Neural - Hippocampus Development

From Embryology
Embryology - 20 Jun 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)


Historic hippocampus
Adult hippocampus structure

Recent studies have shown that secondary brain vesicle (telencephalon) dorsomedial region described as the "cortical hem" is involved with hippocampus development.[1] The cortical hem is the source for 2 patterning signals; Wingless-related (WNT) and bone morphogenetic protein (BMP).

The adult hippocampus is associated with memory (contextual and working), emotional reactivity and the hypothalamus‎-pituitary-adrenal (HPA) axis function.

Neural development is one of the earliest systems to begin and the last to be completed after birth. This development generates the most complex structure within the embryo and the long time period of development means in utero insult during pregnancy may have consequences to development of the nervous system.

The early central nervous system begins as a simple neural plate that folds to form a groove then tube, open initially at each end. Failure of these opening to close contributes a major class of neural abnormalities (neural tube defects).

Within the neural tube stem cells generate the 2 major classes of cells that make the majority of the nervous system : neurons and glia. Both these classes of cells differentiate into many different types generated with highly specialized functions and shapes. This section covers the establishment of neural populations, the inductive influences of surrounding tissues and the sequential generation of neurons establishing the layered structure seen in the brain and spinal cord.

Neural Links: ectoderm | neural | neural crest | ventricular | sensory | Stage 22 | gliogenesis | neural fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | neural abnormalities | folic acid | iodine deficiency | Fetal Alcohol Syndrome | neural postnatal | neural examination | Histology | Historic Neural | Category:Neural
Neural Parts: neural | prosencephalon | telencephalon cerebrum | amygdala | hippocampus | basal ganglia | diencephalon | epithalamus | thalamus | hypothalamus‎ | pituitary | pineal | mesencephalon | tectum | rhombencephalon | metencephalon | pons | cerebellum | myelencephalon | medulla oblongata | spinal cord | neural vascular | ventricular | lateral ventricles | third ventricle | cerebral aqueduct | fourth ventricle | central canal | meninges | Category:Ventricular System | Category:Neural

Some Recent Findings

  • Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults[2] "New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. ...In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans."
  • Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment[3] "The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. ...Moreover, behavioral and functional studies demonstrated that POMC-Notch1-/- mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus." Notch
More recent papers
Mark Hill.jpg
PubMed logo.gif

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

  • This search now requires a manual link as the original PubMed extension has been disabled.
  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
  • References also appear on this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Hippocampus Development | Hippocampus Embryology | dentate gyrus development |

Older papers
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Evolution of the mammalian dentate gyrus[4] "The dentate gyrus (DG), a part of the hippocampal formation, has important functions in learning, memory, and adult neurogenesis. Compared with homologous areas in sauropsids (birds and reptiles), the mammalian DG is larger and exhibits qualitatively different phenotypes: 1) folded (C- or V-shaped) granule neuron layer, concave toward the hilus and delimited by a hippocampal fissure; 2) nonperiventricular adult neurogenesis; and 3) prolonged ontogeny, involving extensive abventricular (basal) migration and proliferation of neural stem and progenitor cells (NSPCs). Although gaps remain, available data indicate that these DG traits are present in all orders of mammals, including monotremes and marsupials. The exception is Cetacea (whales, dolphins, and porpoises), in which DG size, convolution, and adult neurogenesis have undergone evolutionary regression." See also[5][6]
  • Hopx distinguishes hippocampal from lateral ventricle neural stem cells[7] "In the adult dentate gyrus (DG) and in the proliferative zone lining the lateral ventricle (LV-PZ), radial glia-like (RGL) cells are neural stem cells (NSCs) that generate granule neurons. A number of molecular markers including glial fibrillary acidic protein (GFAP), Sox2 and nestin, can identify quiescent NSCs in these two niches. ...These findings establish that Hopx expression distinguishes NSCs of the DG from those of the LV-PZ, and suggest that Hopx potentially regulates hippocampal neurogenesis by modulating Notch singling." Notch | Stem Cells | OMIM 607275 (Note Hopx also expressed in cardiomyoblast intermediate committed to cardiomyocyte fate)
  • Neurogenesis in the Septal and Temporal part of the Adult Rat Dentate Gyrus[8] "Newborn neurons migration from the neurogenic subgranular zone to the inner granular cell layer and expression of glutamate NMDA and AMPA receptors were also studied. BrdU immunocytochemistry revealed comparatively higher numbers of BrdU+ cells in the septal part, but stereological analysis of newborn and total granule cells showed an identical ratio in the two parts, indicating an equivalent neurogenic ability, and a common topographical pattern along each part's longitudinal and transverse axis. Similarly, both parts exhibited extremely low levels of newborn glial and apoptotic cells. However, despite the initially equal division rate and pattern of the septal and temporal proliferating cells, their later proliferative profile diverged in the two parts. Dynamic differences in the differentiation, migration and maturation process of the two BrdU-incorporating subpopulations of newborn neurons were also detected, along with differences in their survival pattern." rat
  • 2014 Nobel Prize in Physiology or Medicine John O´Keefe, May-Britt Moser and Edvard I. Moser - for their discoveries of cells that constitute a positioning system in the brain (More? Nobel Press Release)
  • Development of laminar organization of the fetal cerebrum[9]"Heads of 131 fetal specimens of 14-40 weeks gestational age (GA) were scanned by 3.0T MRI. Eleven fetal specimens of 14-27 weeks GA were scanned by 7.0T MRI. On T(1)-weighted 3.0T MRI, layers could be visualized at 14 weeks GA and appeared clearer after 18 weeks GA. On 7.0T MRI, four zones could be recognized at 14 weeks GA. During 15-22 weeks GA, when laminar organization appeared typical, seven layers including the periventricular zone and external capsule fibers could be differentiated, which corresponded to seven zones in histological stained sections. At 23-28 weeks GA, laminar organization appeared less typical, and borderlines among them appeared obscured. After 30 weeks GA, it disappeared and turned into mature-like structures. The developing lamination appeared the most distinguishable at the parieto-occipital part of brain and peripheral regions of the hippocampus. The migrating thalamocortical afferents were probably delineated as a high signal layer located at the lower, middle, and upper part of the subplate zone at 16-28 weeks GA on T(1)-weighted 3.0T MRI."

Development Overview

Neuralation begins at the trilaminar embryo with formation of the notochord and somites, both of which underly the ectoderm and do not contribute to the nervous system, but are involved with patterning its initial formation. The central portion of the ectoderm then forms the neural plate that folds to form the neural tube, that will eventually form the entire central nervous system.

Early developmental sequence: Epiblast - Ectoderm - Neural Plate - Neural groove and Neural Crest - Neural Tube and Neural Crest

Neural Tube Development
Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
week 3 week 4 week 5 adult
neural plate
neural groove
neural tube

prosencephalon (forebrain) telencephalon Rhinencephalon, Amygdala, hippocampus, cerebrum (cortex), hypothalamus‎, pituitary | Basal Ganglia, lateral ventricles
diencephalon epithalamus, thalamus, Subthalamus, pineal, posterior commissure, pretectum, third ventricle
mesencephalon (midbrain) mesencephalon tectum, Cerebral peduncle, cerebral aqueduct, pons
rhombencephalon (hindbrain) metencephalon cerebellum
myelencephalon medulla oblongata, isthmus
spinal cord, pyramidal decussation, central canal

Early Brain Vesicles

Primary Vesicles

CNS primary vesicles.jpg

Secondary Vesicles

CNS secondary vesicles.jpg

Human Hippocampus Development

Neural - Human hippocampus marker expression.jpg

Human and rodent hippocampus developmental markers.[10]


The following data (GA gestational age weeks) is from an imaging study of the human fetal hippocampus.[11]

  • 13 to 14 weeks - unfolded hippocampus, on the medial surface of the temporal lobe, surrounds a widely open hippocampal sulcus (hippocampal fissure)
  • 15 to 16 weeks - dentate gyrus and cornu ammonis have started to infold. The hippocampal sulcus remains open. The parahippocampal gyrus is larger and more medially positioned. The CA1, CA2, and CA3 fields of the cornu ammonis are arranged linearly. The dentate gyrus has a narrow U shape.
  • 18 to 20 weeks - fetal hippocampus begins to resemble the adult hippocampus. The dentate gyrus and cornu ammonis have folded into the temporal lobe. The hippocampus and subiculum approximate each other across a narrow hippocampal sulcus. The CA1-3 fields form an arc and the CA4 field has increased in size within the widened arch of the dentate gyrus.


The following data is from a postnatal magnetic resonance imaging study.[12]

  • 3 months - a longitudinal fasciculus of high signal intensity was seen in the white matter beneath the subiculum
  • birth to 2 years - volume increases rapidly
  • after 2 years - volume increases slowly thereafter
  • hippocampal formations on the right side were larger than those on the left in 38 cases (91%)
  • anterior temporal lobes on the right were larger than those on the left in 32 cases (76%)
  • right-left asymmetry of the hippocampal formations and anterior temporal lobes was observed from early infancy


The following data is from an magnetic resonance imaging study of adult Chinese aged 6 to 82 years.[13] Other studies have described a reduction in the hippocampal volume during ageing.

  • volume of right hippocampus was larger than that of the left side (p<0.001)
  • right side volume of hippocampus - 2.204 to 2.944 cm3
  • left side volume of hippocampus - 2.068 to 2.700 cm3
  • no statistically significant differences among different age and gender groups (p>0.05)

Adult hippocampal neurogenesis is influenced by both external stimuli and internal growth factors (BDNF, VEGF and IGF-1).[14]

Neuronal Development

The following data is from a histological study of postmortem hippocampi neurons.[15]

  • Bilateral coronal sections from postmortem hippocampus, 24 to 76 weeks postmenstrual age (gestational age plus postnatal age), were studied.
  • Cell body (soma) size correlated positively and significantly with age in CA2 and CA3, bilaterally.
  • CA2 somata were significantly larger (left, 34%; right, 32%) than adjacent CA3 somata.
  • Variability in soma form or size increased appreciably with age, in both subfields, bilaterally
  • Variability in soma orientation was weakly correlated with brain growth.

Mouse Hippocampus

Timeline comparison of the migration and layer arrangement in neocortex and hippocampal CA1 during cortical development[16]
Mouse cortex and hippocampus development (A) Neocortical neurons born between E10 and E12 radially migrate using the somal translocation mode. In contrast, late-born neurons transform their migration mode sequentially to multipolar migration, locomotion mode, and terminal translocation mode during their radial migration. These neurons form neocortical layers in a birthdate-dependent inside-out manner.

(B) Hippocampal CA1 neurons born at late developmental stages change the migration mode to multipolar migration and then to the climbing mode. The migration mode used by early-born CA1 neurons remains unknown (somal translocation mode is a candidate). The layer arrangement in the Ammon's horn is thought to occur roughly in a birth-date dependent inside-out manner.

PP, preplate; VZ, ventricular zone; MZ, marginal zone; CP, cortical plate; IZ, intermediated zone; MAZ, multipolar cell accumulation zone; WM, white matter; HP, hippocampal plate; SLM, stratum lacunosum-moleculare; SR, stratum radiatum; SP, stratum pyramidale; SO, stratum oriens.

(text modified from original figure legend)

Mouse- hippocampus dentate granule cells.jpg

The developmental changes of GFP+ newborn mouse dentate granule cells.[17]

Brain histology 02.jpg


  1. Caronia-Brown G, Yoshida M, Gulden F, Assimacopoulos S & Grove EA. (2014). The cortical hem regulates the size and patterning of neocortex. Development , 141, 2855-65. PMID: 24948604 DOI.
  2. 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. (2018). Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature , 555, 377-381. PMID: 29513649 DOI.
  3. Feng S, Shi T, Qiu J, Yang H, Wu Y, Zhou W, Wang W & Wu H. (2017). Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment. FASEB J. , 31, 4347-4358. PMID: 28611114 DOI.
  4. Hevner RF. (2016). Evolution of the mammalian dentate gyrus. J. Comp. Neurol. , 524, 578-94. PMID: 26179319 DOI.
  5. Montiel JF, Vasistha NA, Garcia-Moreno F & Molnár Z. (2016). From sauropsids to mammals and back: New approaches to comparative cortical development. J. Comp. Neurol. , 524, 630-45. PMID: 26234252 DOI.
  6. Striedter GF. (2016). Evolution of the hippocampus in reptiles and birds. J. Comp. Neurol. , 524, 496-517. PMID: 25982694 DOI.
  7. Li D, Takeda N, Jain R, Manderfield LJ, Liu F, Li L, Anderson SA & Epstein JA. (2015). Hopx distinguishes hippocampal from lateral ventricle neural stem cells. Stem Cell Res , 15, 522-529. PMID: 26451648 DOI.
  8. Bekiari C, Giannakopoulou A, Siskos N, Grivas I, Tsingotjidou A, Michaloudi H & Papadopoulos GC. (2015). Neurogenesis in the septal and temporal part of the adult rat dentate gyrus. Hippocampus , 25, 511-23. PMID: 25394554 DOI.
  9. Zhang Z, Liu S, Lin X, Teng G, Yu T, Fang F & Zang F. (2011). Development of laminar organization of the fetal cerebrum at 3.0T and 7.0T: a postmortem MRI study. Neuroradiology , 53, 177-84. PMID: 20981415 DOI.
  10. Knoth R, Singec I, Ditter M, Pantazis G, Capetian P, Meyer RP, Horvat V, Volk B & Kempermann G. (2010). Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS ONE , 5, e8809. PMID: 20126454 DOI.
  11. Kier EL, Kim JH, Fulbright RK & Bronen RA. (1997). Embryology of the human fetal hippocampus: MR imaging, anatomy, and histology. AJNR Am J Neuroradiol , 18, 525-32. PMID: 9090416
  12. Utsunomiya H, Takano K, Okazaki M & Mitsudome A. (1999). Development of the temporal lobe in infants and children: analysis by MR-based volumetry. AJNR Am J Neuroradiol , 20, 717-23. PMID: 10319988
  13. Li YJ, Ga SN, Huo Y, Li SY & Gao XG. (2007). Characteristics of hippocampal volumes in healthy Chinese from MRI. Neurol. Res. , 29, 803-6. PMID: 17601367 DOI.
  14. Lee E & Son H. (2009). Adult hippocampal neurogenesis and related neurotrophic factors. BMB Rep , 42, 239-44. PMID: 19470236
  15. Zaidel DW. (1999). Quantitative morphology of human hippocampus early neuron development. Anat. Rec. , 254, 87-91. PMID: 9892421
  16. Hayashi K, Kubo K, Kitazawa A & Nakajima K. (2015). Cellular dynamics of neuronal migration in the hippocampus. Front Neurosci , 9, 135. PMID: 25964735 DOI.
  17. Zhao S, Zhou Y, Gross J, Miao P, Qiu L, Wang D, Chen Q & Feng G. (2010). Fluorescent labeling of newborn dentate granule cells in GAD67-GFP transgenic mice: a genetic tool for the study of adult neurogenesis. PLoS ONE , 5, . PMID: 20824075 DOI.


Hippocampus - "source for investigators seeking the latest research on the hippocampal formation and related structures and is widely read by neuroscientists, anatomists, behavioral scientists, physiologists, biochemists, and cellular, developmental, and molecular biologists." Wiley[jour]


Gilchrist C, Cumberland A, Walker D & Tolcos M. (2018). Intrauterine growth restriction and development of the hippocampus: implications for learning and memory in children and adolescents. Lancet Child Adolesc Health , 2, 755-764. PMID: 30236384 DOI.

Salazar P, Cisternas P, Martinez M & Inestrosa NC. (2018). Hypothyroidism and Cognitive Disorders during Development and Adulthood: Implications in the Central Nervous System. Mol. Neurobiol. , , . PMID: 30073507 DOI.

Zeid D, Kutlu MG & Gould TJ. (2018). Differential Effects of Nicotine Exposure on the Hippocampus Across Lifespan. Curr Neuropharmacol , 16, 388-402. PMID: 28714396 DOI.

Greene ND & Copp AJ. (2009). Development of the vertebrate central nervous system: formation of the neural tube. Prenat. Diagn. , 29, 303-11. PMID: 19206138 DOI.

Li Y, Mu Y & Gage FH. (2009). Development of neural circuits in the adult hippocampus. Curr. Top. Dev. Biol. , 87, 149-74. PMID: 19427519 DOI.

Georgieff MK. (2008). The role of iron in neurodevelopment: fetal iron deficiency and the developing hippocampus. Biochem. Soc. Trans. , 36, 1267-71. PMID: 19021538 DOI.

Faulkner RL, Low LK & Cheng HJ. (2007). Axon pruning in the developing vertebrate hippocampus. Dev. Neurosci. , 29, 6-13. PMID: 17148945 DOI.

Parnavelas JG. (2000). The origin and migration of cortical neurones: new vistas. Trends Neurosci. , 23, 126-31. PMID: 10675917

Sitoh YY & Tien RD. (1997). The limbic system. An overview of the anatomy and its development. Neuroimaging Clin. N. Am. , 7, 1-10. PMID: 9100228


Bachevalier J. (2019). Nonhuman primate models of hippocampal development and dysfunction. Proc. Natl. Acad. Sci. U.S.A. , , . PMID: 31871159 DOI.

Anstey KJ, Maller JJ, Meslin C, Christensen H, Jorm AF, Wen W & Sachdev P. (2004). Hippocampal and amygdalar volumes in relation to handedness in adults aged 60-64. Neuroreport , 15, 2825-9. PMID: 15597062

Jack CR, Twomey CK, Zinsmeister AR, Sharbrough FW, Petersen RC & Cascino GD. (1989). Anterior temporal lobes and hippocampal formations: normative volumetric measurements from MR images in young adults. Radiology , 172, 549-54. PMID: 2748838 DOI.

Bhatia S, Bookheimer SY, Gaillard WD & Theodore WH. (1993). Measurement of whole temporal lobe and hippocampus for MR volumetry: normative data. Neurology , 43, 2006-10. PMID: 8413958

Search PubMed

Search Pubmed: Hippocampus Embryology | Hippocampus Development | Limbic Development

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2024, June 20) Embryology Neural - Hippocampus Development. Retrieved from

What Links Here?
© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G