View source for Hippocampus

{{Short description|Vertebrate brain region}}
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{{About|the section in the brain|the fish genus|Seahorse|the mythological creature|Hippocampus (mythology)|other uses}}
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{{Infobox Brain
 | Name            = Hippocampus
 | Latin           = hippocampus
 | Image           = Gray739-emphasizing-hippocampus.png
 | Caption         = Humans have two hippocampi, one in each [[cerebral hemisphere|hemisphere of the brain]]. They are located in the [[medial temporal lobe]] of the brain. In this lateral view of the [[human brain]], the [[frontal lobe]] is at the left, the [[occipital lobe]] at the right, and the [[temporal lobe|temporal]] and [[parietal lobe]]s have largely been removed to reveal one of the hippocampi underneath.
 | Image2          = 1511 The Limbic Lobe.jpg
 | Caption2        = Hippocampus (lowest pink region) as part of the [[limbic system]]
 | Width2          = 180px
 | IsPartOf        = [[Temporal lobe]]
 | Components      =
 | Artery          =
 | Vein            =
 }}

The '''hippocampus''' ({{plural form}}: '''hippocampi'''; via Latin from [[Ancient Greek|Greek]] {{lang|grc|ἱππόκαμπος}}, '[[seahorse]]'), also '''hippocampus proper''',  is a major component of the [[brain]] of [[human]]s and many other [[vertebrate]]s. In the [[human brain]] the hippocampus, the [[dentate gyrus]], and the [[subiculum]] are components of the [[hippocampal formation]] located in the [[limbic system]]. 
The hippocampus plays important roles in the [[Memory consolidation|consolidation]] of information from [[short-term memory]] to [[long-term memory]], and in [[spatial memory]] that enables [[Navigation#Navigation in spatial cognition|navigation]]. In humans and other primates the hippocampus is located in the [[archicortex]], one of the three regions of [[allocortex]], in each [[cerebral hemisphere|hemisphere]] with direct neural projections to,  and reciprocal indirect projections from the [[neocortex]]. The hippocampus, as the [[medial pallium]], is a structure found in all vertebrates.

In [[Alzheimer's disease]] (and other forms of [[dementia]]), the hippocampus is one of the first regions of the brain to be damaged; [[short-term memory|short-term memory loss]] and [[disorientation]] are included among the early symptoms. Damage to the hippocampus can also result from oxygen starvation ([[hypoxia (medical)|hypoxia]]), [[encephalitis]], or [[Temporal lobe epilepsy#Mesial temporal lobe epilepsy|medial temporal lobe epilepsy]]. People with extensive, bilateral hippocampal damage may experience [[anterograde amnesia]]: the inability to form and retain new [[memory|memories]].

Since different [[list of distinct cell types in the adult human body#Nervous system|neuronal cell types]] are neatly organized into layers in the hippocampus, it has frequently been used as a [[Scientific modelling|model system]] for studying [[neurophysiology]]. The form of [[synaptic plasticity|neural plasticity]] known as [[long-term potentiation]] (LTP) was initially discovered to occur in the hippocampus and has often been studied in this structure. LTP is widely believed to be one of the main neural mechanisms by which memories are stored in the brain.

Using [[rodent]]s as [[model organism]]s, the hippocampus has been studied extensively as part of a brain system responsible for spatial memory and navigation. Many [[neuron]]s in the [[Rattus norvegicus|rat]] and [[Mus musculus|mouse]] hippocampi respond as [[place cell]]s: that is, they fire bursts of [[action potential]]s when the animal passes through a specific part of its environment. 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]].

== Name ==
[[File:Hippocampus and seahorse cropped.JPG|thumb|right|The human hippocampus and [[Fornix of the brain|fornix]] (left) compared with a [[seahorse]] (right)<ref>Preparation by László Seress in 1980.</ref>]]

The earliest description of the ridge running along the floor of the [[Lateral ventricles#Inferior horn|inferior horn]] of the [[lateral ventricle]] comes from the Venetian anatomist [[Julius Caesar Aranzi]] (1587), who likened it first to a [[Bombyx mori|silkworm]] and then to a [[seahorse]] ([[Latin language|Latin]] ''hippocampus'', from [[Ancient Greek|Greek]] ἱππόκαμπος (latinised: ''ìppókampos'') from ἵππος (''ippos''), 'horse' + κάμπος (''kámpos''), 'sea monster').<ref name="Tatu">{{cite journal |vauthors=Tatu L, Bogousslavsky J |title=Beasts and Gods: Hippocampal quarrels before memory |journal=Rev Neurol (Paris) |volume=178 |issue=10 |pages=991–995 |date=December 2022 |pmid=35927101 |doi=10.1016/j.neurol.2022.03.022 |url=|doi-access=free }}</ref> The German anatomist [[Johann Georg Duvernoy]] (1729), the first to illustrate the structure, also wavered between "seahorse" and "silkworm". "Ram's horn" was proposed by the Danish anatomist [[Jacob B. Winslow|Jacob Winsløw]] in 1732; and a decade later his fellow Parisian, the surgeon de Garengeot, used ''cornu Ammonis'' – horn of [[Amun]],<ref name="Duv05">{{cite book | vauthors = Duvernoy HM | title = The Human Hippocampus | edition = 3rd | year = 2005 | publisher = Springer-Verlag | location = Berlin | isbn = 978-3-540-23191-2 | page = 1 | chapter = Introduction | chapter-url = https://books.google.com/books?id=5GkpPjk5z1IC&pg=PP1 | ref = refDuvernoy2005 | access-date = 2016-03-05 | archive-date = 2016-08-28 | archive-url = https://web.archive.org/web/20160828091605/https://books.google.com/books?id=5GkpPjk5z1IC&pg=PP1 | url-status = live }}</ref> after the ancient Egyptian god who was often represented as having a ram's head.<ref name="Neurologia2014">{{cite journal |last1=Iniesta |first1=I. |title=On the origin of Ammon's horn |journal=Neurología (English Edition) |date=October 2014 |volume=29 |issue=8 |pages=490–496 |doi=10.1016/j.nrleng.2012.03.024|pmid=22770681 }}</ref> ''Ammon'' is the Greek name for Amun.<ref name="autogenerated1">{{cite journal | vauthors = Pearce JM | title = Ammon's horn and the hippocampus | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 71 | issue = 3 | page = 351 | date = September 2001 | pmid = 11511709 | pmc = 1737533 | doi = 10.1136/jnnp.71.3.351 | ref = refPearce2001 | department = Historical Note }}</ref>

The head region of the hippocampus is enlarged, and presents two or three rounded elevations or foot-like digitations, and hence it was named the '''pes hippocampi''' (''pes'' meaning ''foot'').<ref>{{cite web|title=BrainInfo|url=http://braininfo.rprc.washington.edu/centraldirectory.aspx?ID=2283|website=braininfo.rprc.washington.edu}}</ref><ref name="Anand">{{cite journal |vauthors=Anand KS, Dhikav V |title=Hippocampus in health and disease: An overview |journal=Ann Indian Acad Neurol |volume=15 |issue=4 |pages=239–46 |date=October 2012 |pmid=23349586 |pmc=3548359 |doi=10.4103/0972-2327.104323 |doi-access=free |url=}}</ref> Later this part was described as ''pes hippocampi major'', with an adjacent bulge in the [[Lateral ventricles#Structure|occipital horn of the lateral ventricle]], described as ''pes hippocampi minor'' later renamed as the [[calcar avis]].<ref name="Duv05" /><ref>{{cite journal | vauthors = Owen CM, Howard A, Binder DK | title = Hippocampus minor, calcar avis, and the Huxley-Owen debate | journal = Neurosurgery | volume = 65 | issue = 6 | pages = 1098–1104; discussion 1104–1105 | date = December 2009 | pmid = 19934969 | doi = 10.1227/01.neu.0000359535.84445.0b | s2cid = 19663125 }}</ref> In 1786 [[Félix Vicq-d'Azyr]] published an authoritative description naming just the ''hippocampus'' but the term remained largely unused with no description of any function proposed until in the middle of the 20th century it was associated with memory.<ref name="Tatu" />

[[Johann Christoph Andreas Mayer|Mayer]] mistakenly used the term [[hippopotamus]] in 1779, and was followed by some other authors until [[Karl Friedrich Burdach]] resolved this error in 1829. In 1861 the hippocampus minor became the center of a dispute over [[human evolution]] between [[Thomas Henry Huxley]] and [[Richard Owen]], satirized as the [[Great Hippocampus Question]]. The term hippocampus minor fell from use in anatomy textbooks and was officially removed in the [[Nomina Anatomica]] of 1895.<ref>{{cite journal | vauthors = Gross CG | title = Hippocampus minor and man's place in nature: a case study in the social construction of neuroanatomy | journal = Hippocampus | volume = 3 | issue = 4 | pages = 403–415 | date = October 1993 | pmid = 8269033 | doi = 10.1002/hipo.450030403 | ref = refGross1993 | s2cid = 15172043 }}
</ref> The modern term for the structure is just the hippocampus, with the term ''cornu Ammonis'' (that is, 'Ammon's horn')  surviving in the names of the [[hippocampal subfields]] CA1–CA4.<ref name="Pang">{{cite journal | vauthors = Pang CC, Kiecker C, O'Brien JT, Noble W, Chang RC | title = Ammon's Horn 2 (CA2) of the Hippocampus: A Long-Known Region with a New Potential Role in Neurodegeneration | journal = The Neuroscientist | volume = 25 | issue = 2 | pages = 167–180 | date = April 2019 | pmid = 29865938 | doi = 10.1177/1073858418778747 | s2cid = 46929253 | url = https://kclpure.kcl.ac.uk/portal/en/publications/0547351a-ef50-44ac-b15d-e192706f446b }}</ref><ref name="Oxford">{{cite web |title=Search Results for ammon's horn |url=https://www.oxfordreference.com/search?q=ammon%27s+horn&searchBtn=Search&isQuickSearch=true |website=Oxford Reference |access-date=9 December 2021}}</ref><ref name="Colman">{{cite web | vauthors = Colman AM |title=dentate gyrus |url=https://www.oxfordreference.com/view/10.1093/acref/9780199657681.001.0001/acref-9780199657681-e-2184?rskey=auIwwd&result=10 |website=A Dictionary of Psychology |publisher=Oxford University Press |access-date=10 December 2021 |language=en |doi=10.1093/acref/9780199657681.001.0001 |date=21 May 2015|isbn=978-0-19-965768-1 }}</ref>

==In the limbic system==
[[File:Blausen 0614 LimbicSystem.png|thumb|Hippocampus in the [[limbic system]]]]

The hippocampus is one of the structures of the [[limbic lobe]], first described by [[Paul Broca|Broca]] in 1878, as the cortical areas that line the deep edge of the [[cerebral cortex]].<ref name="Purves2">{{cite book|title=Neuroscience|date=2012|publisher=Sinauer|isbn=978-0-87893-695-3 |edition=5th|location=Sunderland, MA|page=652| vauthors = Purves D }}</ref> The limbic lobe is the main component of the [[limbic system]].<ref name="Roxo">{{cite journal | vauthors = Roxo MR, Franceschini PR, Zubaran C, Kleber FD, Sander JW | title = The limbic system conception and its historical evolution | journal = TheScientificWorldJournal | volume = 11 | pages = 2428–2441 | year = 2011 | pmid = 22194673 | pmc = 3236374 | doi = 10.1100/2011/157150 | doi-access = free }}</ref> The [[cingulate gyrus]], and the [[parahippocampal gyrus]] are the two main parts of the described lobe, which had been largely associated with [[olfaction]].<ref name="Purves2"/> Many studies later culminating in work by [[Papez]], and [[Paul D. MacLean|MacLean]], the involvement of other interacting brain regions associated with [[emotion]] was recognized.<ref name="Roxo"/> The hippocampus is anatomically connected to parts of the brain that are involved with emotional behavior, including the [[Septal area#Connections|septal area]], the [[hypothalamus|hypothalamic]] [[mammillary bodies]], and the [[anterior nuclei of thalamus|anterior nuclear complex in the thalamus]]. MacLean proposed that the associated structures of the limbic lobe be included in what he termed as the ''limbic system''.<ref name="Roxo"/>

==Anatomy==
{{Main article |Hippocampus anatomy}}
[[File:Sobo 1909 639.png|thumb|right|220px| Cross-section of [[cerebral hemisphere]] showing structure and location of hippocampus]]
[[File:Brainmaps-macaque-hippocampus.jpg|thumb|220px| [[Coronal plane|Coronal]] section of the brain of a [[macaque]] monkey, showing hippocampal formation  (circled)]]
The hippocampus is a five centimeter long ridge of [[Gray matter|gray matter tissue]] within the [[parahippocampal gyrus]] that can only be seen when the gyrus is opened.<ref name="Fogwe2023">{{cite journal |last1=Fogwe |first1=Leslie A. |last2=Reddy |first2=Vamsi |last3=Mesfin |first3=Fassil B. |title=Neuroanatomy, Hippocampus |url=https://www.ncbi.nlm.nih.gov/books/NBK482171/#:~:text=The%20hippocampus%20has%20three%20distinct,and%20entorhinal%20and%20other%20cortices. |website=StatPearls |publisher=StatPearls Publishing |date=2025|pmid=29489273 }}</ref><ref name="Purves">{{cite book|title=Neuroscience|date=2011|publisher=Sinauer|isbn=978-0-87893-695-3 |edition=5th|location=Sunderland, MA|pages=730–735| vauthors = Purves D }}</ref> The hippocampus is an inward fold of three-layered  [[archicortex]] (one of three regions of the [[allocortex]]) into the [[Temporal lobe#Medial temporal lobe|medial temporal lobe]] of the brain, where it elevates into the floor of each [[lateral ventricle]] [[Lateral ventricle#Inferior horn of lateral ventricle|inferior horn]].<ref name="Morris and Amaral2024">{{cite book |last1=Morris |first1=Richard |last2=Amaral |first2=David |title=The Hippocampus Book |date=2024 |pages= 49–50|publisher=Oxford University Press, Incorporated |location=Oxford |isbn=978-0-19-006532-4 |edition=2nd}}</ref><ref name="Creutzfeldt">{{cite journal |last1=Creutzfeldt |first1=O.D. |title=The allocortex and limbic system |journal=Cortex Cerebri: Performance, Structural and Functional Organisation of the Cortex |date=27 April 1995 |pages=486–540 |doi=10.1093/acprof:oso/9780198523246.003.0009|isbn=978-0-19-852324-6 }}</ref><ref name="Anderson"/><ref>{{cite journal | vauthors = Bachevalier J | title = Nonhuman primate models of hippocampal development and dysfunction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 52 | pages = 26210–26216 | date = December 2019 | pmid = 31871159 | pmc = 6936345 | doi = 10.1073/pnas.1902278116 | doi-access = free | bibcode = 2019PNAS..11626210B }}</ref> The hippocampus stretches along its anterior-posterior axis, from the [[amygdala]] to the [[Corpus callosum#Splenium|splenium of the corpus callosum]], with the head, body, and tail regions as subdivisions of this axis.<ref name="Sun">{{cite journal |vauthors=Sun F, Shuai Y, Wang J, Yan J, Lin B, Li X, Zhao Z |title=Hippocampal gray matter volume alterations in patients with first-episode and recurrent major depressive disorder and their associations with gene profiles |journal=BMC Psychiatry |volume=25 |issue=1 |article-number=134 |date=February 2025 |pmid=39955494 |doi=10.1186/s12888-025-06562-4 |doi-access=free |pmc=11829352 |url=}}</ref><ref name="Fogwe2023"/> The [[dentate gyrus]], CA subfields, [[Fimbria (neuroanatomy)|fimbria]], and [[subiculum]] are divisions across the short axis, the proximal-distal axis.<ref name="Sun"/>

The [[hippocampal formation]] refers to the hippocampus, and its related adjoining parts to include the dentate gyrus, the subiculum, the [[presubiculum]], [[parasubiculum]], and the [[entorhinal cortex]].<ref name="Morris and Amaral2024"/> Sometimes the subiculum, presubiculum, and parasubiculum are grouped together as the ''subicular complex'', but the regions are neuroanatomically distinct. Some sources may only include the hippocampus, dentate gyrus, and subiculum, being regions of the hippocampal three-layered archicortex.<ref name="Morris and Amaral2024"/> But the six regions are linked together serially by almost unidirectional neural pathways.<ref name="Morris and Amaral2024"/> Other sources include the [[indusium griseum]], [[gyrus fasciolaris]], the [[medial longitudinal stria|medial]] and [[longitudinal striae]], and [[uncus]], and exclude subicular regions.<ref name="Singh">{{cite book |last1=Singh |first1=Vishram |title=Textbook. of Anatomy Vol III |date=2017 |publisher=Elsevier |isbn=978-81-312-3727-4 |page=402}}</ref><ref name="Chauhan">{{cite journal |last1=Chauhan |first1=Pradip |last2=Jethwa |first2=Kinjal |last3=Rathawa |first3=Ashish |last4=Chauhan |first4=Girish |last5=Mehra |first5=Simmi |title=The Anatomy of the Hippocampus |url=https://www.ncbi.nlm.nih.gov/books/NBK575732/ |website=Cerebral Ischemia |publisher=Exon Publications |access-date=19 March 2025 |date=2021|pmid=34905307 }}</ref> The neural layout and pathways within the hippocampal formation are very similar in all mammals.<ref name="Anderson">{{cite book|vauthors= Anderson P, Morris R, Amaral, Bliss T, O'Keefe J|veditors= Anderson P, Morris R, Amaral, Bliss T, O'Keefe J|title= The hippocampus book|edition= first|year= 2007|publisher= Oxford University Press|location= New York|isbn= 978-0-19-510027-3|pages=3–77 |chapter = The hippocampal formation|chapter-url= https://books.google.com/books?id=zg6oyF1DziQC&pg=PA3|access-date= 2016-12-15|archive-date= 2020-03-15|archive-url= https://web.archive.org/web/20200315125212/https://books.google.com/books?id=zg6oyF1DziQC&pg=PA3|url-status= live}}</ref>

The hippocampus has a generally similar appearance across the range of mammals, from [[Monotreme|egg-laying mammals]] such as the [[echidna]], to humans and other [[primate]]s.<ref>{{cite book | ref=refWest1990 | vauthors = West MJ | title = Stereological studies of the hippocampus: a comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men | volume = 83 | pages = 13–36 | year = 1990 | pmid = 2203095 | doi = 10.1016/S0079-6123(08)61238-8 | isbn = 978-0-444-81149-3 | series = Progress in Brain Research | chapter = Chapter 2 Stereological studies of the hippocampus: A comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men }}</ref> The hippocampal-size-to-body-size ratio broadly increases, being about twice as large for primates as for the echidna. It does not, however, increase at anywhere close to the rate of the [[neocortex]]-to-body-size ratio. Therefore, the hippocampus takes up a much larger fraction of the cortical mantle in rodents than in primates. In adult humans the volume of the hippocampus on each side of the brain is about 3.0 to 3.5&nbsp;cm<sup>3</sup> as compared to 320 to 420&nbsp;cm<sup>3</sup> for the volume of the neocortex.<ref>* {{cite journal | vauthors = Suzuki M, Hagino H, Nohara S, Zhou SY, Kawasaki Y, Takahashi T, Matsui M, Seto H, Ono T, Kurachi M | title = Male-specific volume expansion of the human hippocampus during adolescence | journal = Cerebral Cortex | volume = 15 | issue = 2 | pages = 187–193 | date = February 2005 | pmid = 15238436 | doi = 10.1093/cercor/bhh121 | ref = refSuzuki2005 | doi-access = free }}</ref> There is also a general relationship between the size of the hippocampus and spatial memory. When comparisons are made between similar species, those that have a greater capacity for spatial memory tend to have larger hippocampal volumes.<ref name="Jacobs2003">{{cite journal | vauthors = Jacobs LF | title = The evolution of the cognitive map | journal = Brain, Behavior and Evolution | volume = 62 | issue = 2 | pages = 128–139 | year = 2003 | pmid = 12937351 | doi = 10.1159/000072443 | ref = refJacobs2003 | s2cid = 16102408 }}</ref>

==Neuroanatomy==

The hippocampus, and dentate gyrus that is folded into the hippocampal archicortex have the shape of a curved, rolled-up tube. The curve of the hippocampus  (known as ''cornu Ammonis'') uses the initial letters ''CA'' to name the [[Hippocampal subfields|hippocampal subfields CA1-CA4]]. CA4 is in fact the polymorphic layer or [[hilus]] of the dentate gyrus, but CA4 is still sometimes in use to describe the part of CA3 that inserts between the dentate gyrus regions or ''blades''.<ref name="Morris and Amaral2024"/><ref name="Chen">{{cite journal |vauthors=Chen HJ, Qiu J, Qi Y, Fu L, Fu Q, Wu W, Dai G, Chen F |title=Hippocampal subfield morphology in regular hemodialysis patients |journal=Nephrol Dial Transplant |volume=38 |issue=4 |pages=992–1001 |date=March 2023 |pmid=36124763 |pmc=10064839 |doi=10.1093/ndt/gfac263 |url=}}</ref>

It can be distinguished as an area where the cortex narrows into a single layer of densely packed [[pyramidal cell|pyramidal neurons]], which curl into a tight U shape. One edge of the "U" is CA4, the hilus of the dentate gyrus. This is embedded into the backward-facing, flexed dentate gyrus. In [[human]]s the hippocampus is described as having an [[anterior and posterior]] part; in other primates they are termed [[Anatomical terms of location#Rostral, cranial, and caudal|rostral and caudal]], and in [[rodent]] literature they are the  [[Anatomical terms of location#Dorsal and ventral|ventral and dorsal]] part.<ref name="Dalton"/> Both parts are of similar composition but belong to different [[neural circuit]]s.<ref>{{cite journal | vauthors = Moser MB, Moser EI | title = Functional differentiation in the hippocampus | journal = Hippocampus | volume = 8 | issue = 6 | pages = 608–619 | year = 1998 | pmid = 9882018 | doi = 10.1002/(SICI)1098-1063(1998)8:6<608::AID-HIPO3>3.0.CO;2-7 | ref = refMoser1998 | s2cid = 32384692 }}</ref> The dentate gyrus combined with other hippocampal regions form a banana-like structure, with the two hippocampi joined at the stems by the [[Fornix (neuroanatomy)#Commissure|commissure of fornix]] (also called the hippocampal commissure).<ref name="Anderson"/><ref name="Amaral">{{cite book |vauthors=Amaral DG, Scharfman HE, Lavenex P |chapter=The dentate gyrus: Fundamental neuroanatomical organization (Dentate gyrus for dummies) |title=The Dentate Gyrus: A Comprehensive Guide to Structure, Function, and Clinical Implications |series=Progress in Brain Research |volume=163 |pages=3–22 |date=2007 |pmid=17765709 |pmc=2492885 |doi=10.1016/S0079-6123(07)63001-5 |isbn=978-0-444-53015-8 |chapter-url=}}</ref> In primates, the part of the hippocampus at the bottom, near the base of the [[temporal lobe]], is much broader than the part at the top. This means that in cross-section the hippocampus can show a number of different shapes, depending on the angle and location of the cut.<ref>{{cite book | vauthors = Duvernoy H, Cattin F, Risold PY | chapter = Vascularization | pages = 69–105 | veditors = Duvernoy HM, Cattin F, Risold PY | title = The human hippocampus: functional anatomy, vascularization and serial sections with MRI. | location = Berlin | publisher = Springer | date = June 2005 | isbn = 978-3-642-33603-4 | doi = 10.1007/978-3-642-33603-4_5 }}</ref>

In a cross-section of the hippocampus, including the dentate gyrus, several layers will be shown. The dentate gyrus has three layers of cells – the outer ''molecular layer'', the middle ''granular layer'', and the inner ''polymorphic layer'' also known as the ''hilus''.<ref name="Jinde">{{cite journal |vauthors=Jinde S, Zsiros V, Nakazawa K |title=Hilar mossy cell circuitry controlling dentate granule cell excitability |journal=Front Neural Circuits |volume=7 |issue= |page=14 |date=2013 |pmid=23407806 |pmc=3569840 |doi=10.3389/fncir.2013.00014 |doi-access=free |url=}}</ref> The CA3 subfield has the following cell layers known as strata: lacunosum-moleculare, radiatum, lucidum, pyramidal, and oriens. CA2 and CA1 also have these layers except the [[stratum lucidum of hippocampus|lucidum stratum]].<ref>{{cite journal | vauthors = Murakami G, Tsurugizawa T, Hatanaka Y, Komatsuzaki Y, Tanabe N, Mukai H, Hojo Y, Kominami S, Yamazaki T, Kimoto T, Kawato S | title = Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus | journal = Biochemical and Biophysical Research Communications | volume = 351 | issue = 2 | pages = 553–558 | date = December 2006 | pmid = 17070772 | doi = 10.1016/j.bbrc.2006.10.066 | bibcode = 2006BBRC..351..553M | quote = CA1 neurons consist of four regions, i.e., the stratum oriens, the cell body, the stratum radiatum, and the stratum lacunosum-moleculare }}</ref>

The input to the hippocampus (from varying cortical and subcortical structures) comes from the [[entorhinal cortex]] via the [[perforant path]].<ref name = "Witter_2011" >{{cite journal | vauthors = Witter M | title = Entorhinal cortex | journal = Scholarpedia | date = October 2011 | volume = 6 | issue = 10 | page = 4380 | doi = 10.4249/scholarpedia.4380 | doi-access = free | bibcode = 2011SchpJ...6.4380W }}</ref> The entorhinal cortex (EC) is strongly and reciprocally connected with many cortical and subcortical structures as well as with the brainstem. Different [[thalamic nuclei]], (from the anterior and midline groups), the [[medial septal nucleus]],<ref name="Takeuchi_2021">{{cite journal | vauthors = Takeuchi Y, Nagy AJ, Barcsai L, Li Q, Ohsawa M, Mizuseki K, Berényi A | title = The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies | journal = Frontiers in Neural Circuits | volume = 15 | issue = | article-number = 701080 | date = 2021 | pmid = 34305537 | pmc = 8297467 | doi = 10.3389/fncir.2021.701080 | doi-access = free | url = }}</ref> the [[supramammillary nucleus]] of the hypothalamus, and the [[raphe nuclei]] and [[locus coeruleus]] of the [[brainstem]] all send axons to the EC, so that it serves as the interface between the [[neocortex]] and the other connections, and the hippocampus.<ref name = "Witter_2011" />

The EC is located in the [[parahippocampal gyrus]], a cortical region adjacent to the hippocampus.<ref name=Eichenbaum2007 /> This gyrus conceals the hippocampus. The parahippocampal gyrus is adjacent to the [[perirhinal cortex]], which plays an important role in the [[cognitive neuroscience of visual object recognition|visual recognition]] of complex objects. There is also substantial evidence that it makes a contribution to memory, which can be distinguished from the contribution of the hippocampus. It is apparent that complete [[amnesia]] occurs only when both the hippocampus and the parahippocampus are damaged.<ref name=Eichenbaum2007>{{cite journal | vauthors = Eichenbaum H, Yonelinas AP, Ranganath C | title = The medial temporal lobe and recognition memory | journal = Annual Review of Neuroscience | volume = 30 | pages = 123–152 | year = 2007 | pmid = 17417939 | pmc = 2064941 | doi = 10.1146/annurev.neuro.30.051606.094328 }}
</ref>

===Circuitry===
[[File:CajalHippocampus (modified).png|thumb|280px|left| Basic circuit of the hippocampus, as drawn by [[Santiago Ramón y Cajal|Ramón y Cajal]]. DG: [[dentate gyrus]]. Sub: [[subiculum]]. EC: [[entorhinal cortex]]]]
The major input to the hippocampus is through the entorhinal cortex (EC), whereas its major output is via [[Hippocampal subfields#CA1|CA1]] to the subiculum.<ref name="Kandel2012">{{Cite book | ref=refKandel2012 | title = Principles of Neural Science | vauthors = Kandel ER, Schwartz JH, Jessell TM, Siegelbaum SA, Hudspeth AJ | publisher = McGraw-Hill Medical | year = 2012 | isbn = 978-0-07-139011-8 | edition = 5th | location = New York | pages = 1490–1491 | oclc = 820110349}}</ref> Information reaches CA1 via two main pathways, direct and indirect. Axons from the EC that originate in layer III are the origin of the direct perforant pathway and form synapses on the very distal [[apical dendrite]]s of CA1 neurons. Conversely, axons originating from layer II are the origin of the indirect pathway, and information reaches CA1 via the [[trisynaptic circuit]]. In the initial part of this pathway, the axons project through the perforant pathway to the granule cells of the dentate gyrus (first synapse). From then, the information follows via the [[Mossy fiber (hippocampus)|mossy cell fibers]] to [[Hippocampal subfields#CA3|CA3]] (second synapse). From there, CA3 axons called [[Schaffer collaterals]] leave the deep part of the [[soma (biology)|cell body]] and loop up to the apical dendrites and then extend to CA1 (third synapse).<ref name="Kandel2012" /> Axons from CA1 then project back to the entorhinal cortex, completing the circuit.<ref>{{cite book | vauthors = Purves D |title=Neuroscience |date=2011 |publisher=Sinauer |location=Sunderland, Mass. |isbn=978-0-87893-695-3 |page=171 |edition=5th}}</ref>

[[Basket cell]]s in CA3 receive [[excitatory postsynaptic potential|excitatory]] input from the pyramidal cells and then give an [[inhibitory postsynaptic potential|inhibitory]] feedback to the pyramidal cells. This ''recurrent inhibition'' is a simple feedback circuit that can dampen excitatory responses in the hippocampus. The pyramidal cells give a ''recurrent excitation'' which is an important mechanism found in some memory processing microcircuits.<ref name="UTH">{{cite book | vauthors = Byrne JH | title = Introduction to Neurons and Neuronal Networks | chapter = Section 1, Intro Chapter | series = Neuroscience Online: An Electronic Textbook for the Neurosciences | publisher = Department of Neurobiology and Anatomy – The University of Texas Medical School at Houston | chapter-url = http://neuroscience.uth.tmc.edu/s1/introduction.html |archive-url=https://web.archive.org/web/20131203010009/http://neuroscience.uth.tmc.edu/s1/introduction.html|archive-date=2013-12-03}}</ref>

Several other connections play important roles in hippocampal function.<ref name="Anderson" /> Beyond the output to the EC, additional output pathways go to other cortical areas including the [[prefrontal cortex]]. A major output goes via the [[fornix (neuroanatomy)|fornix]] to the [[Septal area|lateral septal area]] and to the [[mammillary body]] of the hypothalamus (which the fornix interconnects with the hippocampus).<ref name=Purves /> The hippocampus receives modulatory input from the [[serotonin]], [[norepinephrine]], and [[dopamine]] systems, and from the [[nucleus reuniens]] of the [[thalamus]] to field CA1. A very important projection comes from the medial septal nucleus, which sends [[cholinergic]], and [[gamma amino butyric acid]] (GABA) stimulating fibers (GABAergic fibers) to all parts of the hippocampus. The inputs from the medial septal nucleus play a key role in controlling the physiological state of the hippocampus; destruction of this nucleus abolishes the hippocampal [[theta rhythm]] and severely impairs certain types of memory.<ref>{{cite journal | vauthors = Winson J | title = Loss of hippocampal theta rhythm results in spatial memory deficit in the rat | journal = Science | volume = 201 | issue = 4351 | pages = 160–163 | date = July 1978 | pmid = 663646 | doi = 10.1126/science.663646 | ref = refWinson1978 | bibcode = 1978Sci...201..160W }}
</ref>

===Subfields===
[[File:Hippocampus coronal section176157.fig.004.jpg|thumb|260px| Hippocampal subregions, and [[Hippocampal subfields|subfields]]]]
[[File:Golgi Hippocampus.jpg|thumb|260px| Drawing by Italian pathologist [[Camillo Golgi]] of a hippocampus [[Staining|stained]] using [[silver nitrate]]]]
[[Hippocampal subfields]], and subregions, head, body, and tail, are functionally and anatomically differentiated, and connect differently to other brain regions.<ref name="Xiao2023">{{cite journal |vauthors=Xiao Y, Hu Y, Huang K |title=Atrophy of hippocampal subfields relates to memory decline during the pathological progression of Alzheimer's disease |journal=Front Aging Neurosci |volume=15 |issue= |article-number=1287122 |date=2023 |pmid=38149170 |pmc=10749921 |doi=10.3389/fnagi.2023.1287122 |doi-access=free |url=}}</ref><ref name="Canada2020">{{cite journal |vauthors=Canada KL, Botdorf M, Riggins T |title=Longitudinal development of hippocampal subregions from early- to mid-childhood |journal=Hippocampus |volume=30 |issue=10 |pages=1098–1111 |date=October 2020 |pmid=32497411 |pmc=8500647 |doi=10.1002/hipo.23218 |url=}}</ref> Their cells are morphologically different.<ref name="Ezama">{{cite journal |vauthors=Ezama L, Hernández-Cabrera JA, Seoane S, Pereda E, Janssen N |title=Functional connectivity of the hippocampus and its subfields in resting-state networks |journal=Eur J Neurosci |volume=53 |issue=10 |pages=3378–3393 |date=May 2021 |pmid=33786931 |pmc=8252772 |doi=10.1111/ejn.15213 |url=}}</ref> They also have different levels of vulnerability to disease.<ref name="Xiao2023"/>

In humans the head of the hippocampus is termed the anterior hippocampus, the body is the intermediate hippocampus, and the tail the posterior hippocampus. The subregions all serve different functions, project with different [[neural pathway]]s, and have varying numbers of [[place cell]]s.<ref name=Fanselow2010>{{cite journal | vauthors = Fanselow MS, Dong HW | title = Are the dorsal and ventral hippocampus functionally distinct structures? | journal = Neuron | volume = 65 | issue = 1 | pages = 7–19 | date = January 2010 | pmid = 20152109 | pmc = 2822727 | doi = 10.1016/j.neuron.2009.11.031 | ref = refFanselow2010 }}</ref> (In other primates the terms used are rostral and caudal, and in rodents they are termed ventral and dorsal).<ref name="Dalton">{{cite journal |vauthors=Dalton MA, D'Souza A, Lv J, Calamante F |title=New insights into anatomical connectivity along the anterior-posterior axis of the human hippocampus using in vivo quantitative fibre tracking |journal=eLife |volume=11 |issue= |date=November 2022 |article-number=e76143 |pmid=36345716 |pmc=9643002 |doi=10.7554/eLife.76143 |doi-access=free |url=}}</ref> The posterior hippocampus serves for spatial memory, [[verbal memory]], and learning of conceptual information. Using the [[radial arm maze]] in rats, lesions in the dorsal hippocampus were shown to cause spatial memory impairment. Its projecting pathways include the [[medial septal nucleus]], and [[supramammillary nucleus]].<ref>{{cite journal | vauthors = Pothuizen HH, Zhang WN, Jongen-Rêlo AL, Feldon J, Yee BK | title = Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory | journal = The European Journal of Neuroscience | volume = 19 | issue = 3 | pages = 705–712 | date = February 2004 | pmid = 14984421 | doi = 10.1111/j.0953-816X.2004.03170.x | ref = refPothuizen2004 | s2cid = 33385275 }}</ref> In the rat the dorsal hippocampus also has more place cells than both the ventral and intermediate hippocampal regions.<ref>{{cite journal | vauthors = Jung MW, Wiener SI, McNaughton BL | title = Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat | journal = The Journal of Neuroscience | volume = 14 | issue = 12 | pages = 7347–7356 | date = December 1994 | pmid = 7996180 | pmc = 6576902 | doi = 10.1523/JNEUROSCI.14-12-07347.1994 | ref = refJung1994 }}</ref>

In the early 20th century, the widely held view was that [[olfaction]] was a major hippocampal function.<ref name="Morris and Amaral2024a">{{cite book |last1=Morris |first1=Richard |last2=Amaral |first2=David |title=The Hippocampus Book |date=2024 |pages= 8–9|publisher=Oxford University Press, Incorporated |location=Oxford |isbn=978-0-19-006532-4 |edition=2nd}}</ref> This view was argued against, pointing out that the hippocampus was present in some animals such as [[dolphin]]s and [[whale]]s, that did not have a sense of smell; and further that lesions in the temporal lobe in dogs had been shown to have no effect on their sense of smell.<ref name="Morris and Amaral2024a"/> These arguments were concluded in 1947 and held for a few more decades. In 1984, and 1987, studies in the rat showed that the entorhinal cortex receives substantial input from the olfactory bulb, with part of the EC being directly innervated by the [[lateral olfactory tract]].<ref name="Morris and Amaral2024a"/> Secondary inputs to the EC were also shown to include some from the periamygdaloid and piriform cortices, and CA1 in the ventral hippocampus was shown to sends axons to the main olfactory bulb.<ref name="Van Groen 1990">{{cite journal | vauthors = van Groen T, Wyss JM | title = Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections | journal = The Journal of Comparative Neurology | volume = 302 | issue = 3 | pages = 515–528 | date = December 1990 | pmid = 1702115 | doi = 10.1002/cne.903020308 | s2cid = 7175722 }}</ref><ref name="Morris and Amaral2024a"/> It is evident that the hippocampus does have an involvement in memory for odors.<ref>{{cite book | vauthors = Eichenbaum H, Otto TA, Wible CG, Piper JM | veditors = Davis JL, Eichenbaum H | title=Olfaction | year=1991 | chapter=Ch 7. Building a model of the hippocampus in olfaction and memory | publisher=MIT Press | isbn=978-0-262-04124-9 |ref=refEichenbaum1991}}</ref><ref name="Eichenbaum">{{cite book |vauthors=Eichenbaum H, Cohen NJ| title = Memory, Amnesia, and the Hippocampal System | year =1993 | publisher =MIT Press | ref = refEichenbaum1993 }}</ref>

The intermediate hippocampus has overlapping characteristics with both the ventral and dorsal hippocampus.<ref name=Fanselow2010/><ref>{{Cite journal |last1=Bast |first1=Tobias |last2=Wilson |first2=Iain A. |last3=Witter |first3=Menno P. |last4=Morris |first4=Richard G. M. |date=2009-04-21 |title=From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus |journal=PLOS Biology |language=en |volume=7 |issue=4 |article-number=e1000089 |doi=10.1371/journal.pbio.1000089 |doi-access=free |issn=1545-7885 |pmc=2671558 |pmid=19385719}}</ref> Studies in 2002, showed that alterations to the ventral hippocampus reduced the amount of information sent to the amygdala by the dorsal and ventral hippocampus, consequently altering fear conditioning in rats.<ref>{{cite journal | vauthors = Anagnostaras SG, Gale GD, Fanselow MS | title = The hippocampus and Pavlovian fear conditioning: reply to Bast et al | journal = Hippocampus | volume = 12 | issue = 4 | pages = 561–565 | year = 2002 | pmid = 12201641 | doi = 10.1002/hipo.10071 | url = http://homepage.mac.com/sanagnos/19bastreply2002.pdf | ref = refAnagnostaras2002 | s2cid = 733197 | archive-url = https://web.archive.org/web/20050216104718/http://homepage.mac.com/sanagnos/19bastreply2002.pdf | archive-date = 2005-02-16 }}</ref> In 2007, studies using [[anterograde tracing]] methods, located the moderate projections to two primary olfactory cortical areas and prelimbic areas of the [[Prefrontal cortex#Interconnections|medial prefrontal cortex]]. This region has the smallest number of place cells. The ventral hippocampus has been particularly linked to fear conditioning and affective processes.<ref>{{cite journal | vauthors = Cenquizca LA, Swanson LW | title = Spatial organization of direct hippocampal field CA1 axonal projections to the rest of the cerebral cortex | journal = Brain Research Reviews | volume = 56 | issue = 1 | pages = 1–26 | date = November 2007 | pmid = 17559940 | pmc = 2171036 | doi = 10.1016/j.brainresrev.2007.05.002 | ref = refCenquizca2007 }}</ref><ref>{{Cite journal |last1=Bannerman |first1=D. M |last2=Rawlins |first2=J. N. P |last3=McHugh |first3=S. B |last4=Deacon |first4=R. M. J |last5=Yee |first5=B. K |last6=Bast |first6=T |last7=Zhang |first7=W. -N |last8=Pothuizen |first8=H. H. J |last9=Feldon |first9=J |date=2004-05-01 |title=Regional dissociations within the hippocampus—memory and anxiety |url=https://www.sciencedirect.com/science/article/pii/S0149763404000314 |journal=Neuroscience & Biobehavioral Reviews |series=Festschrift in Honour of Jeffrey Gray - Issue 1: Anxiety and Neuroticism |volume=28 |issue=3 |pages=273–283 |doi=10.1016/j.neubiorev.2004.03.004 |pmid=15225971 |issn=0149-7634|url-access=subscription }}</ref> 

== 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 |article-number=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 |url-access=subscription }}</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 |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|page=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|page=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 = | article-number = 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 | article-number = 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 [[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 rhesus 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 | article-number = 4163 | date = October 2018 | pmid = 30301899 | pmc = 6178349 | doi = 10.1038/s41467-018-06501-w | bibcode = 2018NatCo...9.4163M }}</ref>

== Physiology ==
[[File:Rat-hippocampal-activity-modes.png|thumb|300px| Examples of rat hippocampal [[EEG]] and CA1 neural activity in the [[Theta wave|theta]] (awake/behaving) and LIA ([[slow-wave sleep]]) modes. Each plot shows 20 seconds of data, with a hippocampal EEG trace at the top, spike rasters from 40 simultaneously recorded CA1 [[pyramidal cells]] in the middle (each raster line represents a different cell), and a plot of running speed at the bottom. The top plot represents a time period during which the rat was actively searching for scattered food pellets. For the bottom plot the rat was asleep.]]

The hippocampus shows two major modes of activity, each associated with a distinct pattern of [[neural population]] activity and waves of electrical activity as measured by an [[electroencephalogram]] (EEG). These modes are named after the EEG patterns associated with them: [[theta waves|theta]] and [[large irregular activity]] (LIA). The main characteristics described below are for the rat, which is the animal most extensively studied.<ref name="Buzsaki2006"/>

The theta mode appears during states of active, alert behavior (especially locomotion), and also during [[Rapid eye movement sleep|REM sleep]] (dreaming).<ref name=Buzsaki1990>{{cite book | ref=refBuzsaki1990 | vauthors = Buzsáki G, Chen LS, Gage FH | title = Spatial organization of physiological activity in the hippocampal region: relevance to memory formation | volume = 83 | pages = 257–268 | year = 1990 | pmid = 2203100 | doi = 10.1016/S0079-6123(08)61255-8 | isbn = 978-0-444-81149-3 | series = Progress in Brain Research | chapter = Chapter 19 Chapter Spatial organization of physiological activity in the hippocampal region: Relevance to memory formation }}</ref> In the theta mode, the EEG is dominated by large regular waves with a [[frequency range]] of 6 to 9 [[Hertz|Hz]], and the main groups of hippocampal neurons ([[pyramidal cell]]s and [[granule cell]]s) show sparse population activity, which means that in any short time interval, the great majority of cells are silent, while the small remaining fraction fire at relatively high rates, up to 50 spikes in one second for the most active of them.<ref>{{Cite book| vauthors = Squire LR | chapter = Learning and Memory: Brain Systems | veditors = Ghosh A, Berg D, Bloom FE, Squire L, Spitzer NC, du Lac S |title=Fundamental Neuroscience|date=17 December 2012|isbn=978-0-12-385871-9|edition=4th |publisher=Elsevier/Academic Press |location=Amsterdam|page=1038|oclc=830351091}}</ref><ref name="Colgin_2016">{{cite journal | vauthors = Colgin LL | title = Rhythms of the hippocampal network | journal = Nature Reviews. Neuroscience | volume = 17 | issue = 4 | pages = 239–249 | date = April 2016 | pmid = 26961163 | pmc = 4890574 | doi = 10.1038/nrn.2016.21 }}</ref> An active cell typically stays active for half a second to a few seconds. As the rat behaves, the active cells fall silent and new cells become active, but the overall percentage of active cells remains more or less constant. In many situations, cell activity is determined largely by the spatial location of the animal,<ref name="Radvansky_2021">{{cite journal | vauthors = Radvansky BA, Oh JY, Climer JR, Dombeck DA | title = Behavior determines the hippocampal spatial mapping of a multisensory environment | journal = Cell Reports | volume = 36 | issue = 5 | article-number = 109444 | date = August 2021 | pmid = 34293330 | pmc = 8382043 | doi = 10.1016/j.celrep.2021.109444 }}</ref> but other behavioral variables also clearly influence it.

The LIA mode appears during [[slow-wave sleep]] (non-dreaming), and also during states of waking immobility such as resting or eating.<ref name=Buzsaki1990 /> In the LIA mode, the EEG is dominated by sharp waves that are randomly timed large deflections of the EEG signal lasting for 25–50 milliseconds. Sharp waves are frequently generated in sets, with sets containing up to 5 or more individual sharp waves and lasting up to 500 ms. The spiking activity of neurons within the hippocampus is highly correlated with sharp wave activity. Most neurons decrease their firing rate between sharp waves; however, during a sharp wave, there is a dramatic increase in firing rate in up to 10% of the hippocampal population.<ref name="Buzsáki_2015">{{cite journal | vauthors = Buzsáki G | title = Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning | journal = Hippocampus | volume = 25 | issue = 10 | pages = 1073–188 | date = October 2015 | pmid = 26135716 | pmc = 4648295 | doi = 10.1002/hipo.22488 }}</ref>

These two hippocampal activity modes can be seen in primates as well as rats, with the exception that it has been difficult to see robust theta rhythmicity in the primate hippocampus. There are, however, qualitatively similar sharp waves and similar state-dependent changes in neural population activity.<ref name=Skaggs2007>{{cite journal | vauthors = Skaggs WE, McNaughton BL, Permenter M, Archibeque M, Vogt J, Amaral DG, Barnes CA | title = EEG sharp waves and sparse ensemble unit activity in the macaque hippocampus | journal = Journal of Neurophysiology | volume = 98 | issue = 2 | pages = 898–910 | date = August 2007 | pmid = 17522177 | doi = 10.1152/jn.00401.2007 | ref = refSkaggs2007 | s2cid = 941428 }}</ref>

=== Hippocampal theta rhythm ===
{{Main|Theta wave}}
[[File:eeg theta.svg|thumb|Example of a one-second EEG theta wave|350px|right]]
The underlying currents producing the [[theta wave]] are generated mainly by densely packed neural layers of the entorhinal cortex, CA3, and the dendrites of pyramidal cells. The theta wave is one of the largest signals seen on EEG, and is known as the hippocampal theta rhythm.<ref name=Buzsaki2002>{{cite journal | vauthors = Buzsáki G | title = Theta oscillations in the hippocampus | journal = Neuron | volume = 33 | issue = 3 | pages = 325–340 | date = January 2002 | pmid = 11832222 | doi = 10.1016/S0896-6273(02)00586-X | ref = refBuzsaki2002 | s2cid = 15410690 | doi-access = free }}</ref> In some situations the EEG is dominated by regular waves at 3 to 10&nbsp;Hz, often continuing for many seconds. These reflect subthreshold [[membrane potential]]s and strongly modulate the spiking of hippocampal neurons and synchronize across the hippocampus in a travelling wave pattern.<ref>{{cite journal | vauthors = Lubenov EV, Siapas AG | title = Hippocampal theta oscillations are travelling waves | journal = Nature | volume = 459 | issue = 7246 | pages = 534–539 | date = May 2009 | pmid = 19489117 | doi = 10.1038/nature08010 | url = https://authors.library.caltech.edu/14755/2/Lubenov2009p4508Nature_supp.pdf | ref = refLubenov2009 | access-date = 2019-07-13 | url-status = live | s2cid = 4429491 | bibcode = 2009Natur.459..534L | archive-url = https://web.archive.org/web/20180723181835/https://authors.library.caltech.edu/14755/2/Lubenov2009p4508Nature_supp.pdf | archive-date = 2018-07-23 }}</ref> The [[trisynaptic circuit]] is a relay of [[neurotransmission]] in the hippocampus that interacts with many brain regions. From [[animal testing on rodents|rodent studies]] it has been proposed that the trisynaptic circuit generates the hippocampal theta rhythm.<ref>{{cite journal | vauthors = Komisaruk BR | title = Synchrony between limbic system theta activity and rhythmical behavior in rats | journal = Journal of Comparative and Physiological Psychology | volume = 70 | issue = 3 | pages = 482–492 | date = March 1970 | pmid = 5418472 | doi = 10.1037/h0028709 | author1-link = Barry Komisaruk }}</ref>

Theta rhythmicity previously clearly shown in rabbits and rodents has also been shown in humans.<ref>{{cite journal | vauthors = Cantero JL, Atienza M, Stickgold R, Kahana MJ, Madsen JR, Kocsis B | title = Sleep-dependent theta oscillations in the human hippocampus and neocortex | journal = The Journal of Neuroscience | volume = 23 | issue = 34 | pages = 10897–10903 | date = November 2003 | pmid = 14645485 | pmc = 6740994 | doi = 10.1523/JNEUROSCI.23-34-10897.2003 | ref = refCantero2003 }}</ref> In [[laboratory rat|rats]] (the animals that have been the most extensively studied), theta is seen mainly in two conditions: first, when an animal is walking or in some other way actively interacting with its surroundings; second, during [[Rapid eye movement sleep|REM sleep]].<ref>{{cite journal | vauthors = Vanderwolf CH | title = Hippocampal electrical activity and voluntary movement in the rat | journal = Electroencephalography and Clinical Neurophysiology | volume = 26 | issue = 4 | pages = 407–418 | date = April 1969 | pmid = 4183562 | doi = 10.1016/0013-4694(69)90092-3 }}</ref> The function of theta has not yet been convincingly explained although numerous theories have been proposed.<ref name=Buzsaki2006>{{cite book | vauthors = Buzsáki G | title = Rhythms of the Brain | publisher = Oxford University Press | year = 2006 | isbn = 978-0-19-530106-9 | ref = refBuzsaki2006 }}</ref> The most popular hypothesis has been to relate it to learning and memory. An example would be the phase with which theta rhythms, at the time of stimulation of a neuron, shape the effect of that stimulation upon its synapses. What is meant here is that theta rhythms may affect those aspects of learning and memory that are dependent upon [[synaptic plasticity]].<ref>{{cite journal | vauthors = Huerta PT, Lisman JE | title = Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state | journal = Nature | volume = 364 | issue = 6439 | pages = 723–725 | date = August 1993 | pmid = 8355787 | doi = 10.1038/364723a0 | ref = refHuerta1993 | s2cid = 4358000 | bibcode = 1993Natur.364..723H }}</ref> It is well established that lesions of the [[medial septum]]{{snd}}the central node of the theta system{{snd}}cause severe disruptions of memory.<ref>{{cite journal | vauthors = Numan R, Feloney MP, Pham KH, Tieber LM | title = Effects of medial septal lesions on an operant go/no-go delayed response alternation task in rats | journal = Physiology & Behavior | volume = 58 | issue = 6 | pages = 1263–1271 | date = December 1995 | pmid = 8623030 | doi = 10.1016/0031-9384(95)02044-6 | url = https://www.sciencedirect.com/science/article/abs/pii/0031938495020446 | ref = refNuman1995 | access-date = 2020-03-09 | url-status = live | s2cid = 876694 | archive-url = https://web.archive.org/web/20210427200148/https://www.sciencedirect.com/science/article/abs/pii/0031938495020446 | archive-date = 2021-04-27 | url-access = subscription }}</ref> However, the medial septum is more than just the controller of theta; it is also the main source of [[cholinergic]] projections to the hippocampus.<ref name="Anderson"/> It has not been established that septal lesions exert their effects specifically by eliminating the theta rhythm.<ref>{{cite journal | vauthors = Kahana MJ, Seelig D, Madsen JR | title = Theta returns | journal = Current Opinion in Neurobiology | volume = 11 | issue = 6 | pages = 739–744 | date = December 2001 | pmid = 11741027 | doi = 10.1016/S0959-4388(01)00278-1 | ref = refKahana2001 | s2cid = 43829235 }}</ref>

=== Sharp waves ===
{{Main|Sharp waves and ripples}}

During sleep or during resting, when an animal is not engaged with its surroundings, the hippocampal EEG shows a pattern of irregular slow waves, somewhat larger in amplitude than theta waves. This pattern is occasionally interrupted by large surges called ''sharp waves''.<ref>{{cite journal | vauthors = Buzsáki G | title = Hippocampal sharp waves: their origin and significance | journal = Brain Research | volume = 398 | issue = 2 | pages = 242–252 | date = November 1986 | pmid = 3026567 | doi = 10.1016/0006-8993(86)91483-6 | ref = refBuzsaki1986 | s2cid = 37242634 }}</ref> These events are associated with bursts of spike activity lasting 50 to 100 milliseconds in pyramidal cells of CA3 and CA1. They are also associated with short-lived high-frequency EEG oscillations called "ripples", with frequencies in the range 150 to 200&nbsp;Hz in rats, and together they are known as [[sharp waves and ripples]]. Sharp waves are most frequent during sleep when they occur at an average rate of around 1 per second (in rats) but in a very irregular temporal pattern. Sharp waves are less frequent during inactive waking states and are usually smaller. Sharp waves have also been observed in humans and monkeys. In macaques, sharp waves are robust but do not occur as frequently as in rats.<ref name="Skaggs2007" />

Sharp waves appear to be associated with memory.<ref name="Wilson">{{cite journal | vauthors = Wilson MA, McNaughton BL | title = Reactivation of hippocampal ensemble memories during sleep | journal = Science | volume = 265 | issue = 5172 | pages = 676–679 | date = July 1994 | pmid = 8036517 | doi = 10.1126/science.8036517 | ref = refWilson1994 | s2cid = 890257 | bibcode = 1994Sci...265..676W }}</ref> Numerous later studies, have reported that when hippocampal place cells have overlapping spatial firing fields (and therefore often fire in near-simultaneity), they tend to show correlated activity during sleep following the behavioral session. This enhancement of correlation, commonly known as ''reactivation'', has been found to occur mainly during sharp waves.<ref>{{cite journal | vauthors = Jackson JC, Johnson A, Redish AD | title = Hippocampal sharp waves and reactivation during awake states depend on repeated sequential experience | journal = The Journal of Neuroscience | volume = 26 | issue = 48 | pages = 12415–12426 | date = November 2006 | pmid = 17135403 | pmc = 6674885 | doi = 10.1523/JNEUROSCI.4118-06.2006 | ref = refJackson2006 }}</ref> It has been proposed that sharp waves are, in fact, reactivations of neural activity patterns that were memorized during behavior, driven by strengthening of synaptic connections within the hippocampus.<ref>{{cite journal | vauthors = Sutherland GR, McNaughton B | title = Memory trace reactivation in hippocampal and neocortical neuronal ensembles | journal = Current Opinion in Neurobiology | volume = 10 | issue = 2 | pages = 180–186 | date = April 2000 | pmid = 10753801 | doi = 10.1016/S0959-4388(00)00079-9 | ref = refSutherland2000 | s2cid = 146539 | author-link1 = Grant Robert Sutherland }}</ref> This idea forms a key component of the "two-stage memory" theory,<ref name="Two-stage">{{cite journal | vauthors = Buzsáki G | title = Two-stage model of memory trace formation: a role for "noisy" brain states | journal = Neuroscience | volume = 31 | issue = 3 | pages = 551–570 | date = January 1989 | pmid = 2687720 | doi = 10.1016/0306-4522(89)90423-5 | s2cid = 23957660 }}</ref> advocated by Buzsáki and others, which proposes that memories are stored within the hippocampus during behavior and then later transferred to the [[neocortex]] during sleep. Sharp waves in [[Hebbian theory]] are seen as persistently repeated stimulations by presynaptic cells, of postsynaptic cells that are suggested to drive synaptic changes in the cortical targets of hippocampal output pathways.<ref name="Two-stage"/> Suppression of sharp waves and ripples in sleep or during immobility can interfere with memories expressed at the level of the behavior,<ref name="suppression of hippocampal ripples">{{cite journal | vauthors = Girardeau G, Benchenane K, Wiener SI, Buzsáki G, Zugaro MB | title = Selective suppression of hippocampal ripples impairs spatial memory | journal = Nature Neuroscience | volume = 12 | issue = 10 | pages = 1222–1223 | date = October 2009 | pmid = 19749750 | doi = 10.1038/nn.2384 | s2cid = 23637142 }}</ref><ref name="impair spatial learning study">{{cite journal | vauthors = Ego-Stengel V, Wilson MA | title = Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat | journal = Hippocampus | volume = 20 | issue = 1 | pages = 1–10 | date = January 2010 | pmid = 19816984 | pmc = 2801761 | doi = 10.1002/hipo.20707 }}</ref> nonetheless, the newly formed CA1 place cell code can re-emerge even after a sleep with abolished sharp waves and ripples, in spatially non-demanding tasks.<ref name="pmid27760158">{{cite journal | vauthors = Kovács KA, O'Neill J, Schoenenberger P, Penttonen M, Ranguel Guerrero DK, Csicsvari J | title = Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere with the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus | journal = PLOS ONE | volume = 11 | issue = 10 | article-number = e0164675 | date = 19 Nov 2016 | pmid = 27760158 | pmc = 5070819 | doi = 10.1371/journal.pone.0164675 | doi-access = free | bibcode = 2016PLoSO..1164675K }}</ref>

=== Long-term potentiation ===
{{See also|Long-term potentiation|Sleep and learning}}

Since at least the time of [[Santiago Ramon y Cajal|Ramon y Cajal]] (1852–1934), psychologists have speculated that the brain stores memory by altering the strength of connections between neurons that are simultaneously active.<ref>{{cite journal | vauthors = Ramón y Cajal S | title = The Croonian Lecture: La Fine Structure des Centres Nerveux | journal = Proceedings of the Royal Society | volume = 55 | pages = 444–468 | year = 1894 | doi = 10.1098/rspl.1894.0063 | issue = 331–335 | ref = refCajal1894 | bibcode = 1894RSPS...55..444C | doi-access = free }}</ref> This idea was formalized by [[Donald O. Hebb|Donald Hebb]] in 1949,<ref name="Hebb">{{cite book |last1=Hebb |first1=Donald O. |title=The organization of behavior: a neuropsychological theory |date=1974 |publisher=Wiley |location=New York |isbn=0-471-36727-3 |edition=11. [print.]}}</ref> but for many years remained unexplained. In 1973, [[Tim Bliss]] and [[Terje Lømo]] described a phenomenon in the rabbit hippocampus that appeared to meet Hebb's specifications: a change in synaptic responsiveness induced by brief strong activation and lasting for hours or days or longer.<ref>{{cite journal | vauthors = Bliss TV, Lomo T | title = Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path | journal = The Journal of Physiology | volume = 232 | issue = 2 | pages = 331–356 | date = July 1973 | pmid = 4727084 | pmc = 1350458 | doi = 10.1113/jphysiol.1973.sp010273 | ref = refBliss1973 }}</ref> This phenomenon was soon referred to as [[long-term potentiation]] (LTP). As a candidate mechanism for [[long-term memory]], LTP has since been studied intensively, and a great deal has been learned about it. However, the complexity and variety of the intracellular signaling cascades that can trigger LTP is acknowledged as preventing a more complete understanding.<ref name="ReferenceC">{{cite journal | vauthors = Malenka RC, Bear MF | title = LTP and LTD: an embarrassment of riches | journal = Neuron | volume = 44 | issue = 1 | pages = 5–21 | date = September 2004 | pmid = 15450156 | doi = 10.1016/j.neuron.2004.09.012 | ref = refMalenka2004 | s2cid = 79844 | doi-access = free }}</ref>

The hippocampus is a particularly favorable site for studying LTP because of its densely packed and sharply defined layers of neurons, but similar types of activity-dependent synaptic change have also been observed in many other brain areas.<ref>{{cite journal | vauthors = Cooke SF, Bliss TV | title = Plasticity in the human central nervous system | journal = Brain | volume = 129 | issue = Pt 7 | pages = 1659–1673 | date = July 2006 | pmid = 16672292 | doi = 10.1093/brain/awl082 | ref = refCooke2006 | doi-access = free }}</ref> The best-studied form of LTP has been seen in CA1 of the hippocampus and occurs at synapses that terminate on [[dendritic spine]]s and use the [[neurotransmitter]] [[glutamate]].<ref name="ReferenceC"/> The synaptic changes depend on a special type of [[glutamate receptor]], the [[NMDA receptor|''N''-methyl-D-aspartate (NMDA) receptor]], a [[cell surface receptor]] which has the special property of allowing calcium to enter the postsynaptic spine only when presynaptic activation and postsynaptic [[depolarization]] occur at the same time.<ref name=Nakazawa2004>{{cite journal | vauthors = Nakazawa K, McHugh TJ, Wilson MA, Tonegawa S | title = NMDA receptors, place cells and hippocampal spatial memory | journal = Nature Reviews. Neuroscience | volume = 5 | issue = 5 | pages = 361–372 | date = May 2004 | pmid = 15100719 | doi = 10.1038/nrn1385 | ref = refNakazawa2004 | s2cid = 7728258 }}</ref> Drugs that interfere with NMDA receptors block LTP and have major effects on some types of memory, especially spatial memory. [[Genetically modified mouse|Genetically modified mice]] that are [[Genetic engineering|modified]] to disable the LTP mechanism, also generally show severe memory deficits.<ref name=Nakazawa2004 />

==Research==
A [[brain implant]] for use as a [[hippocampal prosthesis]] has been the subject of research since the early 2000s.<ref name = "Berger_2005">{{cite book | vauthors = Berger TW, Brinton RD, Marmarelis VZ, Sheu BJ, Tanguay AR | chapter = Brain-implantable biomimetic electronics as a neural prosthesis for hippocampal memory function. | title = Toward replacement parts for the brain: implantable biomimetic electronics as neural prostheses. | chapter-url = https://books.google.com/books?id=8axpjcE0bqUC&pg=PA241 | publisher = MIT Press | location = Cambridge | date = 2005 | isbn = 978-0-262-02577-5 }}</ref>  It was reported in 2018 that a nonlinear multi-input multi-output model (MIMO) had been developed that in some studies, had been shown to restore and improve memory function.<ref name="Hampson">{{cite journal |vauthors=Hampson RE, Song D, Robinson BS, Fetterhoff D, Dakos AS, Roeder BM, She X, Wicks RT, Witcher MR, Couture DE, Laxton AW, Munger-Clary H, Popli G, Sollman MJ, Whitlow CT, Marmarelis VZ, Berger TW, Deadwyler SA |title=Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall |journal=J Neural Eng |volume=15 |issue=3 |page=036014 |date=June 2018 |pmid=29589592 |pmc=6576290 |doi=10.1088/1741-2552/aaaed7 |bibcode=2018JNEng..15c6014H |url=}}</ref> This has been followed by a modified version known as the memory decoding model (MDM).<ref name="Roeder2024">{{cite journal |vauthors=Roeder BM, She X, Dakos AS, Moore B, Wicks RT, Witcher MR, Couture DE, Laxton AW, Clary HM, Popli G, Liu C, Lee B, Heck C, Nune G, Gong H, Shaw S, Marmarelis VZ, Berger TW, Deadwyler SA, Song D, Hampson RE |title=Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall of stimulus features and categories |journal=Front Comput Neurosci |volume=18 |issue= |article-number=1263311 |date=2024 |pmid=38390007 |pmc=10881797 |doi=10.3389/fncom.2024.1263311 |doi-access=free |url=}}</ref> This model has been shown to have the potential use in significant modification of memory. A study concluded that further research could be pointed towards an evaluation of both models, in particular focusing on the hippocampal theta wave input.<ref name="Roeder2022">{{cite journal |vauthors=Roeder BM, Riley MR, She X, Dakos AS, Robinson BS, Moore BJ, Couture DE, Laxton AW, Popli G, Clary HM, Sam M, Heck C, Nune G, Lee B, Liu C, Shaw S, Gong H, Marmarelis VZ, Berger TW, Deadwyler SA, Song D, Hampson RE |title=Patterned Hippocampal Stimulation Facilitates Memory in Patients With a History of Head Impact and/or Brain Injury |journal=Front Hum Neurosci |volume=16 |issue= |article-number=933401 |date=2022 |pmid=35959242 |pmc=9358788 |doi=10.3389/fnhum.2022.933401 |doi-access=free |url=}}</ref>

==Clinical significance==

===Aging===
{{see also|Neurobiological effects of physical exercise#Structural growth|Aging brain|Memory and aging}} 
Normal aging is associated with a gradual decline in some types of memory, including [[episodic memory]] and [[working memory]] (or [[short-term memory]]). Because the hippocampus is thought to play a central role in memory, there has been considerable interest in the possibility that age-related declines could be caused by hippocampal deterioration.<ref name=Prull>{{cite book | vauthors = Prull MW, Gabrieli JD, Bunge SA | veditors = Craik FI, Salthouse TA | title = The handbook of aging and cognition | year = 2000 | chapter = Ch 2. Age-related changes in memory: A cognitive neuroscience perspective |pages = 105–107| publisher = Erlbaum | isbn = 978-0-8058-2966-2 | ref = refPrull2000 }}</ref> Some early studies reported substantial loss of neurons in the hippocampus of [[Old age|elderly people]], but later studies using more precise techniques found only minimal differences.<ref name=Prull /> Similarly, some [[MRI]] studies have reported shrinkage of the hippocampus in elderly people, but other studies have failed to reproduce this finding. There is, however, a reliable relationship between the size of the hippocampus and memory performance; so that where there is age-related shrinkage, memory performance will be impaired.<ref name=Prull /> There are also reports that memory tasks tend to produce less hippocampal activation in the elderly than in the young.<ref name=Prull /> Furthermore, a [[randomized control trial]] published in 2011 found that [[aerobic exercise]] could increase the size of the hippocampus in adults aged 55 to 80 and also improve spatial memory.<ref name=Erickson2011>{{cite journal | vauthors = Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF | title = Exercise training increases size of hippocampus and improves memory | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 7 | pages = 3017–3022 | date = February 2011 | pmid = 21282661 | pmc = 3041121 | doi = 10.1073/pnas.1015950108 | ref = refErickson2011 | doi-access = free | bibcode = 2011PNAS..108.3017E }}</ref>

===Dementia===
In [[Alzheimer's disease]] (and other forms of [[dementia]]), the hippocampus is one of the first regions of the brain to be damaged;<ref>{{cite journal | vauthors = Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, Bakardjian H, Benali H, Bertram L, Blennow K, Broich K, Cavedo E, Crutch S, Dartigues JF, Duyckaerts C, Epelbaum S, Frisoni GB, Gauthier S, Genthon R, Gouw AA, Habert MO, Holtzman DM, Kivipelto M, Lista S, Molinuevo JL, O'Bryant SE, Rabinovici GD, Rowe C, Salloway S, Schneider LS, Sperling R, Teichmann M, Carrillo MC, Cummings J, Jack CR | title = Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria | journal = Alzheimer's & Dementia | volume = 12 | issue = 3 | pages = 292–323 | date = March 2016 | pmid = 27012484 | pmc = 6417794 | doi = 10.1016/j.jalz.2016.02.002 }}</ref>
[[short-term memory|short-term memory loss]] and [[disorientation]] are included among the early symptoms. [[Amyloid beta]] deposits begin in the [[frontal lobes]] before the signs of [[neurofibrillary tangle]]s are seen in the hippocampus.<ref name="Hayat">{{cite journal |vauthors=Hayat M, Syed RA, Qaiser H, Uzair M, Al-Regaiey K, Khallaf R, Albassam LA, Kaleem I, Wang X, Wang R, Bhatti MS, Bashir S |title=Decoding molecular mechanisms: brain aging and Alzheimer's disease |journal=Neural Regen Res |volume=20 |issue=8 |pages=2279–2299 |date=August 2025 |pmid=39104174 |pmc=11759015 |doi=10.4103/NRR.NRR-D-23-01403 |doi-access=free |url=}}</ref> Damage to the hippocampus can also result from oxygen starvation ([[hypoxia (medical)|hypoxia]]), [[encephalitis]], or [[medial temporal lobe epilepsy]]. Extensive, bilateral hippocampal damage may cause [[anterograde amnesia]]: the inability to form and retain new [[memory|memories]]. 

Dementia is very often caused by [[cerebral ischemia]] that is believed to trigger changes in the hippocampus. Changes in [[Hippocampal subfields|CA1]], the hippocampal area that underlies [[episodic memory]], cause episodic memory impairment, the earliest symptom of post-ischemic dementia.<ref name="Pluta">{{cite web |title=Cerebral Ischemia |url=https://www.ncbi.nlm.nih.gov/books/NBK575741/ |publisher=Exon Publications |access-date=6 January 2025 |date=2021}}</ref>

===Stress===
The hippocampus contains high levels of [[glucocorticoid receptor]]s, which make it more vulnerable to [[chronic stress|long-term stress]] than most other [[List of regions in the human brain|brain areas]].<ref>{{cite journal | vauthors = Joëls M | title = Functional actions of corticosteroids in the hippocampus | journal = European Journal of Pharmacology | volume = 583 | issue = 2–3 | pages = 312–321 | date = April 2008 | pmid = 18275953 | doi = 10.1016/j.ejphar.2007.11.064 | ref = refJoels2008 }}</ref> There is evidence that humans having experienced severe, long-lasting traumatic stress show atrophy of the hippocampus more than of other parts of the brain.<ref>{{cite journal | vauthors = Woon FL, Sood S, Hedges DW | title = Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: a meta-analysis | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 34 | issue = 7 | pages = 1181–1188 | date = October 2010 | pmid = 20600466 | doi = 10.1016/j.pnpbp.2010.06.016 | s2cid = 34575365 }}</ref> These effects show up in [[post-traumatic stress disorder]],<ref>{{cite journal | vauthors = Karl A, Schaefer M, Malta LS, Dörfel D, Rohleder N, Werner A | title = A meta-analysis of structural brain abnormalities in PTSD | journal = Neuroscience and Biobehavioral Reviews | volume = 30 | issue = 7 | pages = 1004–1031 | year = 2006 | pmid = 16730374 | doi = 10.1016/j.neubiorev.2006.03.004 | s2cid = 15511760 }}</ref> and they may contribute to the hippocampal atrophy reported in [[schizophrenia]]<ref>{{cite journal | vauthors = Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET | title = Meta-analysis of regional brain volumes in schizophrenia | journal = The American Journal of Psychiatry | volume = 157 | issue = 1 | pages = 16–25 | date = January 2000 | pmid = 10618008 | doi = 10.1176/ajp.157.1.16 | author2-link = Sophia Rabe-Hesketh | s2cid = 22522434 }}</ref> and [[major depressive disorder|severe depression]].<ref>{{cite journal | vauthors = Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC | title = Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder | journal = Archives of General Psychiatry | volume = 68 | issue = 7 | pages = 675–690 | date = July 2011 | pmid = 21727252 | doi = 10.1001/archgenpsychiatry.2011.60 | doi-access = free }} see also MRI database at [http://sites.google.com/site/depressiondatabase/ www.depressiondatabase.org] {{Webarchive|url=https://web.archive.org/web/20110929165423/http://sites.google.com/site/depressiondatabase/ |date=2011-09-29 }}</ref> Anterior hippocampal volume in children is positively correlated with parental family income and this correlation is thought to be mediated by income-related stress.<ref>{{cite journal | vauthors = Decker AL, Duncan K, Finn AS, Mabbott DJ | title = Children's family income is associated with cognitive function and volume of anterior not posterior hippocampus | journal = Nature Communications | volume = 11 | issue = 1 | article-number = 4040 | date = August 2020 | pmid = 32788583 | pmc = 7423938 | doi = 10.1038/s41467-020-17854-6 | bibcode = 2020NatCo..11.4040D }}</ref> A study has revealed atrophy as a result of depression, but this can be stopped with anti-depressants even if they are not effective in relieving other symptoms.<ref>{{cite journal | vauthors = Campbell S, Macqueen G | title = The role of the hippocampus in the pathophysiology of major depression | journal = Journal of Psychiatry & Neuroscience | volume = 29 | issue = 6 | pages = 417–426 | date = November 2004 | doi = 10.1139/jpn.0441 | pmid = 15644983 | pmc = 524959 | ref = refCampbell2004 }}</ref>

Chronic stress resulting in elevated levels of [[glucocorticoid]]s, notably of [[cortisol]], is seen to be a cause of neuronal atrophy in the hippocampus. This atrophy results in a smaller hippocampal volume which is also seen in [[Cushing's syndrome]]. The higher levels of cortisol in Cushing's syndrome is usually the result of medications taken for other conditions.<ref name="Starkman">{{cite journal | vauthors = Starkman MN, Giordani B, Gebarski SS, Berent S, Schork MA, Schteingart DE | title = Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease | journal = Biological Psychiatry | volume = 46 | issue = 12 | pages = 1595–1602 | date = December 1999 | pmid = 10624540 | doi = 10.1016/s0006-3223(99)00203-6 | s2cid = 7294913 }}</ref><ref name="IoM">{{cite book | author = Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders |title=Overview of the Glutamatergic System |url= https://www.ncbi.nlm.nih.gov/books/NBK62187/ |publisher=National Academies Press (US)|year=2011|access-date=5 February 2017|archive-date=1 September 2018|archive-url=https://web.archive.org/web/20180901114814/https://www.ncbi.nlm.nih.gov/books/NBK62187/|url-status=live}}</ref> Neuronal loss also occurs as a result of impaired neurogenesis. Another factor that contributes to a smaller hippocampal volume is that of dendritic retraction where dendrites are shortened in length and reduced in number, in response to increased glucocorticoids. This dendritic retraction is reversible.<ref name=IoM/> After treatment with medication to reduce cortisol in Cushing's syndrome, the hippocampal volume is seen to be restored by as much as 10%.<ref name=Starkman/> This change is seen to be due to the reforming of the dendrites.<ref name=IoM/> This dendritic restoration can also happen when stress is removed. There is, however, evidence derived mainly from studies using rats that stress occurring shortly after birth can affect hippocampal function in ways that persist throughout life.<ref>{{cite book | vauthors = Garcia-Segura LM | title = Hormones and Brain Plasticity |pages=170–171| year = 2009 | publisher = Oxford University Press US | isbn = 978-0-19-532661-1 | ref = refGarciaSegura2009 }}</ref>

Sex-specific responses to stress have also been demonstrated in the rat to have an effect on the hippocampus. Chronic stress in the male rat showed dendritic retraction and cell loss in the CA3 region but this was not shown in the female. This was thought to be due to neuroprotective ovarian hormones.<ref>{{cite journal | vauthors = Conrad CD | title = Chronic stress-induced hippocampal vulnerability: the glucocorticoid vulnerability hypothesis | journal = Reviews in the Neurosciences | volume = 19 | issue = 6 | pages = 395–411 | year = 2008 | pmid = 19317179 | pmc = 2746750 | doi = 10.1515/revneuro.2008.19.6.395 }}</ref><ref>{{cite journal | vauthors = Ortiz JB, McLaughlin KJ, Hamilton GF, Baran SE, Campbell AN, Conrad CD | title = Cholesterol and perhaps estradiol protect against corticosterone-induced hippocampal CA3 dendritic retraction in gonadectomized female and male rats | journal = Neuroscience | volume = 246 | pages = 409–421 | date = August 2013 | pmid = 23618757 | pmc = 3703463 | doi = 10.1016/j.neuroscience.2013.04.027 }}</ref> In rats, DNA damage increases in the hippocampus under conditions of stress.<ref name="pmid20226828">{{cite journal | vauthors = Consiglio AR, Ramos AL, Henriques JA, Picada JN | title = DNA brain damage after stress in rats | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 34 | issue = 4 | pages = 652–656 | date = May 2010 | pmid = 20226828 | doi = 10.1016/j.pnpbp.2010.03.004 | s2cid = 38959073 | doi-access = free }}</ref>

====PTSD====

Some studies shows correlation of reduced hippocampus volume and [[post-traumatic stress disorder]] (PTSD).<ref>{{cite journal | vauthors = Bonne O, Vythilingam M, Inagaki M, Wood S, Neumeister A, Nugent AC, Snow J, Luckenbaugh DA, Bain EE, Drevets WC, Charney DS | title = Reduced posterior hippocampal volume in posttraumatic stress disorder | journal = The Journal of Clinical Psychiatry | volume = 69 | issue = 7 | pages = 1087–1091 | date = July 2008 | pmid = 18572983 | pmc = 2684983 | doi = 10.4088/jcp.v69n0707 }}</ref><ref>{{cite journal | vauthors = Apfel BA, Ross J, Hlavin J, Meyerhoff DJ, Metzler TJ, Marmar CR, Weiner MW, Schuff N, Neylan TC | title = Hippocampal volume differences in Gulf War veterans with current versus lifetime posttraumatic stress disorder symptoms | journal = Biological Psychiatry | volume = 69 | issue = 6 | pages = 541–548 | date = March 2011 | pmid = 21094937 | pmc = 3259803 | doi = 10.1016/j.biopsych.2010.09.044 | url = http://www.biologicalpsychiatryjournal.com/article/S0006-3223(10)01013-9/fulltext | access-date = 2017-08-14 | url-status = live | archive-url = https://web.archive.org/web/20191204064536/https://www.sciencedaily.com/releases/2011/03/110322105257.htm | archive-date = 2019-12-04 }}</ref> A study of [[Vietnam War]] combat veterans with PTSD showed a 20% reduction in the volume of their hippocampus compared with veterans with no such symptoms.<ref>{{cite book| vauthors = Carlson NR |year=2014|title=Physiology of Behavior|edition=11|publisher=Pearson Education|page=624|isbn=978-1-292-02320-5}}</ref> This finding was not replicated in those with chronic PTSD, traumatized at an [[Ramstein air show disaster|air show plane crash in 1988]] (Ramstein, Germany).<ref name="Jatzko">{{cite journal | vauthors = Jatzko A, Rothenhöfer S, Schmitt A, Gaser C, Demirakca T, Weber-Fahr W, Wessa M, Magnotta V, Braus DF | title = Hippocampal volume in chronic posttraumatic stress disorder (PTSD): MRI study using two different evaluation methods | journal = Journal of Affective Disorders | volume = 94 | issue = 1–3 | pages = 121–126 | date = August 2006 | pmid = 16701903 | doi = 10.1016/j.jad.2006.03.010 | url = http://dbm.neuro.uni-jena.de/pdf-files/Jatzko-JAD06.pdf | access-date = 2017-08-14 | url-status = live | archive-url = https://web.archive.org/web/20131019153804/http://dbm.neuro.uni-jena.de/pdf-files/Jatzko-JAD06.pdf | archive-date = 2013-10-19 }}</ref> It is also the case that non-combat twin brothers of [[Vietnam veteran]]s with PTSD also had smaller hippocampi than other controls, raising questions about the nature of the correlation.<ref>{{cite magazine | vauthors = Stern R |date=September–October 2019 |title=The New Phrenology |url=https://skepticalinquirer.org/2019/09/the-new-phrenology/ |magazine=[[Skeptical Inquirer]] |publisher=[[Center for Inquiry]] |volume=43 |issue=5 |pages=52–56 |access-date=2020-03-20 |archive-date=2020-04-29 |archive-url=https://web.archive.org/web/20200429221719/https://skepticalinquirer.org/2019/09/the-new-phrenology/ |url-status=live }}</ref> A 2016 study strengthened the theory that a smaller hippocampus increases the risk for post-traumatic stress disorder, and a larger hippocampus increases the likelihood of efficacious treatment.<ref>{{cite journal | vauthors = Rubin M, Shvil E, Papini S, Chhetry BT, Helpman L, Markowitz JC, Mann JJ, Neria Y | title = Greater hippocampal volume is associated with PTSD treatment response | journal = Psychiatry Research: Neuroimaging | volume = 252 | pages = 36–39 | date = June 2016 | pmid = 27179314 | pmc = 4896219 | doi = 10.1016/j.pscychresns.2016.05.001 }}</ref>

====Transient global amnesia====

[[Transient global amnesia]] is a syndrome of unknown cause that results in a sudden and temporary anterograde amnesia and variable past memory loss. An attack usually lasts for up to 24 hours during which time the memory loss is experienced. The only diagnostic evidence of TGA is given by DWI-MRI that shows lesions as small dots in the CA1 subfield.<ref name="Sparaco2022">{{cite journal |vauthors=Sparaco M, Pascarella R, Muccio CF, Zedde M |title=Forgetting the Unforgettable: Transient Global Amnesia Part II: A Clinical Road Map |journal=J Clin Med |volume=11 |issue=14 |date=July 2022 |page=3940 |pmid=35887703 |pmc=9319625 |doi=10.3390/jcm11143940 |doi-access=free |url=}} </ref><ref name="Sparaco2">{{cite journal |vauthors=Sparaco M, Pascarella R, Muccio CF, Zedde M |title=Forgetting the Unforgettable: Transient Global Amnesia Part I: Pathophysiology and Etiology |journal=J Clin Med |volume=11 |issue=12 |date=June 2022 |page=3373 |pmid=35743444 |pmc=9225344 |doi=10.3390/jcm11123373 |doi-access=free |url=}}</ref>
The lesions are detectable from around 24 to 96 hours after symptoms onset, and can be seen to have been resolved at  a six-month follow-up.<ref name="Bartsch">{{cite journal |vauthors=Bartsch T, Alfke K, Stingele R, Rohr A, Freitag-Wolf S, Jansen O, Deuschl G |title=Selective affection of hippocampal CA-1 neurons in patients with transient global amnesia without long-term sequelae |journal=Brain |volume=129 |issue=Pt 11 |pages=2874–84 |date=November 2006 |pmid=17003071 |doi=10.1093/brain/awl248 |url=}}</ref> The lesions are between 1 and 5 mm, and can be single or multiple and may be confined to either  hemisphere.<ref name="Sparaco2022"/><ref name="Sparaco2"/> Lesions in the dominant hemisphere affect episodic verbal memory and those in the non-dominant hemisphere affect visuospatial memory.<ref name="Bartsch"/>

CA1 lesions shows selective affect over other CA subfields.<ref name="Bartsch2">{{cite journal |vauthors=Bartsch T, Döhring J, Reuter S, Finke C, Rohr A, Brauer H, Deuschl G, Jansen O |title=Selective neuronal vulnerability of human hippocampal CA1 neurons: lesion evolution, temporal course, and pattern of hippocampal damage in diffusion-weighted MR imaging |journal=J Cereb Blood Flow Metab |volume=35 |issue=11 |pages=1836–45 |date=November 2015 |pmid=26082014 |pmc=4635239 |doi=10.1038/jcbfm.2015.137 |url=}}</ref> The selective vulnerability of CA1 neurons suggests a cause of metabolic stress that could result from emotional or behavioral stress.<ref name="Bartsch2" /><ref name="Szabo">{{cite book | vauthors = Szabo K | title = The Hippocampus in Clinical Neuroscience | chapter = Transient global amnesia | series = Frontiers of Neurology and Neuroscience | year = 2014 | volume = 34 | issue = 5633 | pages = 143–149 | doi = 10.1159/000356431 | pmid = 24777137 | isbn = 978-3-318-02567-5 | chapter-url = http://www.bmj.com/cgi/content/short/4/5633/723-a | access-date = 2018-08-15 | archive-date = 2021-09-23 | archive-url = https://web.archive.org/web/20210923091233/https://www.bmj.com/content/4/5633/723.2 | url-status = live }}</ref> Other possible causes have been debated including cerebral venous reflex, arterial ischema, epilepsy, and migraine.<ref name="Sparaco2"/> TGA as a ''network disease'' has also been put forward; DTI studies show a decreased connectivity between brain regions that may impact the hippocampus.<ref name="Sparaco2"/>

===Epilepsy===
[[File:Epilepsy- right hippocampal seizure onset.png|thumb|180px| An EEG showing epilepsy right-hippocampal seizure onset]]
[[File:Epilepsy-left hippocampal seizure onset.png|thumb|right|180px| An EEG showing epilepsy left-hippocampal seizure onset]]
The hippocampus is one of the few brain regions where new neurons are generated. This process of [[neurogenesis]] is confined to the dentate gyrus.<ref name="ReferenceD">{{cite journal | vauthors = Kuruba R, Hattiangady B, Shetty AK | title = Hippocampal neurogenesis and neural stem cells in temporal lobe epilepsy | journal = Epilepsy & Behavior | volume = 14 | issue = Suppl 1 | pages = 65–73 | date = January 2009 | pmid = 18796338 | pmc = 2654382 | doi = 10.1016/j.yebeh.2008.08.020 | ref = refKuruba2009 }}</ref> Neurogenesis can be positively affected by exercise or negatively affected by [[epileptic seizure]]s.<ref name="ReferenceD"/>

Seizures in [[temporal lobe epilepsy]] can affect the normal development of new neurons and can cause tissue damage. [[Hippocampal sclerosis]]  specific to the mesial temporal lobe, is the most common type of such tissue damage.<ref name="Thom">{{cite journal | vauthors = Thom M | title = Review: Hippocampal sclerosis in epilepsy: a neuropathology review | journal = Neuropathology and Applied Neurobiology | volume = 40 | issue = 5 | pages = 520–543 | date = August 2014 | pmid = 24762203 | pmc = 4265206 | doi = 10.1111/nan.12150 }}</ref><ref>{{cite journal | vauthors = Chang BS, Lowenstein DH | title = Epilepsy | journal = The New England Journal of Medicine | volume = 349 | issue = 13 | pages = 1257–1266 | date = September 2003 | pmid = 14507951 | doi = 10.1056/NEJMra022308 | ref = refChang2003 | author-link2 = Daniel H. Lowenstein (physician) }}</ref> It is not yet clear, however, whether the epilepsy is usually caused by hippocampal abnormalities or whether the hippocampus is damaged by cumulative effects of seizures.<ref>{{cite journal | vauthors = Sloviter RS | title = The neurobiology of temporal lobe epilepsy: too much information, not enough knowledge | journal = Comptes Rendus Biologies | volume = 328 | issue = 2 | pages = 143–153 | date = February 2005 | pmid = 15771000 | doi = 10.1016/j.crvi.2004.10.010 | url = https://comptes-rendus.academie-sciences.fr/biologies/articles/10.1016/j.crvi.2004.10.010/ | ref = refSloviter2005 | url-access = subscription }}</ref> However, in experimental settings where repetitive seizures are artificially induced in animals, hippocampal damage is a frequent result. This may be a consequence of the concentration of excitable [[glutamate receptor]]s in the hippocampus. Hyperexcitability can lead to [[cytotoxicity]] and cell death.<ref name="IoM"/> It may also have something to do with the hippocampus being a site of continuous neurogenesis, and to abnormalities in this process.<ref name="ReferenceD"/><ref name=IoM/>

===Schizophrenia===
A reduction in hippocampal volume is well reported in those with schizophrenia.<ref name="Antoniades">{{cite journal | vauthors = Antoniades M, Schoeler T, Radua J, Valli I, Allen P, Kempton MJ, McGuire P | title = Verbal learning and hippocampal dysfunction in schizophrenia: A meta-analysis | journal = Neuroscience and Biobehavioral Reviews | volume = 86 | pages = 166–175 | date = March 2018 | pmid = 29223768 | pmc = 5818020 | doi = 10.1016/j.neubiorev.2017.12.001 | url = http://discovery.ucl.ac.uk/10045938/1/Antoniades_Verbal%20learning%20and%20hippocampal.pdf | access-date = 2018-11-23 | url-status = live | archive-url = https://web.archive.org/web/20180725201206/http://discovery.ucl.ac.uk/10045938/1/Antoniades_Verbal%20learning%20and%20hippocampal.pdf | archive-date = 2018-07-25 }}</ref><ref name="Morris and Amaral2024A">{{cite book |last1=Morris |first1=Richard |last2=Amaral |first2=David |title=The Hippocampus Book |date=2024 |publisher=Oxford University Press |location=New York |isbn=978-0-19-006532-4 |pages=923–925 |edition=Second}}</ref> The left hippocampus seems to be affected more than the right.<ref name="ReferenceA">{{cite journal | vauthors = Harrison PJ | title = The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications | journal = Psychopharmacology | volume = 174 | issue = 1 | pages = 151–162 | date = June 2004 | pmid = 15205886 | doi = 10.1007/s00213-003-1761-y | ref = refHarrison2004 | s2cid = 12388920 }}</ref> The volume reduction is modest but consistent, and can be first seen in the [[Prodrome|prodromal stage]] with modest progression shown as the disease advances.<ref name="Morris and Amaral2024A"/> The reduced volume has been shown to be independent of treatment with antipsychotics. Some studies suggest that hippocampal alterations play a role in causing the psychotic symptoms of schizophrenia.<ref>{{cite journal | vauthors = Duncan LE, Li T, Salem M, Li W, Mortazavi L, Senturk H, Shahverdizadeh N, Vesuna S, Shen H, Yoon J, Wang G, Ballon J, Tan L, Pruett BS, Knutson B, Deisseroth K, Giardino WJ | title = Mapping the cellular etiology of schizophrenia and complex brain phenotypes | journal = Nature Neuroscience | volume = 28 | issue = 2 | pages = 248–258 | date = February 2025 | pmid = 39833308 | doi = 10.1038/s41593-024-01834-w | ref = refDuncan2025 | pmc = 11802450 }}</ref><ref name="Pines2025">{{cite journal | vauthors = Pines AR, Frandsen SB, Drew W, Meyer GM, Howard C, Palm ST, Schaper FJ, Lin C, Butenko K, Ferguson MA, Friedrich MU, Grafman JH, Kappel AD, Neudorfer C, Rost NS, Sanderson LL, Taylor JJ, Wu O, Kletenik I, Vogel JW, Cohen AL, Horn A, Fox MD, Silbersweig D, Siddiqi SH | title = Mapping Lesions That Cause Psychosis to a Human Brain Circuit and Proposed Stimulation Target | journal = JAMA Psychiatry | date = February 2025 | volume = 82 | issue = 4 | pages = 368–378 | pmid = 39937525 | doi = 10.1001/jamapsychiatry.2024.4534 | pmc = 11822627 | pmc-embargo-date = February 12, 2026  }}</ref> It has been suggested that hippocampal dysfunction might produce an alteration of dopamine release in the [[basal ganglia]], thereby indirectly affecting the integration of information in the [[prefrontal cortex]].<ref>{{cite journal | vauthors = Goto Y, Grace AA | title = Limbic and cortical information processing in the nucleus accumbens | journal = Trends in Neurosciences | volume = 31 | issue = 11 | pages = 552–558 | date = November 2008 | pmid = 18786735 | pmc = 2884964 | doi = 10.1016/j.tins.2008.08.002 | ref = refGoto2008 }}</ref> 

In those with [[psychosis]] the greatest reduction is seen to be in CA3 and CA2 subfields, and a correlation has been made between the reduced volume and memory dysfunction.<ref name="Morris and Amaral2024A"/> A reduced hippocampal volume has been shown to result in a decreased connectivity between the hippocampus and the [[prefrontal cortex]], with the declarative memory characteristic of hippocampal function becoming selectively impaired.<ref name="Antoniades"/> The impaired connectivity is evident both at [[Resting state fMRI|rest and during task-activity]].<ref name="Morris and Amaral2024A"/> 

Evidence of dysfunctional [[GABA]] transmission  has been shown in studies of the whole hippocampus.<ref name="Morris and Amaral2024A"/><ref>{{Cite journal |last1=Heckers |first1=Stephan |last2=Konradi |first2=Christine |date=2015-09-01 |title=GABAergic mechanisms of hippocampal hyperactivity in schizophrenia |journal=Schizophrenia Research |series=The GABA System in Schizophrenia: Cells, Molecules and Microcircuitry |volume=167 |issue=1 |pages=4–11 |doi=10.1016/j.schres.2014.09.041 |issn=0920-9964 |pmc=4402105 |pmid=25449711}}</ref>Another noted change in the hippocampus in schizophrenia is a reduced [[Muscarinic acetylcholine receptor M4|
M4 muscarinic cholinergic receptor]], but an unaffected [[Muscarinic acetylcholine receptor M1|
M1 receptor]].<ref name="Morris and Amaral2024A"/> Reduced [[neurogenesis]] has been shown in the dentate gyrus with a noted reduction in the density of neurons and [[oligodendrocyte]]s in the dentate gyrus and hilus.<ref name="Morris and Amaral2024A"/>

Hyperactivity in the hippocampus has been suggested to be implicated in schizophrenic [[psychosis]].<ref name="Morris and Amaral2024A"/> The CA1 subfield is mostly indicated to be affected, and hyperactivity almost exclusively found in the anterior hippocampus.<ref name="Morris and Amaral2024A"/> It has been suggested that hippocampal dysfunction might produce an alteration of dopamine release in the [[basal ganglia]], thereby indirectly affecting the integration of information in the [[prefrontal cortex]].<ref>{{cite journal | vauthors = Goto Y, Grace AA | title = Limbic and cortical information processing in the nucleus accumbens | journal = Trends in Neurosciences | volume = 31 | issue = 11 | pages = 552–558 | date = November 2008 | pmid = 18786735 | pmc = 2884964 | doi = 10.1016/j.tins.2008.08.002 | ref = refGoto2008 }}</ref> Many post-mortem studies have assessed the hippocampal subfield proteins. Evidence of hyperactivity was a consistent finding.<ref name="Morris and Amaral2024A"/> In CA1 [[BDNF]] (an indication of hyperactivity) was notably increased, but the synaptic protein changes seen in the other subfields were not affected.<ref name="Morris and Amaral2024A"/> The strongest change was seen in CA3 synaptic anatomy with an increase in the dendritic spines on the apical dendrites of CA3 pyramidal neurons. This was most evident at the site of the entrance of the mossy fiber pathway to CA3 neurons. All three subfields have distinct molecular changes associated with schizophrenia.<ref name="Morris and Amaral2024A"/>

=== Microcephaly ===

Hippocampus atrophy has been characterized in those with [[microcephaly]].<ref>{{cite journal | vauthors = Bilgüvar K, Oztürk AK, Louvi A, Kwan KY, Choi M, Tatli B, Yalnizoğlu D, Tüysüz B, Cağlayan AO, Gökben S, Kaymakçalan H, Barak T, Bakircioğlu M, Yasuno K, Ho W, Sanders S, Zhu Y, Yilmaz S, Dinçer A, Johnson MH, Bronen RA, Koçer N, Per H, Mane S, Pamir MN, Yalçinkaya C, Kumandaş S, Topçu M, Ozmen M, Sestan N, Lifton RP, State MW, Günel M | title = Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations | journal = Nature | volume = 467 | issue = 7312 | pages = 207–210 | date = September 2010 | pmid = 20729831 | pmc = 3129007 | doi = 10.1038/nature09327 | bibcode = 2010Natur.467..207B }}</ref> Mouse models with [[WDR62|Wdr62]] mutations which recapitulate human [[point mutation]]s show a deficiency in hippocampal development, and [[neurogenesis]].<ref name="Shohayeb_2020">{{cite journal | vauthors = Shohayeb B, Ho UY, Hassan H, Piper M, Ng DC | title = The Spindle-Associated Microcephaly Protein, WDR62, Is Required for Neurogenesis and Development of the Hippocampus | journal = Frontiers in Cell and Developmental Biology | volume = 8 | issue = | article-number = 549353 | date = 2020 | pmid = 33042990 | pmc = 7517699 | doi = 10.3389/fcell.2020.549353 | doi-access = free }}</ref>

==Other animals==
===Other vertebrates===
Non-mammalian [[vertebrate]]s lack a brain structure that looks like the mammalian hippocampus, but they have one that is considered [[Homology (biology)|homologous]] to it. The hippocampus is in essence part of the allocortex. Only mammals have a fully developed cortex, but the structure it evolved from, called the [[pallium (neuroanatomy)|pallium]], is present in all vertebrates, even the most primitive ones such as the [[lamprey]] or [[hagfish]].<ref>{{cite journal | vauthors = Aboitiz F, Morales D, Montiel J | title = The evolutionary origin of the mammalian isocortex: towards an integrated developmental and functional approach | journal = The Behavioral and Brain Sciences | volume = 26 | issue = 5 | pages = 535–552 | date = October 2003 | pmid = 15179935 | doi = 10.1017/S0140525X03000128 | ref = refAboitiz2003 | s2cid = 6599761 }}</ref><ref>{{cite book | vauthors = Bingman VP, Salas C, Rodriguez F | date = 2009 | chapter = Evolution of the Hippocampus | veditors = Binder MD, Hirokawa N, Windhorst U | title = Encyclopedia of Neuroscience | pages = 1356–1360 | publisher = Springer | location = Berlin, Heidelberg | doi = 10.1007/978-3-540-29678-2_3158 | isbn = 978-3-540-29678-2 }}</ref> The pallium is usually divided into three zones: medial, lateral and dorsal. The medial pallium forms the precursor of the hippocampus. It does not resemble the hippocampus visually because the layers are not warped into an S shape or enfolded by the dentate gyrus, but the homology is indicated by strong chemical and functional affinities. There is evidence that these hippocampal-like structures are involved in spatial cognition in [[reptile]]s, and in [[fish]].<ref>{{cite journal | vauthors = Rodríguez F, López JC, Vargas JP, Broglio C, Gómez Y, Salas C | title = Spatial memory and hippocampal pallium through vertebrate evolution: insights from reptiles and teleost fish | journal = Brain Research Bulletin | volume = 57 | issue = 3–4 | pages = 499–503 | year = 2002 | pmid = 11923018 | doi = 10.1016/S0361-9230(01)00682-7 | ref = refRodriguez2002 | s2cid = 40858078 }}</ref>

====Fish====
In [[teleost]] fish, the forebrain is everted (like an inside-out sock) with structures that lie on the outside, as contrasted with other vertebrate structures that lie in the interior, next to the ventricles.<ref name="Hegarty2024">{{cite journal |vauthors=Hegarty BE, Gruenhagen GW, Johnson ZV, Baker CM, Streelman JT |title=Spatially resolved cell atlas of the teleost telencephalon and deep homology of the vertebrate forebrain |journal=Commun Biol |volume=7 |issue=1 |article-number=612 |date=May 2024 |pmid=38773256 |pmc=11109250 |doi=10.1038/s42003-024-06315-1 |url=}}</ref> One of the consequences of this is that the medial pallium, the hippocampal zone of a typical vertebrate, is thought to correspond to the lateral pallium of a typical fish.<ref>{{cite journal |vauthors=Broglio C, Gómez A, Durán E, Ocaña FM, Jiménez-Moya F, Rodríguez F, Salas C |title=Hallmarks of a common forebrain vertebrate plan: specialized pallial areas for spatial, temporal and emotional memory in actinopterygian fish |journal=Brain Res Bull |volume=66 |issue=4–6 |pages=277–81 |date=September 2005 |pmid=16144602 |doi=10.1016/j.brainresbull.2005.03.021 |url=}}</ref> Several types of fish (particularly goldfish) have been shown experimentally to have strong spatial memory abilities, even forming [[cognitive map]]s of the areas they inhabit.<ref name="Jacobs2003" /> Studies in [[goldfish]] show that damage to both the lateral pallium, and the medial pallium impairs spatial memory coding.<ref name="Givon">{{cite journal |vauthors=Givon S, Altsuler-Nagar R, Oring N, Vinepinsky E, Segev R |title=Lateral and medial telencephalic pallium lesions impair spatial memory in goldfish |journal=Brain Res Bull |volume= 204|issue= |article-number=110802 |date=October 2023 |pmid=39492553 |doi=10.1016/j.brainresbull.2023.110802 |url=|doi-access=free }}</ref><ref>{{cite journal | vauthors = Vargas JP, Bingman VP, Portavella M, López JC | title = Telencephalon and geometric space in goldfish | journal = The European Journal of Neuroscience | volume = 24 | issue = 10 | pages = 2870–2878 | date = November 2006 | pmid = 17156211 | doi = 10.1111/j.1460-9568.2006.05174.x | ref = refVargas2006 | s2cid = 23884328 }}</ref> It is not clear if the medial pallium plays a similar role in basal vertebrates, such as [[shark]]s and [[Batomorphi|rays]], or even [[lamprey]]s and [[hagfish]].<ref>{{cite journal | vauthors = Docampo-Seara A, Lagadec R, Mazan S, Rodríguez MA, Quintana-Urzainqui I, Candal E | title = Study of pallial neurogenesis in shark embryos and the evolutionary origin of the subventricular zone | journal = Brain Structure & Function | volume = 223 | issue = 8 | pages = 3593–3612 | date = November 2018 | pmid = 29980930 | doi = 10.1007/s00429-018-1705-2 | ref = Docampo-Seara2018 | hdl-access = free | doi-access = free | hdl = 10347/17636 }}</ref> The dorsolateral pallium of the teleost is considered as homologous to the hippocampus in terrestrial vertebrates.<ref name="Animals2021">{{cite journal |vauthors=Rodríguez F, Quintero B, Amores L, Madrid D, Salas-Peña C, Salas C |title=Spatial Cognition in Teleost Fish: Strategies and Mechanisms |journal=Animals |volume=11 |issue=8 |date=July 2021 |page=2271 |pmid=34438729 |pmc=8388456 |doi=10.3390/ani11082271 |doi-access=free |url=}}</ref> In 2023, the goldfish brain was mapped by molecular parcellization showing that its telencephalon subregions were homogeneous to the hippocampal subfields in the mouse.<ref name="Givon"/>

====Birds====
{{See also|Avian pallium}}
In birds, the correspondence is sufficiently well established that most anatomists refer to the medial pallial zone as the "avian hippocampus".<ref>{{cite journal | vauthors = Colombo M, Broadbent N | title = Is the avian hippocampus a functional homologue of the mammalian hippocampus? | journal = Neuroscience and Biobehavioral Reviews | volume = 24 | issue = 4 | pages = 465–484 | date = June 2000 | pmid = 10817844 | doi = 10.1016/S0149-7634(00)00016-6 | ref = refColombo2000 | s2cid = 22686204 }}</ref> Numerous species of birds have strong spatial skills, in particular those that cache (store) food. There is evidence that food-caching birds have a larger hippocampus than other types of birds and that damage to the hippocampus causes impairments in spatial memory.<ref>{{cite journal | vauthors = Shettleworth SJ | title = Memory and hippocampal specialization in food-storing birds: challenges for research on comparative cognition | journal = Brain, Behavior and Evolution | volume = 62 | issue = 2 | pages = 108–116 | year = 2003 | pmid = 12937349 | doi = 10.1159/000072441 | ref = refShettleworth2003 | s2cid = 23546600 }}</ref>

===Insects and molluscs===
Some types of [[insect]]s such as [[cockroaches]], and [[molluscs]] such as the [[octopus]], also have strong spatial learning and navigation abilities, but these appear to work differently from the mammalian spatial system, suggesting that there is no common evolutionary origin. [[Mushroom bodies]] in insect brains are associated with learning and memory carried out in the mammalian hippocampus.<ref>{{cite journal | vauthors = Mizunami M, Weibrecht JM, Strausfeld NJ | title = Mushroom bodies of the cockroach: their participation in place memory | journal = The Journal of Comparative Neurology | volume = 402 | issue = 4 | pages = 520–537 | date = December 1998 | pmid = 9862324 | doi = 10.1002/(SICI)1096-9861(19981228)402:4<520::AID-CNE6>3.0.CO;2-K | ref = refMizunami1998 | s2cid = 44384958 }}</ref> The brain of the octopus is arranged in a circle of lobes around the esophagus. The vertical lobe has been shown to be involved in forming long term memory, and is seen to be analogous to the mammalian hippocampus and [[cerebellum]], and also to share some functional features of the mushroom bodies in insects.<ref name="Jacobs">{{cite journal |vauthors=Jacobs RE |title=Diffusion MRI Connections in the Octopus Brain |journal=Exp Neurobiol |volume=31 |issue=1 |pages=17–28 |date=February 2022 |pmid=35256541 |pmc=8907252 |doi=10.5607/en21047 |url=}}</ref><ref name="Richter">{{cite journal |vauthors=Richter JN, Hochner B, Kuba MJ |title=Pull or Push? Octopuses Solve a Puzzle Problem |journal=PLOS ONE |volume=11 |issue=3 |article-number=e0152048 |date=2016 |pmid=27003439 |pmc=4803207 |doi=10.1371/journal.pone.0152048 |doi-access=free |bibcode=2016PLoSO..1152048R |url=}}</ref>

==See also==
* [[Visual short-term memory]]

==Additional images==
<gallery>
File:Hippocampus coronal sections.gif|Hippocampus highlighted in green on coronal [[T1-weighted MRI|T1 MRI images]]
File:Hippocampus sagittal sections.gif|Hippocampus highlighted in green on sagittal [[T1-weighted MRI|T1 MRI images]]
File:Hippocampus transversal sections.gif|Hippocampus highlighted in green on transversal [[T1-weighted MRI|T1 MRI images]]
</gallery>

== References ==
{{Academic peer reviewed|Q=Q43997714|doi-access=free}}
{{reflist|25em}}

== External links ==
{{Spoken Wikipedia|date=2025-09-07|Hippocampus.ogg}}
{{Commons category|Hippocampus (anatomy)|Hippocampus}}
* {{BrainMaps|hippocampus}}
* [http://www.stanford.edu/group/maciverlab/hippocampal.html Diagram of a Hippocampal Brain Slice]
* [http://ccdb.ucsd.edu/sand/main?stype=lite&keyword=hippocampus&Submit=Go&event=display&start=1 Hippocampus – Cell Centered Database]
* [http://www.temporal-lobe.com Temporal-lobe.com An interactive diagram of the rat parahippocampal-hippocampal region]
* {{cite web | url = http://www.brainnav.com/browse?highlight=8d89b5&specid=2 | title = Search Hippocampus on BrainNavigator | archive-url = https://web.archive.org/web/20120309084137/http://www.brainnav.com/browse?highlight=8d89b5&specid=2 | archive-date=2012-03-09 | work = via BrainNavigator }}
* [https://hippocampome.org/php/index.php Hippocampome.org] {{cite journal | vauthors = Wheeler DW, Kopsick JD, Sutton N, Tecuatl C, Komendantov AO, Nadella K, Ascoli GA | title = Hippocampome.org 2.0 is a knowledge base enabling data-driven spiking neural network simulations of rodent hippocampal circuits | journal = eLife | volume = 12 | issue = | date = February 2024 | article-number = RP90597 | pmid = 38345923 | pmc = 10942544 | doi = 10.7554/eLife.90597 | doi-access = free }}
* https://web.archive.org/web/20110722072202/http://web.sc.itc.keio.ac.jp/anatomy/Rauber-Kopsch/web/abb2/png144/440.png

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