | pages = 35–66 | date = July 2005 | pmid = 16011544 | pmc = 1571502 | doi = 10.1111/j.1469-7580.2005.00421.x | department = Review }}</ref><ref name = "Moscovitch_2024">{{cite book | vauthors = Moscovitch M, Gilboa A | chapter = Systems consolidation, transformation and reorganization: Multiple trace theory, trace transformation theory and their competitors. | veditors = Kahana MJ, Wagner AD | title = The Oxford Handbook of Human Memory, Two Volume Pack: Foundations and Applications | publisher = Oxford University Press | date = June 2024 | isbn = 978-0-19-091798-2 | doi = 10.1093/oxfordhb/9780190917982.013.43 | department = Review }}</ref> Lastly, the between-system memory interference model allows researchers to evaluate their results on a [[Systems neuroscience|multiple-systems model]], suggesting that some effects may not be simply mediated by one portion of the brain.<ref name="Ferbinteanu_2019">{{cite journal | vauthors = Ferbinteanu J | title = Memory systems 2018 - Towards a new paradigm | journal = Neurobiology of Learning and Memory | volume = 157 | issue = | pages = 61–78 | date = January 2019 | pmid = 30439565 | pmc = 6389412 | doi = 10.1016/j.nlm.2018.11.005 | department = Review }}</ref>