Editing Hippocampus (section)

== Function ==

===Theories===
Three main theories of hippocampal function have been in dominance: [[inhibitory control|response inhibition]], [[episodic memory]], and [[spatial cognition]]. The response inhibition theory (caricatured by [[John O'Keefe (neuroscientist)|John O'Keefe]] and [[Lynn Nadel]] as "slam on the brakes!") was very popular up to the 1960s.<ref>{{cite journal | vauthors = Nadel L, O'Keefe J, Black A | title = Slam on the brakes: a critique of Altman, Brunner, and Bayer's response-inhibition model of hippocampal function | journal = Behavioral Biology | volume = 14 | issue = 2 | pages = 151–162 | date = June 1975 | pmid = 1137539 | doi = 10.1016/S0091-6773(75)90148-0 | ref = refNadel1975 }}</ref>  It was based largely on two observations: first, that animals with hippocampal damage tend to be [[hyperactivity|hyperactive]]; second, that animals with hippocampal damage often have difficulty learning to inhibit previously learnt responses, especially if the response requires remaining quiet as in a [[Avoidance learning#Active avoidance, passive avoidance, and escape responses|passive avoidance]] test. British psychologist [[Jeffrey Alan Gray|Jeffrey Gray]] developed this line of thought into a complete theory of the role of the hippocampus in [[anxiety]], called the [[behavioral inhibition system]].<ref>{{cite book | vauthors = Gray JA, McNaughton N | title = The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal System | year = 2000 | publisher = Oxford University Press | ref = refGray2000 }}</ref><ref name="Bosecke2025">{{cite journal |vauthors=Bosecke C, Ng M, Dastgheib Z, Lithgow BJ |title=Perspective: Hippocampal theta rhythm as a potential vestibuloacoustic biomarker of anxiety |journal=Eur J Neurosci |volume=61 |issue=1 |pages=e16641 |date=January 2025 |pmid=39662900 |pmc=11664906 |doi=10.1111/ejn.16641 |url=}}</ref>

The second major line of thought relates the hippocampus to memory. Although it had historical precursors, this idea derived its main impetus from a famous report by American neurosurgeon [[William Beecher Scoville]] and British-Canadian neuropsychologist [[Brenda Milner]].<ref name="Scoville">{{cite journal | vauthors = Scoville WB, Milner B | title = Loss of recent memory after bilateral hippocampal lesions | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 20 | issue = 1 | pages = 11–21 | date = February 1957 | pmid = 13406589 | pmc = 497229 | doi = 10.1136/jnnp.20.1.11 | ref = refScoville1957 }}</ref> It described the results of surgical destruction of the hippocampi when trying to relieve [[epileptic seizure]]s in an American man [[Henry Molaison]], known until his death in 2008 as "Patient H.M."<ref name="Squire2009">{{cite journal |vauthors=Squire LR |title=The legacy of patient H.M. for neuroscience |journal=Neuron |volume=61 |issue=1 |pages=6–9 |date=January 2009 |pmid=19146808 |pmc=2649674 |doi=10.1016/j.neuron.2008.12.023 |url=}}</ref><ref name="HMObit">{{cite news | vauthors = Carey B | title=H. M., an Unforgettable Amnesiac, Dies at 82 | work=The New York Times | date=2008-12-04 | url=https://www.nytimes.com/2008/12/05/us/05hm.html | access-date=2009-04-27 | ref=refhMObit | archive-date=2018-06-13 | archive-url=https://web.archive.org/web/20180613184944/https://www.nytimes.com/2008/12/05/us/05hm.html | url-status=live }}</ref> The unexpected outcome of the surgery was severe [[anterograde amnesia|anterograde]], and partial [[retrograde amnesia]]; Molaison was unable to form new [[episodic memories]] after his surgery and could not remember any events that occurred just before his surgery, but he did retain memories of events that occurred many years earlier extending back into his childhood. This case attracted such widespread professional interest that Molaison became the most intensively studied subject in medical history.<ref name ="Squire2009"/> 
[[File:Rats_and_cognitive_maps_and_maze.png|thumb|314x314px|Rats and [[cognitive map]]s]]
The third important theory of hippocampal function relates the hippocampus to space, and [[spatial memory]], with the idea of a [[cognitive map]] first proposed by American psychologist [[Edward C. Tolman|E.C. Tolman]]. This theory was followed further by O'Keefe, and in 1971, he and his student Dostrovsky discovered neurons, in the rat hippocampus that seemed to show activity related to the rat's location within its environment. The neurons were described as [[place cell]]s.<ref>{{cite journal | vauthors = O'Keefe J, Dostrovsky J | title = The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat | journal = Brain Research | volume = 34 | issue = 1 | pages = 171–175 | date = November 1971 | pmid = 5124915 | doi = 10.1016/0006-8993(71)90358-1 | ref = refOKeefe1971 }}</ref> A book was later produced in 1978, ''The Hippocampus as a Cognitive Map'' written by O'Keefe and Nadel.<ref name="O'Keefe">{{cite book | vauthors = O'Keefe J, Nadel L | title = The Hippocampus as a Cognitive Map | year = 1978 | publisher = Oxford University Press | url = http://www.cognitivemap.net/HCMpdf/HCMChapters.html | ref = refOKeefe1978 | access-date = 2008-10-23 | archive-date = 2011-03-24 | archive-url = https://web.archive.org/web/20110324042731/http://www.cognitivemap.net/HCMpdf/HCMChapters.html | url-status = live }}</ref> It has been generally agreed that the hippocampus plays a key role in spatial coding but the details are widely debated.<ref name=Moser2008>{{cite journal | vauthors = Moser EI, Kropff E, Moser MB | title = Place cells, grid cells, and the brain's spatial representation system | journal = Annual Review of Neuroscience | volume = 31 | pages = 69–89 | year = 2008 | pmid = 18284371 | doi = 10.1146/annurev.neuro.31.061307.090723 | ref = refMoser2008 | s2cid = 16036900 }}</ref>

Research has focused on trying to bridge the disconnect between the two main views of hippocampal function as being split between memory and spatial cognition. In some studies, these areas have been expanded to the point of near convergence. In an attempt to reconcile the two disparate views, it is suggested that a broader view of the hippocampal function is taken and seen to have a role that encompasses both the organization of experience ([[mental mapping]], as per Tolman's original concept in 1948) and the directional behavior seen as being involved in all areas of cognition, so that the function of the hippocampus can be viewed as a broader system that incorporates both the memory and the spatial perspectives in its role that involves the use of a wide scope of cognitive maps.<ref>{{cite journal | vauthors = Schiller D, Eichenbaum H, Buffalo EA, Davachi L, Foster DJ, Leutgeb S, Ranganath C | title = Memory and Space: Towards an Understanding of the Cognitive Map | journal = The Journal of Neuroscience | volume = 35 | issue = 41 | pages = 13904–13911 | date = October 2015 | pmid = 26468191 | pmc = 6608181 | doi = 10.1523/JNEUROSCI.2618-15.2015 }}</ref><ref>{{Cite journal |last1=Tse |first1=Dorothy |last2=Langston |first2=Rosamund F. |last3=Kakeyama |first3=Masaki |last4=Bethus |first4=Ingrid |last5=Spooner |first5=Patrick A. |last6=Wood |first6=Emma R. |last7=Witter |first7=Menno P. |last8=Morris |first8=Richard G. M. |date=2007-04-06 |title=Schemas and Memory Consolidation |url=https://www.science.org/doi/10.1126/science.1135935 |journal=Science |volume=316 |issue=5821 |pages=76–82 |doi=10.1126/science.1135935|pmid=17412951 |bibcode=2007Sci...316...76T }}</ref><ref>{{Cite journal |last1=Tse |first1=Dorothy |last2=Takeuchi |first2=Tomonori |last3=Kakeyama |first3=Masaki |last4=Kajii |first4=Yasushi |last5=Okuno |first5=Hiroyuki |last6=Tohyama |first6=Chiharu |last7=Bito |first7=Haruhiko |last8=Morris |first8=Richard G. M. |date=2011-08-12 |title=Schema-dependent gene activation and memory encoding in neocortex |url=https://pubmed.ncbi.nlm.nih.gov/21737703/ |journal=Science |volume=333 |issue=6044 |pages=891–895 |doi=10.1126/science.1205274 |issn=1095-9203 |pmid=21737703|bibcode=2011Sci...333..891T }}</ref><ref>{{Cite journal |last1=Miller |first1=Adam M. P. |last2=Jacob |first2=Alex D. |last3=Ramsaran |first3=Adam I. |last4=De Snoo |first4=Mitchell L. |last5=Josselyn |first5=Sheena A. |last6=Frankland |first6=Paul W. |date=2023-06-21 |title=Emergence of a predictive model in the hippocampus |journal=Neuron |volume=111 |issue=12 |pages=1952–1965.e5 |doi=10.1016/j.neuron.2023.03.011 |pmid=37015224 |issn=0896-6273|pmc=10293047 }}</ref> This relates to the [[purposive behaviorism]] born of Tolman's original goal of identifying the complex cognitive mechanisms and purposes that guided behavior.<ref>{{cite journal | vauthors = Eichenbaum H | title = The hippocampus and declarative memory: Cognitive mechanisms and neural codes | journal = Behavioural Brain Research | volume = 127 | issue = 1–2 | pages = 199–207 | date = December 2001 | pmid = 11718892 | doi = 10.1016/s0166-4328(01)00365-5 | s2cid = 20843130 }}</ref>

It has also been proposed that the spiking activity of hippocampal neurons is associated spatially, and it was suggested that the mechanisms of memory and planning both evolved from mechanisms of navigation and that their neuronal algorithms were basically the same.<ref>{{cite journal | vauthors = Buzsáki G, Moser EI | title = Memory, navigation and theta rhythm in the hippocampal-entorhinal system | journal = Nature Neuroscience | volume = 16 | issue = 2 | pages = 130–138 | date = February 2013 | pmid = 23354386 | pmc = 4079500 | doi = 10.1038/nn.3304 }}</ref>

Many studies have made use of [[neuroimaging]] techniques such as [[functional magnetic resonance imaging]] (fMRI), and a functional role in [[approach-avoidance conflict]] has been noted. The anterior hippocampus is seen to be involved in decision-making under approach-avoidance conflict processing. It is suggested that the memory, spatial cognition, and conflict processing functions may be seen as working together and not mutually exclusive.<ref name="ReferenceB">{{cite journal | vauthors = Ito R, Lee AC | title = The role of the hippocampus in approach-avoidance conflict decision-making: Evidence from rodent and human studies | journal = Behavioural Brain Research | volume = 313 | pages = 345–357 | date = October 2016 | pmid = 27457133 | doi = 10.1016/j.bbr.2016.07.039 | doi-access = free }}</ref>

=== 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>

=== Role in spatial memory and navigation ===
{{Main|Place cell}}
[[File:Place Cell Spiking Activity Example.png|thumb|300px|right| Spatial [[firing pattern]]s of eight [[place cell]]s recorded from the [[#Structure|CA1]] layer of a rat. The rat ran back and forth along an elevated track, stopping at each end to eat a small food reward. Dots indicate positions where [[action potential]]s were recorded, with color indicating which neuron emitted that action potential.]]
[[File:HIPO-33-533-g013.jpg|thumb|300px|Hippocampal connections in spatial cognition]]
There are several types of [[Navigation#Navigation in spatial cognition|navigational]] cells in the brain that are either in the hippocampus itself or are strongly connected to it. They include the [[place cell]]s, [[speed cells]] present in the [[entorhinal cortex|medial entorhinal cortex]], [[head direction cell]]s, [[grid cell]]s, and [[boundary cell]]s.<ref name=Moser2008 /><ref>{{cite journal | vauthors = Solstad T, Boccara CN, Kropff E, Moser MB, Moser EI | title = Representation of geometric borders in the entorhinal cortex | journal = Science | volume = 322 | issue = 5909 | pages = 1865–1868 | date = December 2008 | pmid = 19095945 | doi = 10.1126/science.1166466 | ref = refSolstad2008 | s2cid = 260976755 | doi-access =  | bibcode = 2008Sci...322.1865S }}</ref> Together these cells form a network that serves as [[spatial memory]].

The first of these types of cell discovered in the 1970s were the place cells, which led to the idea of the hippocampus acting to give a neural representation of the environment in a [[cognitive map]].<ref name="O'Keefe" /> When the hippocampus is dysfunctional, orientation is affected; people may have difficulty in remembering how they arrived at a location and how to proceed further. Getting lost is a common symptom of amnesia.<ref>{{cite journal | vauthors = Chiu YC, Algase D, Whall A, Liang J, Liu HC, Lin KN, Wang PN | title = Getting lost: directed attention and executive functions in early Alzheimer's disease patients | journal = Dementia and Geriatric Cognitive Disorders | volume = 17 | issue = 3 | pages = 174–180 | year = 2004 | pmid = 14739541 | doi = 10.1159/000076353 | ref = refChiu2004 | s2cid = 20454273 }}</ref> Studies with animals have shown that an intact hippocampus is required for initial learning and long-term retention of some spatial memory tasks, in particular ones that require finding the way to a hidden goal.<ref>{{cite journal | vauthors = Morris RG, Garrud P, Rawlins JN, O'Keefe J | title = Place navigation impaired in rats with hippocampal lesions | journal = Nature | volume = 297 | issue = 5868 | pages = 681–683 | date = June 1982 | pmid = 7088155 | doi = 10.1038/297681a0 | ref = refMorris1982 | s2cid = 4242147 | bibcode = 1982Natur.297..681M }}</ref><ref>{{cite journal | vauthors = Sutherland RJ, Kolb B, Whishaw IQ | title = Spatial mapping: definitive disruption by hippocampal or medial frontal cortical damage in the rat | journal = Neuroscience Letters | volume = 31 | issue = 3 | pages = 271–276 | date = August 1982 | pmid = 7133562 | doi = 10.1016/0304-3940(82)90032-5 | ref = refSutherland1982 | s2cid = 20203374 }}</ref><ref>{{cite journal | vauthors = Sutherland RJ, Weisend MP, Mumby D, Astur RS, Hanlon FM, Koerner A, Thomas MJ, Wu Y, Moses SN, Cole C, Hamilton DA, Hoesing JM | title = Retrograde amnesia after hippocampal damage: recent vs. remote memories in two tasks | journal = Hippocampus | volume = 11 | issue = 1 | pages = 27–42 | year = 2001 | pmid = 11261770 | doi = 10.1002/1098-1063(2001)11:1<27::AID-HIPO1017>3.0.CO;2-4 | ref = refSutherland2001 | s2cid = 142515 }}</ref><ref>{{cite journal | vauthors = Clark RE, Broadbent NJ, Squire LR | title = Hippocampus and remote spatial memory in rats | journal = Hippocampus | volume = 15 | issue = 2 | pages = 260–272 | year = 2005 | pmid = 15523608 | pmc = 2754168 | doi = 10.1002/hipo.20056 | ref = refClark2005 }}</ref>

Studies on freely moving rats and mice have shown many hippocampal [[neuron]]s to act as [[place cell]]s that cluster in [[Place cell#Place fields|place fields]], and these fire bursts of [[action potential]]s when the animal passes through a particular location.<ref name="Eichenbaum_2017">{{cite journal | vauthors = Eichenbaum H | title = The role of the hippocampus in navigation is memory | journal = Journal of Neurophysiology | volume = 117 | issue = 4 | pages = 1785–1796 | date = April 2017 | pmid = 28148640 | pmc = 5384971 | doi = 10.1152/jn.00005.2017 }}</ref>
Hippocampal place cells interact extensively with head direction cells, whose activity acts as an inertial compass, and conjecturally with grid cells in the neighboring entorhinal cortex.<ref>{{cite book | vauthors = Taube JS, Yoder RM | chapter = The impact of vestibular signals on cells responsible for orientation and navigation. | doi = 10.1016/B978-0-12-809324-5.23894-7 | veditors = Fritzsch B |title=The Senses; Volume 6: Vestibular System and Balance |date=2020 | pages = 496–511 |publisher=Elsevier Science & Technology |location=San Diego |isbn=978-0-12-805409-3 |edition=2nd }}</ref> Speed cells are thought to provide input to the hippocampal grid cells.<ref>{{cite web | vauthors = Moser MB | author-link = May-Britt Moser | title = Grid cells, place cells and memory. | work = Nobel Lecture | date = 7 December 2014 | url = https://www.nobelprize.org/uploads/2018/06/may-britt-moser-lecture-slides.pdf | publisher = The Nobel Foundation | location = Stockholm, Sweden }}</ref> This place-related neural activity in the hippocampus has also been reported in monkeys that were moved around a room whilst in a restraint chair.<ref>{{cite journal | vauthors = Matsumura N, Nishijo H, Tamura R, Eifuku S, Endo S, Ono T | title = Spatial- and task-dependent neuronal responses during real and virtual translocation in the monkey hippocampal formation | journal = The Journal of Neuroscience | volume = 19 | issue = 6 | pages = 2381–2393 | date = March 1999 | pmid = 10066288 | pmc = 6782547 | doi = 10.1523/JNEUROSCI.19-06-02381.1999 | ref = refMatsumura1999 }}</ref> However, the place cells may have fired in relation to where the monkey was looking rather than to its actual location in the room.<ref>{{cite journal | vauthors = Rolls ET, Xiang JZ | title = Spatial view cells in the primate hippocampus and memory recall | journal = Reviews in the Neurosciences | volume = 17 | issue = 1–2 | pages = 175–200 | year = 2006 | pmid = 16703951 | doi = 10.1515/REVNEURO.2006.17.1-2.175 | ref = refRolls2006 | s2cid = 147636287 }}</ref> Over many years, many studies have been carried out on place-responses in rodents, which have given a large amount of information.<ref name=Moser2008 /> Place cell responses are shown by [[pyramidal cell]]s in the hippocampus and by [[granule cell]]s in the [[dentate gyrus]]. Other cells in smaller proportion are inhibitory [[interneuron]]s, and these often show place-related variations in their firing rate that are much weaker. There is little, if any, spatial topography in the representation; in general, cells lying next to each other in the hippocampus have uncorrelated spatial [[firing pattern]]s. Place cells are typically almost silent when a rat is moving around outside the place field but reach sustained rates as high as 40 [[hertz|Hz]] when the rat is near the center. Neural activity sampled from 30 to 40 randomly chosen place cells carries enough information to allow a rat's location to be reconstructed with high confidence. The size of place fields varies in a gradient along the length of the hippocampus, with cells at the dorsal end showing the smallest fields, cells near the center showing larger fields, and cells at the ventral tip showing fields that cover the entire environment.<ref name=Moser2008 /> In some cases, the firing rate of hippocampal cells depends not only on place but also the direction a rat is moving, the destination toward which it is traveling, or other task-related variables.<ref>{{cite journal | vauthors = Smith DM, Mizumori SJ | title = Hippocampal place cells, context, and episodic memory | journal = Hippocampus | volume = 16 | issue = 9 | pages = 716–729 | year = 2006 | pmid = 16897724 | doi = 10.1002/hipo.20208 | ref = refSmith2006 | s2cid = 720574 | citeseerx = 10.1.1.141.1450 }}</ref> The firing of place cells is timed in relation to local [[#Theta rhythm|theta waves]], a [[spatiotemporal]]  process termed [[phase precession]].<ref name="Lian2022">{{cite journal |vauthors=Lian Y, Burkitt AN |title=Learning Spatiotemporal Properties of Hippocampal Place Cells |journal=eNeuro |volume=9 |issue=4 |pages= |date=2022 |pmid=35760526 |pmc=9282168 |doi=10.1523/ENEURO.0519-21.2022 |url=}}</ref><ref name="OKeefe1993">{{cite journal | vauthors = O'Keefe J, Recce ML | title = Phase relationship between hippocampal place units and the EEG theta rhythm | journal = Hippocampus | volume = 3 | issue = 3 | pages = 317–330 | date = July 1993 | pmid = 8353611 | doi = 10.1002/hipo.450030307 | s2cid = 6539236 }}</ref>

Cells with location-specific firing patterns have been reported during a study of people with [[drug-resistant epilepsy]]. They were undergoing an invasive procedure to localize the source of their [[seizure]]s, with a view to surgical resection. They had diagnostic electrodes implanted in their hippocampi and then used a computer to move around in a [[virtual reality]] town.<ref name="Ekstrom">{{cite journal | vauthors = Ekstrom AD, Kahana MJ, Caplan JB, Fields TA, Isham EA, Newman EL, Fried I | title = Cellular networks underlying human spatial navigation | journal = Nature | volume = 425 | issue = 6954 | pages = 184–188 | date = September 2003 | pmid = 12968182 | doi = 10.1038/nature01964 | url = http://memory.psych.upenn.edu/Publications#EkstEtal03 | ref = refEkstrom2003 | access-date = 2013-01-24 | url-status = live | format = PDF | s2cid = 1673654 | citeseerx = 10.1.1.408.4443 | bibcode = 2003Natur.425..184E | archive-url = https://web.archive.org/web/20211020000026/http://memory.psych.upenn.edu/Publications#EkstEtal03 | archive-date = 2021-10-20 }}</ref> Similar [[neuroimaging|brain imaging]] studies in [[Navigation#Navigation in spatial cognition|navigation]] have shown the hippocampus to be active.<ref>{{cite journal | vauthors = Duarte IC, Ferreira C, Marques J, Castelo-Branco M | title = Anterior/posterior competitive deactivation/activation dichotomy in the human hippocampus as revealed by a 3D navigation task | journal = PLOS ONE | volume = 9 | issue = 1 | pages = e86213 | date = 2014-01-27 | pmid = 24475088 | pmc = 3903506 | doi = 10.1371/journal.pone.0086213 | doi-access = free | bibcode = 2014PLoSO...986213D }}</ref> A study was carried out on taxi drivers. London's [[Hackney carriage|black cab]] drivers need to learn the locations of a large number of places and the fastest routes between them in order to pass a strict test known as [[Taxicabs of the United Kingdom#The Knowledge|The Knowledge]] in order to gain a license to operate. A study showed that the posterior part of the hippocampus is larger in these drivers than in the general public, and that a positive correlation exists between the length of time served as a driver and the increase in the volume of this part. It was also found the total volume of the hippocampus was unchanged, as the increase seen in the posterior part was made at the expense of the anterior part, which showed a relative decrease in size. There have been no reported adverse effects from this disparity in hippocampal proportions.<ref name="Maguire">{{cite journal | vauthors = Maguire EA, Gadian DG, Johnsrude IS, Good CD, Ashburner J, Frackowiak RS, Frith CD | title = Navigation-related structural change in the hippocampi of taxi drivers | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 8 | pages = 4398–4403 | date = April 2000 | pmid = 10716738 | pmc = 18253 | doi = 10.1073/pnas.070039597 | ref = refMaguireFrith2000 | doi-access = free | bibcode = 2000PNAS...97.4398M }}</ref> Another study showed opposite findings in blind individuals. The anterior part of the right hippocampus was larger and the posterior part was smaller, compared with sighted individuals.<ref>{{cite journal | vauthors = Leporé N, Shi Y, Lepore F, Fortin M, Voss P, Chou YY, Lord C, Lassonde M, Dinov ID, Toga AW, Thompson PM | title = Pattern of hippocampal shape and volume differences in blind subjects | journal = NeuroImage | volume = 46 | issue = 4 | pages = 949–957 | date = July 2009 | pmid = 19285559 | pmc = 2736880 | doi = 10.1016/j.neuroimage.2009.01.071 }}</ref>

===Role in approach-avoidance conflict processing===
{{Further |Reward system}}
[[Approach-avoidance conflict]] happens when a situation is presented that can either be [[Reward system|rewarding]] or punishing, and the ensuing decision-making has been associated with [[anxiety]].<ref name="O'Neil">{{cite journal | vauthors = O'Neil EB, Newsome RN, Li IH, Thavabalasingam S, Ito R, Lee AC | title = Examining the Role of the Human Hippocampus in Approach-Avoidance Decision Making Using a Novel Conflict Paradigm and Multivariate Functional Magnetic Resonance Imaging | journal = The Journal of Neuroscience | volume = 35 | issue = 45 | pages = 15039–15049 | date = November 2015 | pmid = 26558775 | pmc = 6605357 | doi = 10.1523/jneurosci.1915-15.2015 }}</ref> [[fMRI]] findings from studies in approach-avoidance decision-making found evidence for a functional role that is not explained by either long-term memory or spatial cognition. Overall findings showed that the anterior hippocampus is sensitive to conflict, and that it may be part of a larger cortical and subcortical network seen to be important in decision-making in uncertain conditions.<ref name="O'Neil" />

A review makes reference to a number of studies that show the involvement of the hippocampus in conflict tasks. The authors suggest that one challenge is to understand how conflict processing relates to the functions of spatial navigation and memory and how all of these functions need not be mutually exclusive.<ref name="ReferenceB"/>

===Role in social memory===
{{Further|Collective memory}}
The hippocampus has received renewed attention for its role in [[social memory]]. Epileptic human subjects with depth electrodes in the left posterior, left anterior or right anterior hippocampus demonstrate distinct, individual cell responses when presented with faces of presumably recognizable famous people.<ref name="Quiroga et al.">{{cite journal | vauthors = Quiroga RQ, Reddy L, Kreiman G, Koch C, Fried I | title = Invariant visual representation by single neurons in the human brain | journal = Nature | volume = 435 | issue = 7045 | pages = 1102–1107 | date = June 2005 | pmid = 15973409 | doi = 10.1038/nature03687 | bibcode = 2005Natur.435.1102Q | s2cid = 1234637 | url = https://resolver.caltech.edu/CaltechAUTHORS:20130816-103222719 }}</ref> Associations among facial and vocal identity were similarly mapped to the hippocampus of rheseus monkeys. Single neurons in the CA1 and CA3 responded strongly to social stimulus recognition by MRI. The CA2 was not distinguished, and may likely comprise a proportion of the claimed CA1 cells in the study.<ref name="Sliwa et al.">{{cite journal | vauthors = Sliwa J, Planté A, Duhamel JR, Wirth S | title = Independent Neuronal Representation of Facial and Vocal Identity in the Monkey Hippocampus and Inferotemporal Cortex | journal = Cerebral Cortex | volume = 26 | issue = 3 | pages = 950–966 | date = March 2016 | pmid = 25405945 | doi = 10.1093/cercor/bhu257 }}</ref> The dorsal CA2 and ventral CA1 subregions of the hippocampus have been implicated in social memory processing. Genetic inactivation of CA2 pyramidal neurons leads to pronounced loss of social memory, while maintaining intact sociability in mice.<ref name="Hitti and Siegelbaum">{{cite journal | vauthors = Hitti FL, Siegelbaum SA | title = The hippocampal CA2 region is essential for social memory | journal = Nature | volume = 508 | issue = 7494 | pages = 88–92 | date = April 2014 | pmid = 24572357 | pmc = 4000264 | doi = 10.1038/nature13028 | bibcode = 2014Natur.508...88H }}</ref> Similarly, ventral CA1 pyramidal neurons have also been demonstrated as critical for social memory under optogenetic control in mice.<ref name="Okuyama et al.">{{cite journal | vauthors = Okuyama T, Kitamura T, Roy DS, Itohara S, Tonegawa S | title = Ventral CA1 neurons store social memory | journal = Science | volume = 353 | issue = 6307 | pages = 1536–1541 | date = September 2016 | pmid = 27708103 | pmc = 5493325 | doi = 10.1126/science.aaf7003 | bibcode = 2016Sci...353.1536O }}</ref><ref name="Meira et al.">{{cite journal | vauthors = Meira T, Leroy F, Buss EW, Oliva A, Park J, Siegelbaum SA | title = A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics | journal = Nature Communications | volume = 9 | issue = 1 | pages = 4163 | date = October 2018 | pmid = 30301899 | pmc = 6178349 | doi = 10.1038/s41467-018-06501-w | bibcode = 2018NatCo...9.4163M }}</ref>