Editing Dentate gyrus

{{short description|Region of the hippocampus in the brain}}
{{Use dmy dates|date=September 2020}}
{{Infobox brain
|  Name            = Dentate gyrus
|  Latin           = gyrus dentatus
|  Image           = HippocampalRegions.jpg
|  Caption         = Diagram of [[hippocampal]] regions. DG: Dentate gyrus.
|  Image2          = Gray717.png
|  Caption2        = Coronal section of brain immediately in front of pons. (Label for "Gyrus dentatus" is at bottom center.)
|  IsPartOf        = [[Temporal lobe]]
|  Components      = 
|  Artery          = [[Posterior cerebral artery|Posterior cerebral]]<br/>[[Anterior choroidal artery|Anterior choroidal]]
|  Vein            = 
}}

The '''dentate gyrus''' ('''DG''') is one of the [[hippocampal subfields|subfields]] of the [[hippocampus]], in the [[hippocampal formation]]. The hippocampal formation is located in the [[temporal lobe]] of the [[brain]], and includes the [[hippocampus]] (including CA1 to CA4) subfields, and other subfields including the dentate gyrus, [[subiculum]], and [[presubiculum]].<ref name="Meier2020">{{cite journal |last1=Meier |first1=Kolja |last2=Merseburg |first2=Andrea |last3=Isbrandt |first3=Dirk |last4=Marguet |first4=Stephan Lawrence |last5=Morellini |first5=Fabio |title=Dentate Gyrus Sharp Waves, a Local Field Potential Correlate of Learning in the Dentate Gyrus of Mice |journal=The Journal of Neuroscience |date=9 September 2020 |volume=40 |issue=37 |pages=7105–7118 |doi=10.1523/JNEUROSCI.2275-19.2020|pmid=32817247 |pmc=7480236 }}</ref><ref name="Tuncdemir"/>

The dentate gyrus is part of the [[trisynaptic circuit]], a neural circuit of the hippocampus, thought to contribute to the formation of new [[episodic memory|episodic memories]],<ref name="pmid17765709"/><ref name="pmid19755107">{{Cite journal|vauthors=Saab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F, Mansuy IM, Roder JC | title = NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory. | journal = Neuron | volume = 63 | issue = 5 | pages = 643–56 | year = 2009 | pmid = 19755107 | doi = 10.1016/j.neuron.2009.08.014 | s2cid = 5321020 | doi-access = free }}</ref> the spontaneous exploration of novel environments<ref name="pmid19755107"/> and other functions.<ref name="Scharfman">{{cite book |editor1-last=Scharfman |editor1-first=Helen E. |title=The Dentate Gyrus: A Comprehensive Guide to Structure, Function, and Clinical Implications |date=2011 |publisher=Elsevier |isbn=978-0-08-055175-3 |url=https://www.sciencedirect.com/bookseries/progress-in-brain-research/vol/163/suppl/C }}{{page needed|date=February 2022}}</ref> The dentate gyrus has toothlike projections from which it is named.<ref name="Singh">{{cite book |last1=Singh |first1=Vishram |title=Textbook of Anatomy Volume III |date=2014 |publisher=RELX India |isbn=9788131237274 |page=403 |edition=2nd}}</ref>

The [[subgranular zone]] of the dentate gyrus is one of only two major sites of [[adult neurogenesis]] in the brain, and is found in many [[mammal]]s.<ref name="pmid11406822">{{cite journal | vauthors = Cameron HA, McKay RD | title = Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus | journal = J. Comp. Neurol. | volume = 435 | issue = 4 | pages = 406–17 | date = July 2001 | pmid = 11406822 | doi = 10.1002/cne.1040| s2cid = 15254735 | url = https://zenodo.org/record/1229141 }}</ref> The other main site is the [[subventricular zone]] in the [[ventricular system]]. Other sites  may include  the [[striatum]] and the [[cerebellum]].<ref>{{cite journal |vauthors=Ponti G, Peretto P, Bonfanti L |title=Genesis of neuronal and glial progenitors in the cerebellar cortex of peripuberal and adult rabbits |journal=PLOS ONE |volume=3 |issue=6 |pages=e2366 |year=2008 |pmid=18523645 |pmc=2396292 |doi=10.1371/journal.pone.0002366|bibcode=2008PLoSO...3.2366P |doi-access=free }}</ref><ref>{{cite journal|last1=Ernst|first1=A|last2=Alkass|first2=K|last3=Bernard|first3=S|last4=Salehpour|first4=M|last5=Perl|first5=S|last6=Tisdale|first6=J|last7=Possnert|first7=G|last8=Druid|first8=H|last9=Frisén|first9=J|title=Neurogenesis in the striatum of the adult human brain.|journal=Cell|date=27 February 2014|volume=156|issue=5|pages=1072–83|doi=10.1016/j.cell.2014.01.044|pmid=24561062|doi-access=free}}</ref> However, whether significant neurogenesis takes place in the adult human dentate gyrus has been a matter of debate.<ref name="pmid29513649">{{cite journal | vauthors = Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D, Kelley KW, James D, Mayer S, Chang J, Auguste KI, Chang EF, Gutierrez AJ, Kriegstein AR, Mathern GW, Oldham MC, Huang EJ, Garcia-Verdugo JM, Yang Z, Alvarez-Buylla A |display-authors = 6| title = Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults | journal = Nature | volume = 555 | issue = 7696 | pages = 377–381 | date = March 2018 | pmid = 29513649 | pmc = 6179355 | doi = 10.1038/nature25975 | bibcode=2018Natur.555..377S}}</ref><ref name="pmid29625071">{{cite journal | vauthors = Boldrini M, Fulmore CA, Tartt AN, Simeon LR, Pavlova I, Poposka V, Rosoklija GB, Stankov A, Arango V, Dwork AJ, Hen R, Mann JJ|display-authors = 6 | title = Human Hippocampal Neurogenesis Persists throughout Aging | journal = Cell Stem Cell | volume = 22 | issue = 4 | pages = 589–599.e5 | date = April 2018 | pmid = 29625071 |pmc = 5957089 | doi = 10.1016/j.stem.2018.03.015 }}</ref><ref name="Abbott">{{cite journal |last1=Abbott |first1=Louise C. |last2=Nigussie |first2=Fikru |title=Adult neurogenesis in the mammalian dentate gyrus |journal=Anatomia, Histologia, Embryologia |date=January 2020 |volume=49 |issue=1 |pages=3–16 |doi=10.1111/ahe.12496 |pmid=31568602 |doi-access= |s2cid=203622372 }}</ref><ref name="Tuncdemir"/><ref>{{Cite journal |last1=Zhou |first1=Yi |last2=Su |first2=Yijing |last3=Li |first3=Shiying |last4=Kennedy |first4=Benjamin C. |last5=Zhang |first5=Daniel Y. |last6=Bond |first6=Allison M. |last7=Sun |first7=Yusha |last8=Jacob |first8=Fadi |last9=Lu |first9=Lu |last10=Hu |first10=Peng |last11=Viaene |first11=Angela N. |last12=Helbig |first12=Ingo |last13=Kessler |first13=Sudha K. |last14=Lucas |first14=Timothy |last15=Salinas |first15=Ryan D. |date=July 2022 |title=Molecular landscapes of human hippocampal immature neurons across lifespan |journal=Nature |volume=607 |issue=7919 |pages=527–533 |doi=10.1038/s41586-022-04912-w |issn=1476-4687 |pmc=9316413 |pmid=35794479|bibcode=2022Natur.607..527Z }}</ref>

==Structure==
[[File:Cerebral Gyri - Medial Surface2.png|thumb|Location of the dentate gyrus and relations to other structures.]]

The dentate gyrus, like the hippocampus, consists of [[archicortex|three distinct layers]]: an outer molecular layer, a middle granule cell layer, and an inner polymorphic layer.<ref>{{cite journal |last1=Treves |first1=A. |last2=Tashiro |first2=A. |last3=Witter |first3=M.P. |last4=Moser |first4=E.I. |title=What is the mammalian dentate gyrus good for? |journal=Neuroscience |date=July 2008 |volume=154 |issue=4 |pages=1155–1172 |doi=10.1016/j.neuroscience.2008.04.073 |pmid=18554812 |s2cid=14710031 }}</ref> The polymorphic layer is also the '''hilus''' of the dentate gyrus (originally named as CA4, the junction of the hippocampus and dentate gyrus).<ref name="Scharfman2">{{cite journal |last1=Scharfman |first1=Helen E. |title=The enigmatic mossy cell of the dentate gyrus |journal=Nature Reviews Neuroscience |date=September 2016 |volume=17 |issue=9 |pages=562–575 |doi=10.1038/nrn.2016.87 |pmid=27466143 |pmc=5369357 }}</ref><ref name="Haines">{{cite book |last1=Haines |first1=D |last2=Mihailoff |first2=G |title=Fundamental neuroscience for basic and clinical applications |date=2018 |isbn=9780323396325 |page=461 |publisher=Elsevier |edition=Fifth}}</ref> (In the hippocampus the outer layer is the molecular layer, the middle layer is the pyramidal layer, and the inner layer the stratum oriens.) Sometimes the molecular layer and the granule layer are referred to as the '''fascia dentata''', that encloses the hilus or polymorphic layer.<ref name="MorrisAmaral2024">{{cite book |last1=Morris |first1=Richard |last2=Amaral |first2=David |title=The Hippocampus Book |date=2024 |publisher=Oxford University Press Inc |location=New York |isbn=9780190065324 |page=52}}</ref><ref name="Hevner">{{cite journal |last1=Hevner |first1=RF |title=Evolution of the mammalian dentate gyrus. |journal=The Journal of Comparative Neurology |date=15 February 2016 |volume=524 |issue=3 |pages=578–94 |doi=10.1002/cne.23851 |pmid=26179319|pmc=4706817 }}</ref>

The granule layer is between the overlying molecular layer and the underlying hilus (polymorphic layer).<ref name="Tuncdemir">{{cite journal |last1=Tuncdemir |first1=Sebnem Nur |last2=Lacefield |first2=Clay Orion |last3=Hen |first3=Rene |title=Contributions of adult neurogenesis to dentate gyrus network activity and computations |journal=Behavioural Brain Research |date=November 2019 |volume=374 |pages=112112 |doi=10.1016/j.bbr.2019.112112 |pmid=31377252 |pmc=6724741 }}</ref>
The [[granule cell]]s of the granule layer project their axons known as [[mossy fiber (hippocampus)|mossy fiber]]s to make excitatory [[synapse]]s on the [[dendrite]]s of CA3 [[pyramidal neuron]]s. The granule cells are tightly packed together in a laminated manner that dampens the excitability of neurons.<ref name="Nadler">{{cite journal |last1=Nadler |first1=J. Victor |title=The recurrent mossy fiber pathway of the epileptic brain |journal=Neurochemical Research |date=2003 |volume=28 |issue=11 |pages=1649–1658 |doi=10.1023/a:1026004904199 |pmid=14584819 |s2cid=2566342 }}</ref>

Some of the basal dendrites of the granule cells curve up into the molecular layer. Most basal dendrites enter the hilus. These hilar dendrites are shorter and thinner, and have fewer side branches.<ref name="Seress">{{cite journal |last1=Seress |first1=László |last2=Mrzljak |first2=Ladislav |title=Basal dendrites of granule cells are normal features of the fetal and adult dentate gyrus of both monkey and human hippocampal formations |journal=Brain Research |date=March 1987 |volume=405 |issue=1 |pages=169–174 |doi=10.1016/0006-8993(87)91003-1 |pmid=3567591 |s2cid=23358962 }}</ref>

A second excitatory cell type in the hilus is the '''mossy cell''',<ref name="Scharfman2"/> which projects its axons widely along the septotemporal axis (running from the [[septal area]] to the [[temporal lobe]]) with the ipsilateral projection skipping the first 1–2&nbsp;mm near the cell bodies,<ref>{{cite journal | vauthors = Amaral DG, Witter MP | year = 1989 | title = The three-dimensional organization of the hippocampal formation: a review of anatomical data | journal = Neuroscience | volume = 31 | issue = 3| pages = 571–591 | doi = 10.1016/0306-4522(89)90424-7 | pmid = 2687721 | s2cid = 28430607 }}</ref> an unusual configuration, hypothesized to prepare a set of cell assemblies in CA3 for a data retrieval role, by randomizing their cell distribution.<ref>{{cite journal | vauthors = Legéndy CR | year = 2017 | title = On the 'data stirring' role of the dentate gyrus of the hippocampus | journal = Reviews in the Neurosciences | volume = 28 | issue = 6| pages = 599–615 | doi = 10.1515/revneuro-2016-0080 | pmid = 28593904 | s2cid = 3716652 }}</ref>

Between the hilus and the granule cell layer is a region called the [[subgranular zone]] which is a site of adult [[adult neurogenesis|neurogenesis]].<ref name="Tuncdemir"/>

The anteromedial continuation of the dentate gyrus is called the '''tail of the dentate gyrus''', or the '''band of Giacomini'''. Most of the dentate gyrus is not exposed on the surface of the brain but the band of Giacomini is visible, and makes an important landmark of the inferior surface of the [[uncus]].<ref name="Elgendy">{{cite web |last1=Elgendy |first1=Azza |title=Band of Giacomini {{!}} Radiology Reference Article {{!}} Radiopaedia.org |url=https://radiopaedia.org/articles/band-of-giacomini?lang=gb |website=Radiopaedia |date=27 January 2015 |access-date=17 October 2019}}</ref>

===Trisynaptic circuit===
The [[trisynaptic circuit]] consists of excitatory cells (mostly [[stellate cell]]s) in [[Entorhinal cortex#Connections|layer II]] of the [[entorhinal cortex]], projecting to the granule cell layer of the dentate gyrus via the [[perforant path]].<ref name="Sinauer Associates">{{cite book|last1=Blumenfeld|first1=Hal|title=Neuroanatomy through clinical cases|date=2010|publisher=Sinauer Associates|location=Sunderland, Mass.|isbn=978-0878936137|edition= 2nd}}</ref><ref name="Senzai">{{cite journal |last1=Senzai |first1=Yuta |title=Function of local circuits in the hippocampal dentate gyrus-CA3 system |journal=Neuroscience Research |date=March 2019 |volume=140 |pages=43–52 |doi=10.1016/j.neures.2018.11.003 |pmid=30408501 |s2cid=53220907 }}</ref> The dentate gyrus receives no direct inputs from other cortical structures.<ref>{{Cite book|author=Nolte, John |title=The Human Brain: An Introduction to Its Functional Neuroanatomy |edition= fifth|year=2002 |pages=570–573}}</ref> The perforant path is divided into the medial and lateral perforant paths, generated, respectively, at the medial and lateral portions of the entorhinal cortex. The medial perforant path synapses onto the proximal dendritic area of the granule cells, whereas the lateral perforant path does so onto their distal dendrites. Most lateral views of the dentate gyrus may appear to suggest a structure consisting of just one entity, but medial movement may provide evidence of the ventral and dorsal parts of the dentate gyrus.<ref>{{cite journal|author1=Rachel A. Dalley |author2=Lydia L. Ng |author3=Angela L. Guillozet-Bongaarts |journal=Nature Precedings|title=Dentate Gyrus|doi=10.1038/npre.2008.2095.1|year=2008 |doi-access=free }}</ref> The axons of the granule cells, called mossy fibres, make excitatory synaptic connections with the pyramidal cells of CA3 and CA1.<ref name="Senzai"/>

==Development==
The granule cells in the dentate gyrus are distinguished by their late time of formation during brain development.  In rats, approximately 85% of the granule cells are generated after birth.<ref name="pmid4430737">{{cite journal | vauthors = Bayer SA, Altman J | title = Hippocampal development in the rat: cytogenesis and morphogenesis examined with autoradiography and low-level X-irradiation | journal = J. Comp. Neurol. | volume = 158 | issue = 1 | pages = 55–79 | date = November 1974 | pmid = 4430737 | doi = 10.1002/cne.901580105 | s2cid = 17968282 }}</ref> In humans, it is estimated that granule cells begin to be generated during gestation weeks 10.5 to 11, and continue being generated during the second and third trimesters, after birth and all the way into adulthood.<ref>{{Cite book| vauthors = Bayer SA, Altman J | title = The Human Brain During The Early First Trimester | volume = 5 Atlas of Human Central Nervous System Development | year = 2008|at = Appendix, p. 497}}</ref><ref>{{Cite journal |vauthors=Eriksson PS, Perfilieva E, Björk-Eriksson T, etal |title=Neurogenesis in the adult human hippocampus |journal=Nat. Med. |volume=4 |issue=11 |pages=1313–7 |date=November 1998 |pmid=9809557 |doi=10.1038/3305 |doi-access=free }}</ref> The germinal sources of granule cells and their migration pathways<ref name="pmid2262596">{{cite journal | vauthors = Altman J, Bayer SA | title = Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods | journal = J. Comp. Neurol. | volume = 301 | issue = 3 | pages = 365–81 | date = November 1990 | pmid = 2262596 | doi = 10.1002/cne.903010304 | s2cid = 7425653 }}</ref> have been studied during rat brain development. The oldest granule cells are generated in a specific region of the hippocampal neuroepithelium and migrate into the primordial dentate gyrus around embryonic days (E) 17/18, and then settle as the outermost cells in the forming granular layer. Next, dentate precursor cells move out of this same area of the hippocampal neuroepithelium and, retaining their mitotic capacity, invade the hilus (core) of the forming dentate gyrus. This dispersed germinal matrix is the source of granule cells from that point on.  The newly generated granule cells accumulate under the older cells that began to settle in the granular layer. As more granule cells are produced, the layer thickens and the cells are stacked up according to age—the oldest being the most superficial and the youngest being deeper.<ref name="pmid5838955">{{cite journal | vauthors = Angevine JB | title = Time of neuron origin in the hippocampal region. An autoradiographic study in the mouse | journal = Exp Neurol Suppl | issue =Suppl 2 | pages = Suppl 2:1–70 | date = October 1965 | pmid = 5838955 }}</ref> The granule cell precursors remain in a subgranular zone that becomes progressively thinner as the dentate gyrus grows, but these precursor cells are retained in adult rats.  These sparsely scattered cells constantly generate granule cell neurons,<ref name="pmid7079742">{{cite journal | vauthors = Bayer SA, Yackel JW, Puri PS | title = Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life | journal = Science | volume = 216 | issue = 4548 | pages = 890–2 | date = May 1982 | pmid = 7079742 |bibcode = 1982Sci...216..890B |doi = 10.1126/science.7079742 }}</ref><ref name="pmid7095040">{{cite journal | vauthors = Bayer SA | title = Changes in the total number of dentate granule cells in juvenile and adult rats: a correlated volumetric and 3H-thymidine autoradiographic study | journal = Exp Brain Res | volume = 46 | issue = 3 | pages = 315–23 | date = 1982 | pmid = 7095040 | doi = 10.1007/bf00238626| s2cid = 18663323 }}</ref> which add to the total population. There are a variety of other differences in the rat, monkey and human dentate gyrus. The granule cells only have apical dendrites in the rat. But in the monkey and human, many granule cells also have basal dendrites.<ref name="pmid17765709">{{cite book |doi=10.1016/S0079-6123(07)63001-5 |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 |year=2007 |last1=Amaral |first1=David G. |last2=Scharfman |first2=Helen E. |last3=Lavenex |first3=Pierre |volume=163 |pages=3–790 |pmid=17765709 |pmc=2492885 |isbn=9780444530158 }}</ref>

==Function==
[[File:Doublecortin expression-2.png|thumb|upright=1.6|The [[subgranular zone]] (in rat brain). (A) Regions of the dentate gyrus: the hilus, subgranular zone (sgz), [[granule cell]] layer (GCL), and molecular layer (ML). Cells were stained for [[doublecortin]] (DCX). (B) Closeup of subgranular zone, located between the hilus and GCL,<ref name="Oomen">{{cite journal |last1=Oomen |first1=Charlotte A. |last2=Girardi |first2=Carlos E. N. |last3=Cahyadi |first3=Rudy |last4=Verbeek |first4=Eva C. |last5=Krugers |first5=Harm |last6=Joëls |first6=Marian |last7=Lucassen |first7=Paul J. |title=Opposite Effects of Early Maternal Deprivation on Neurogenesis in Male versus Female Rats |journal=PLOS ONE |date=29 January 2009 |volume=4 |issue=1 |pages=e3675 |doi=10.1371/journal.pone.0003675 |pmid=19180242 |pmc=2629844 |bibcode=2009PLoSO...4.3675O |doi-access=free }}</ref> a site of [[adult neurogenesis]].]]

[[File:Proliferating cells in the dentate gyrus (crop).jpg|thumb|Phenotypes of proliferating cells in the dentate gyrus. A fragment of [[:commons:File:Phenotypes of proliferating cells in the Rostral Migratory Stream and Dentate Gyrus.jpg|an illustration]] from Faiz et al., 2005.<ref name="pmid15826306">{{Cite journal|vauthors=Faiz M, Acarin L, Castellano B, Gonzalez B |title=Proliferation dynamics of germinative zone cells in the intact and excitotoxically lesioned postnatal rat brain |journal=[[BMC Neurosci]] |volume=6 |issue= 1|page=26 |year=2005 |pmid=15826306 |pmc=1087489 |doi=10.1186/1471-2202-6-26 |doi-access=free }}</ref>]]

The dentate gyrus is thought to contribute to the formation of memories, and to play a role in [[depression (mood)|depression]].

The role of the hippocampus in learning and memory has been studied for many decades particularly since the late 1950s, following the results of surgery, in an American male, to remove most of the hippocampus.<ref name=carey>{{cite news|url=https://www.nytimes.com/2008/12/05/us/05hm.html | title=H. M., an Unforgettable Amnesiac, Dies at 82  | author=Benedict Carey | newspaper=[[The New York Times]]|quote=In 1953, he underwent an experimental brain operation in Hartford to correct a seizure disorder, only to emerge from it fundamentally and irreparably changed. He developed a syndrome neurologists call profound amnesia. He had lost the ability to form new declarative memories. | date=4 December 2008 | access-date=5 December 2008| author-link=Benedict Carey }}</ref> It remains unclear how the hippocampus enables new memory formation, but one process, called [[long term potentiation]] (LTP), occurs in this brain region.<ref name="Principles of neural science"/> LTP involves long-lasting strengthening of synaptic connections after repeated stimulation.<ref name="Sinauer Associates"/> While the dentate gyrus shows LTP, it is also one of the few regions of the mammalian brain where [[adult neurogenesis]] (the formation of new neurons) takes place. Some studies hypothesize that new memories could preferentially use newly formed [[granule cells]] of the dentate gyrus, providing a potential mechanism for distinguishing multiple instances of similar events or multiple visits to the same location.<ref name="Nakashiba">{{cite journal | vauthors = Nakashiba T, Cushman JD, Pelkey KA, Renaudineau S, Buhl DL, McHugh TJ, Rodriguez Barrera V, Chittajallu R, Iwamoto KS, McBain CJ, Fanselow MS, Tonegawa S |display-authors = 6 | title = Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion | journal = Cell | volume = 149 | issue = 1 | pages = 188–201 | date = March 2012 | pmid = 22365813 | pmc = 3319279 | doi = 10.1016/j.cell.2012.01.046 }}</ref> Correspondingly, it has been proposed that the immature, newborn granule cells are receptive to form new synaptic connections with the [[axons]] arriving from the layer II of the [[entorhinal cortex]], this way a particular new constellation of events is remembered as an [[episodic memory]] by first associating the events in the young granule cells that have the appropriate, permissive age.<ref>{{cite journal | vauthors = Kovács KA | title = Episodic Memories: How do the Hippocampus and the Entorhinal Ring Attractors Cooperate to Create Them? | journal = Frontiers in Systems Neuroscience | volume = 14 | pages = 68 | date = September 2020 | doi = 10.3389/fnsys.2020.559186 | pmid = 33013334 | pmc = 7511719 | doi-access = free }}</ref> This concept is reinforced by the fact that increased neurogenesis is associated with improved spatial memory in rodents, as seen through performance in a maze.<ref>{{cite web |url=http://www.ars.usda.gov/is/ar/archive/aug07/aging0807.htm. |title="Food and the Aging Mind". First in a Series: Nutrition and Brain Function |vauthors=Bliss RM|date=August 2007 |website=USDA |publisher=USDA.gov |access-date= 27 February 2010}}</ref>

The dentate gyrus is known to serve as a pre-processing unit. While the CA3 subfield is involved in encoding, storage, and retrieval of memory, the dentate gyrus is important in [[Place cell#Pattern separation|pattern separation]].<ref name="Senzai" /> When information enters via the perforant path, the dentate gyrus separates very similar information into distinct and unique details.<ref name="Frontiers"/><ref>{{cite journal |last1=Lamothe-Molina |first1=Paul J. |last2=Franzelin |first2=Andreas |last3=Auksutat |first3=Lea |last4=Laprell |first4=Laura |last5=Alhbeck |first5=Joachim |last6=Kneussel |first6=Matthias |last7=Engel |first7=Andreas K. |last8=Morellini |first8=Fabio |last9=Oertner |first9=Thomas G. |title=cFos ensembles in the dentate gyrus rapidly segregate over time and do not form a stable map of space |date=31 August 2020 |doi=10.1101/2020.08.29.273391 |s2cid=221510080 |url=https://www.biorxiv.org/content/biorxiv/early/2020/08/31/2020.08.29.273391.full.pdf }}</ref> This ensures that new memories are encoded separately without input from previously stored memories of similar feature,<ref name="Tuncdemir"/> and prepares the relevant data for storage in the CA3 region.<ref name="Frontiers">{{cite journal |last1=Jonas |first1=Peter |last2=Lisman |first2=John |title=Structure, function, and plasticity of hippocampal dentate gyrus microcircuits |journal=Frontiers in Neural Circuits |date=10 September 2014 |volume=8 |page=107 |doi=10.3389/fncir.2014.00107 |pmid=25309334 |pmc=4159971 |doi-access=free }}</ref> Pattern separation gives the ability to differentiate one memory from other stored memories.<ref name="Moser">{{cite journal |last1=Moser |first1=Edvard I. |last2=Kropff |first2=Emilio |last3=Moser |first3=May-Britt |title=Place Cells, Grid Cells, and the Brain's Spatial Representation System |journal=Annual Review of Neuroscience |date=1 July 2008 |volume=31 |issue=1 |pages=69–89 |doi=10.1146/annurev.neuro.31.061307.090723 |pmid=18284371 }}</ref> Pattern separation begins in the dentate gyrus. Granule cells in the dentate gyrus process sensory information using [[competitive learning]], and relay a preliminary representation to form [[place field]]s.<ref name="Rolls">{{cite journal |last1=Rolls |first1=Edmund T. |title=The mechanisms for pattern completion and pattern separation in the hippocampus |journal=Frontiers in Systems Neuroscience |date=2013 |volume=7 |page=74 |doi=10.3389/fnsys.2013.00074 |pmid=24198767 |pmc=3812781 |doi-access=free }}</ref> Place fields are extremely specific, as they are capable of remapping and adjusting firing rates in response to subtle sensory signal changes. This specificity is critical for pattern separation, as it distinguishes memories from one another.<ref name="Moser"/>

The dentate gyrus shows a specific form of [[Neuroplasticity|neural plasticity]] resulting from the ongoing integration of [[neurogenesis|newly formed]] excitatory granule cells.<ref name="Tuncdemir"/>

==Clinical significance==
===Memory===
One of the most prominent early cases of [[anterograde amnesia]] (inability to form new memories) linking the hippocampus to memory formation was the case of [[Henry Molaison]] (anonymously known as Patient H.M. until his death in 2008).<ref name="Principles of neural science">{{cite book|vauthors = Kandel ER, Schwartz J, Jessell T, Siegelbaum S, Hudspeth AJ|title=Principles of neural science|date=2013|publisher=McGraw Hill Professional|isbn=978-0-07-139011-8|edition= 5th}}</ref> His [[epilepsy]] was treated with surgical removal of the hippocampus from both hemispheres, as well as some surrounding tissue. This targeted brain tissue removal left Mr. Molaison with an inability to form new memories, and the hippocampus has been thought critical to memory formation since that time, though the processes involved are unclear.<ref name="Principles of neural science"/>

===Stress and depression===
The dentate gyrus may also have a functional role in stress and depression. For instance, in the rat, neurogenesis has been found to increase in response to chronic treatment with [[antidepressant]]s.<ref name="Malberg">{{cite journal | vauthors = Malberg JE, Eisch AJ, Nestler EJ, Duman RS | title = Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus | journal = J. Neurosci. | volume = 20 | issue = 24 | pages = 9104–10 | date = December 2000 | pmid = 11124987| pmc = 6773038 | doi = 10.1523/JNEUROSCI.20-24-09104.2000 }}</ref> The physiological effects of stress, often characterized by release of [[glucocorticoid]]s such as [[cortisol]], as well as activation of the [[sympathetic nervous system]] (a division of the [[autonomic nervous system]]), have been shown to inhibit the process of neurogenesis in primates.<ref name="Gould">{{cite journal | vauthors = Gould E, Tanapat P, McEwen BS, Flügge G, Fuchs E | title = Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 6 | pages = 3168–71 | date = March 1998 | pmid = 9501234 | pmc = 19713 | doi = 10.1073/pnas.95.6.3168| bibcode = 1998PNAS...95.3168G| doi-access = free }}</ref> Both endogenous and exogenous glucocorticoids are known to cause psychosis and [[Clinical depression|depression]],<ref name="Jacobs">{{cite journal | vauthors = Jacobs BL, van Praag H, Gage FH | title = Adult brain neurogenesis and psychiatry: a novel theory of depression | journal = Mol. Psychiatry | volume = 5 | issue = 3 | pages = 262–9 | date = May 2000 | pmid = 10889528 | doi = 10.1038/sj.mp.4000712| doi-access = free }}</ref> implying that neurogenesis in the dentate gyrus may play an important role in modulating symptoms of stress and depression.<ref name="Surget">{{cite journal | vauthors = Surget A, Tanti A, Leonardo ED, Laugeray A, Rainer Q, Touma C, Palme R, Griebel G, Ibarguen-Vargas Y, Hen R, Belzung C | title = Antidepressants recruit new neurons to improve stress response regulation | journal = Mol. Psychiatry | volume = 16 | issue = 12 | pages = 1177–88 | date = December 2011 | pmid = 21537331 | pmc = 3223314 | doi = 10.1038/mp.2011.48 }}</ref>

===Blood sugar===
Studies by researchers at [[Columbia University Medical Center]] indicate that [[Blood sugar regulation|poor glucose control]] can lead to deleterious effects on the dentate gyrus, resulting in memory decline.<ref>{{cite news |url=https://www.nytimes.com/2009/01/01/health/31memory.html?_r=1&em=&pagewanted=print |title=Blood Sugar Control Linked to Memory Decline, Study Says |work=The New York Times |date= 1 January 2009 |access-date=2011-03-13}}</ref>

===Other===
Some evidence seen in the [[mouse]] suggests that neurogenesis in the dentate gyrus increases in response to [[exercise|aerobic exercise]].<ref>{{cite journal|last=Praag|first=H|year=1999|title=Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus|journal=Nature Neuroscience|volume=2|pages=266–270|doi=10.1038/6368|pmid=10195220|issue=3|s2cid=7170664}}</ref> Several experiments have shown neurogenesis (the development of nerve tissues) often increases in the dentate gyrus of adult rodents when they are exposed to an enriched environment.<ref name="pmid9087407">{{cite journal | vauthors = Kempermann G, Kuhn HG, Gage FH | title = More hippocampal neurons in adult mice living in an enriched environment | journal = Nature | volume = 386 | issue = 6624 | pages = 493–5 | date = April 1997 | pmid = 9087407 | doi = 10.1038/386493a0 |bibcode = 1997Natur.386..493K | s2cid = 4281128 }}</ref><ref name="pmid15834963">{{cite journal | vauthors = Eadie BD, Redila VA, Christie BR | title = Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density | journal = J. Comp. Neurol. | volume = 486 | issue = 1 | pages = 39–47 | date = May 2005 | pmid = 15834963 | doi = 10.1002/cne.20493 | hdl = 2429/15467 | s2cid = 8386870 | hdl-access = free }}</ref>

===Spatial behavior===
Studies have shown that after having about 90% of their dentate gyrus cells destroyed, rats had extreme difficulty in maneuvering through a maze they had previously navigated. When being tested a number of times to see whether they could learn a maze, the results showed that the rats did not improve at all, indicating that their working memories were severely impaired. Rats had trouble with place strategies because they could not consolidate learned information about a maze into their working memory, and, thus, could not remember it when maneuvering through the same maze in a later trial. Every time a rat entered the maze, the rat behaved as if it was seeing the maze for the first time.<ref name="pmid19375476">{{cite journal | vauthors = Xavier GF, Costa VC | title = Dentate gyrus and spatial behaviour | journal = Prog. Neuropsychopharmacol. Biol. Psychiatry | volume = 33 | issue = 5 | pages = 762–73 | date = August 2009 | pmid = 19375476 | doi = 10.1016/j.pnpbp.2009.03.036 | s2cid = 1115081 | doi-access = free }}</ref>

===DNA double-strand breaks===

Exploration of a novel environment, a natural behavior of young and adult wild-type mice, causes [[double-strand breaks]] (DSBs) in their neurons.<ref name = Suberbielle2013>{{cite journal |vauthors=Suberbielle E, Sanchez PE, Kravitz AV, Wang X, Ho K, Eilertson K, Devidze N, Kreitzer AC, Mucke L |title=Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β |journal=Nat Neurosci |volume=16 |issue=5 |pages=613–21 |date=May 2013 |pmid=23525040 |pmc=3637871 |doi=10.1038/nn.3356 |url=}}</ref> DSBs occur in multiple brain regions and are most frequent in the dentate gyrus which is involved in learning and memory.<ref name = Suberbielle2013/>  These breaks are transient, and are repaired within 24 hours.<ref name = Suberbielle2013/>

==References==
{{Reflist}}

==External links==
{{Commons category|Dentate gyrus}}
* [https://web.archive.org/web/20051216215225/http://www.psycheducation.org/mechanism/images/Dentate.htm Slide] at psycheducation.org
* {{BrainMaps|Dentate%20gyrus|Dentate gyrus}}
* {{cite journal | doi = 10.1126/science.1140263 | pmid=17556551 | volume=317 | issue=5834 | title=Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network | year=2007 | journal=Science | pages=94–99 | vauthors=McHugh TJ| bibcode=2007Sci...317...94M | s2cid=18548 }} The source of ''[[déjà vu]]''.
* [https://web.archive.org/web/20141107191652/https://www.neuinfo.org/mynif/search.php?q=Dentate%20Gyrus&t=data&s=cover&b=0&r=20 NIF Search—Dentate Gyrus] via the [[Neuroscience Information Framework]]
* [http://neurondevelopment.org See Altman and Bayer's work on dentate gyrus development and adult neurogenesis]
* {{cite book |doi=10.1016/S0079-6123(07)63001-5 |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 |year=2007 |last1=Amaral |first1=David G. |last2=Scharfman |first2=Helen E. |last3=Lavenex |first3=Pierre |volume=163 |pages=3–790 |pmid=17765709 |pmc=2492885 |isbn=9780444530158 }}

{{Hippocampal formation}}
{{Cerebral cortex}}
{{Authority control}}

{{DEFAULTSORT:Dentate Gyrus}}
[[Category:Gyri]]
[[Category:Hippocampus (brain)]]