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Event: 757
Key Event Title
Hippocampal anatomy, Altered
Short name
Biological Context
Level of Biological Organization |
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Tissue |
Organ term
Organ term |
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brain |
Key Event Components
Process | Object | Action |
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brain development | hippocampal formation | morphological change |
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
TPO Inhibition and Altered Neurodevelopment | KeyEvent | Kevin Crofton (send email) | Open for citation & comment | WPHA/WNT Endorsed |
Nuclear receptor induced TH Catabolism and Developmental Hearing Loss | KeyEvent | Katie Paul Friedman (send email) | Open for adoption | Under Development |
NIS and Cognitive Dysfunction | KeyEvent | Mary Gilbert (send email) | Under Development: Contributions and Comments Welcome | |
Transthyretin interference | KeyEvent | Kristie Sullivan (send email) | Under Development: Contributions and Comments Welcome | Under Development |
TR Antagonism and DNT | KeyEvent | Kevin Crofton (send email) | Under development: Not open for comment. Do not cite | Under Development |
Binding to voltage gate sodium channels during development leads to cognitive impairment | KeyEvent | Iris Mangas (send email) | Under development: Not open for comment. Do not cite | Under Review |
Taxonomic Applicability
Life Stages
Life stage | Evidence |
---|---|
During brain development | High |
Sex Applicability
Term | Evidence |
---|---|
Male | High |
Female | High |
Key Event Description
The hippocampus is a brain region located in the medial temporal lobe in humans and other mammals (West, 1990). Developmentally it is derived from neuronal and glial cells in the neural tube and differentiates in the proencephalon and telencephalon. The hippocampus is a cortical structure, but only contains 3-layers, distinct from the 6-layered neocortical structures. For this reason, it is known as archicortex or paleocortex meaning old cortex. In humans, at the macro level, the structure is identified as early as fetal week 13 and continues to mature until 2 to 3 years of age (Kier et al., 1997), with continuing slow growth thereafter until adult ages (Utsunomiya et al., 1999). In rodents, the hippocampus begins to form in mid-gestation, with the CA fields forming in advance of the dentate gyrus (Altman and Bayer, 1990a; 1990b). The primary structural and functional development of the hippocampus occurs in the third trimester of pregnancy in humans, whereas in rodents, much of the maturation of the CA fields and almost all dentate gyrus occurs in the first 2-3 postnatal weeks.
The structure of the hippocampus has been divided into regions that include CA1 through CA4 and the dentate gyrus. The principal cell bodies of the CA field are pyramidal neurons, those of the dentate gyrus are granule cells.
The major input pathway to the hippocampus is from the layer 2 neurons of the entorhinal cortex to the dentate gyrus via the perforant path forming the first connection of the trisynaptic loop of the hippocampal circuit (Figure 2). Direct afferents from the dentate gyrus (mossy fibers) then synapse on CA3 pyramidal cells which in turn send their axons (Schaeffer Collaterals) to CA1 neurons to complete the trisynaptic circuit. Information from the CA fields then passes through the subiculum entering the fiber pathways of the alveus, fimbria, and fornix and is routed to other areas of the brain (Amaral and Lavenex, 2006). Through the interconnectivity within the hippocampus and its connections to amygdala, septum and cortex, the hippocampus plays a pivotal role in several learning and memory processes, including spatial behaviors. The primary input pathway to the CA regions of the hippocampus is from the septum by way of the fornix and direct input from the amygdala. Reciprocal outputs from the hippocampus back to these regions and beyond also exist.
Figure 2. Trisynaptic circuit of hippocampal formation. For further details see Amaral and Lavenex, 2006.
At the cellular level, the components of the mammalian hippocampus undergo typical stages of neurodevelopment. With each developmental time window, distinct patterns of gene transcription and protein expression appear, corresponding to cell proliferation, differentiation, migration, synapse formation, and terminal neuronal/glial maturation, culminating in the structural formation of a neuronal network (Mody et al., 2001; Laeremans et al., 2013). The principal neurons of the CA fields develop in advance of the principal cells of the dentate gyrus and the genes and proteins controlling the distinct phases are expressed at different stages in these two sub-regions (Altman and Bayer, 1990 a, b; Laeremans et al., 2013). In the rodent brain, almost all neurons show extensive growth and differentiation on axons and dendrites during the first postnatal week. These cellular changes are marked by rapid protein expression specific for different neuronal and glial subtypes including cytoskeletal proteins (e.g. cofilin, actins, tubulins etc..), production of cell adhesion molecules, and extracellular matrix formation which are critical structural elements of a neuronal network.
As neurons mature, they extend dendritic processes that lengthen and branch, the ends of which broaden to form a spine head. Dendritic spines form the postsynaptic structural component of most excitatory synapses in the mammalian brain, including hippocampus. The spine head has a greater potential for connectivity and synapse formation (Dailey and Smith, 1996; Fiala et al., 1998; Hardy, LR and Redmond, 2008, Pfeiffer et al., 2018). The postsynaptic density-95 (PSD-95) is one of the key proteins involved in dendritic spine maturation, clustering of synaptic signalling proteins, and ultimately mediating synaptic transmission. It also plays a critical role in regulating dendrite outgrowth and branching and formation dendritic spines.
As the hippocampus matures during the postnatal period hippocampal circuits become more active and exhibit increased activity-dependent plasticity. Many genes and proteins are upregulated during this phase of development, especially molecules involved in the axon guidance (e.g. BDNF/CREB) (Hinkemeyer et al., 2003; Shen and Cowan., 2010), dendritic spine formation (e.g. Neuroligin, Ephrins) and synaptogenesis. Increased expression of vesicle associated proteins (e.g., SNAP-25), synaptic vesicle proteins (e.g., synaptophysin, synapsin I) and proteins involved in sodium and calcium-mediated transmitter release occurs during this period. These changes are accompanied by a parallel increase in neurotrophins and neurotransmitters, receptors and ion channels (Sudhof, 2018; Zhong et al., 2020; Rizo and Rosenmund, 2008). Therefore, any alterations in the expression of these proteins (Figure 3) may result in changes of synapse formation, followed by alteration of neuronal networks within the hippocampus.
Figure 3. The main structural components of the synapse: (A) a presynaptic and a postsynaptic neuron, separated by a synaptic cleft; (B) the dendritic spines and (C) the proteins involved in synaptic formation and transmission, including synaptic vesicle (SV), presynaptic and postsynaptic proteins present in excitatory and inhibitory synapse. Adapted from Serrano et al., 2022.
The dendritic spine represents the primary site of synaptic activity at the postsynaptic site. A variety of proteins present in the presynaptic terminal and the postsynaptic dendritic spine are expressed at different times during synaptogenesis, perturbation of which can negatively impact synaptic formation and structure at the macro- and ultra- structural level.
The use of genetically modified mouse models has been widely applied to delineate a host of different proteins involved in the structural development of the hippocampus (Joo et al., 2020). With this approach, changes in neuronal morphology, synapse and network formation in the hippocampus are contrasted in animals lacking this protein vs ‘wild type’ mice where the protein has been maintained. These comparisons have adopted a variety of techniques, several described below. In KE4, differential expression of proteins identified in these model systems is taken as evidence of altered structure.
However, it is essential to consider the timing of events during development, when their detection is optimal (Hevner, 2007; Garman et al., 2001; Zgraggen et al., 2012). Some macrolevel structural changes may be transient yet still significantly impact downstream events. In the case of knockout models, it is also important to recognize that in most cases, the protein has been removed for the entire lifespan of the animal, in the brain and elsewhere in the body, a scenario distinct from a chemical perturbation.
How It Is Measured or Detected
Data in support of this key event have been collected using a wide variety of standard biochemical, molecular, cellular, histological and anatomical methods (e.g., morphometrics, protein quantification using different types of cellular staining, immunohistochemistry, and imaging procedures) at different stages of hippocampus development. Many of methods applied are routine neurohistopathology procedures like those recommended in EPA and OECD developmental neurotoxicity guidelines (US EPA, 1998; OCED, 2007). The quantification of cell body and neurite proteins can be carried out by performing immunocytochemistry and automated high content imaging analyses in in vitro and in vivo preparations (Harrill and Mundy, 2011, Meng et al., 2002), Pistollato et al., 2020). Subtle cytoarchitectural features depend on more specialized birth dating procedures and staining techniques. At the micro- and ultra- structural levels, changes in neuronal and glial morphology, alterations in synapse structure, dendritic spine formation (size, shape, number, distribution of head/neck ratios in hippocampal cultures or in vivo studies) and dendritic morphology (branching points, length etc..) can be assessed in Golgi-Cox impregnated neurons (Bongmbaa et al., 2011), two-photon microscopy (Ehrlich et al., 2007), transmission electron (TEM) and fluorescent microscopy ( Runge et al., 2020; Pchitskaya et al., 2020)
Two-photon time-lapse images can be used to visualise dendrites in GFP-transfected neurons, whereas Golgi Stain is used to measure both dendrites and dendritic spines. A combination of Golgi-Cox and immunofluorescence using confocal microscopy has also been suggested for the visualisation of dendrites in brain slices derived either from rodents or non-human primates (Levine et al., 2013).
Fluorescent markers, such as Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) permits not only the visualisation of detailed dendritic arborizations and spines in cell culture and tissue sections but is also compatible with the quantitative analysis of dendritic spine number (Cheng et al., 2014).
Immunostaining with specific antibodies that recognize presynaptic proteins of excitatory and inhibitory neurons (i.e., vesicular glutamate transporters, vesicular GABA proteins and transporters) and the postsynaptic density protein-95 kDa (PSD-95) can be applied to enumerate synapse number (Gatto and Broadie, 2010, Akashi et al., 2009). There are commercially available ‘synaptogenesis assay kits’ that rely on the immunostaining of cells with common synaptic marker proteins such as MAP-2, PSD-95 and synaptophysin. Some other presynaptic (Bassoon) and postsynaptic (ProSAP1/Shank2) markers have been shown to correlate well with the ultrastructural studies in cultured hippocampus primary cells (Grabrucker et al., 2009).
Electron microscopy can also be applied to assess the prevalence of excitatory and inhibitory synapses amongst convergent contacts (Megias et al., 2001). Recently, a high content image analysis based on RNAi screening protocols has been suggested as a useful tool to create imaging algorithm for use in both in vitro and in vivo synaptic punctae analysis (Nieland et al., 2014).
Some of the same techniques used in rodent studies have been applied to postmortem tissue in humans. In addition, non-invasive, structural neuroimaging techniques in living subjects are also widely used in human studies to assess hippocampal volume using voxel-based morphometry (VBM). With this approach, volume of brain regions is measured by drawing ‘regions of interest’ on images from brain scans obtained from magnetic resonance imaging (MRI) or positron emission tomography (PET) scans calculating the volume enclosed (Mechelli et al., 2005). These imaging techniques can be applied in rodent models (Powell et al., 2009; Hasegawa et al., 2010; Pirko et al., 2005; Pirko and Johnson, 2008).
It is recognized that most of these biochemical, molecular, cellular, histological and anatomical methods (e.g., morphometrics, protein quantification using different types of cellular staining, immunohistochemistry, and imaging procedures) can also be applied to complex in vitro test systems (Pamies et al., 2016; Hartman et al., 2023; Pomeshchik et al., 2020) Human brain spheres or brain organoids could be developed in three-dimensional cell culture, resembling hippocampus at different stages development (Sakaguchi et al., 2015). These new methods, if assessed as robust, reliable and reproducible, would allow measurement of the KE in a human-relevant test system.
Domain of Applicability
The hippocampus is generally similar in structure function across most mammalian species (West, 1990). The vast majority of information on the structure of the hippocampus is from mice, rats and primates including humans.
References
Akashi K, Kakizaki T, Kamiya H, Fukaya M, Yamasaki M, Abe M, Natsume R, Watanabe M, and Sakimura K,2009.NMDA Receptor GluN2B (GluR 2/NR2B) Subunit Is Crucial for Channel Function, Postsynaptic Macromolecular Organization, and Actin Cytoskeleton at Hippocampal CA3 Synapses. The Journal of Neuroscience, 29(35):10869 –10882.
Altman J and Bayer SA, 1990b. Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale. The Journal of comparative neurology, 301(3), 343–364. https://doi.org/10.1002/cne.903010303
Altman J and Bayer SA,1990a. Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. The Journal of comparative neurology, 301(3), 365–381. https://doi.org/10.1002/cne.903010304
Amaral D and Lavenex P ,2006. "Chapter 3. Hippocampal Neuroanatomy". In: Andersen P, Morris R, Amaral D, Bliss T, O'Keefe J. The Hippocampus Book. Oxford University Press. ISBN 978-0-19-510027-3.
Bongmbaa OYN, Martineza L.A, Elhardta ME, Butlera K, and Tejada-Simona MV, 2011, Modulation of dendritic spines and synaptic function by Rac1: a possible link to Fragile X syndrome pathology. Brain research, 1399, 79–95. https://doi.org/10.1016/j.brainres.2011.05.020
Cheng C, Trzcinski O and Doering LC,2014. Fluorescent labeling of dendritic spines in cell cultures with the carbocyanine dye "DiI". Frontiers in neuroanatomy, 8, 30. https://doi.org/10.3389/fnana.2014.00030
Dailey ME, and Smith SJ, 1996. The Dynamics of Dendritic Structure in Developing Hippocampal Slices. Journal of Neuroscience, 16 (9) 2983-2994.https://doi.org/10.1523/JNEUROSCI.16-09-02983.1996
Ehrlich I, Klein M, Rumpel S, and Malinow R,2007. PSD-95 is required for activity-driven synapse stabilization. PNAS, 104; 4181. 104 (10) 4176-4181.https://doi.org/10.1073/pnas.0609307104
Fiala JC, Feinberg M, Popov V, Harris KM. 1998. Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. The Journal of neuroscience : the official journal of the Society for Neuroscience, 18(21), 8900–8911. https://doi.org/10.1523/JNEUROSCI.18-21-08900.1998
Garman RH, Fix AS, Jortner BS, Jensen KF, Hardisty JF, Claudio L, Ferenc S. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology. Environ Health Perspect. 2001 Mar;109 Suppl 1:93-100.
Gatto CL, Broadie K. (2010) Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models. Front Syn Neurosci. 2: 4.
Grabrucker A, Vaida B, Bockmann J, Boeckers TM. (2009) Synaptogenesis of hippocampal neurons in primary cell culture. Cell Tissue Res. 338: 333-341.
Hardy, LR & Redmond, L 2008, 'Translating neuronal activity into dendrite elaboration: Signaling to the nucleus', NeuroSignals, vol. 16. Doi: 10.1159/000111563
Hardy, LR & Redmond, L 2008, 'Translating neuronal activity into dendrite elaboration: Signaling to the nucleus', NeuroSignals, vol. 16.
Harrill JA, Mundy WR, 2011, Quantitative assessment of neurite outgrowth in PC12 cells. Methods Mol Biol., 758:331-48. doi: 10.1007/978-1-61779-170-3_23.
Hartmann J, Henschel N, Bartmann K, Dönmez A, Brockerhoff G, Koch K, Fritsche E. Molecular and Functional Characterization of Different BrainSphere Models for Use in Neurotoxicity Testing on Microelectrode Arrays. Cells. 2023 Apr 27;12(9):1270. doi: 10.3390/cells12091270.
Hasegawa M, Kida I, Wada H. A volumetric analysis of the brain and hippocampus of rats rendered perinatal hypothyroid. Neurosci Lett. 2010 Aug 2;479(3):240-4.
Hevner RF. Layer-specific markers as probes for neuron type identity in human neocortex and malformations of cortical development. J Neuropathol Exp Neurol. 2007 66(2):101-9.
Hinkemeyer M, Itkis OS, Ngo M, Hickmott PW, Ethell IM 2003. Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol 2003, 163:1313–1326. Front Mol Neurosci.
Joo, Y., Xue, Y., Wang, Y. et al. Topoisomerase 3β knockout mice show transcriptional and behavioural impairments associated with neurogenesis and synaptic plasticity. Nat Commun 11, 3143 (2020). https://doi.org/10.1038/s41467-020-16884-4
Kier, EL, Kim, JH, Fulbright, K, Bronen, RA. Embryology of the human fetal hippocampus: MR imaging, anatomy, and histology. AJNR Am J Neuroradiol: 1997, 18(3);525-32.
Laeremans, A, Van de Plas, B, Clerens, S, Van den Bergh, G, Arckens, L, Hu. TT. Protein Expression Dynamics During Postnatal Mouse Brain Development. J Exp Neurosci. 2013; 7: 61–74).
Levine ND, Rademacher DJ, Collier TJ, O'Malley JA, Kells AP, San Sebastian W, Bankiewicz KS, Steece-Collier K. (2013) Advances in thin tissue Golgi-Cox impregnation: fast, reliable methods for multi-assay analyses in rodent and non-human primate brain. J Neurosci Methods 213: 214-227.
Mechelli A, Price C, Friston K, Ashburner J (2005) Voxel-Based Morphometry of the Human Brain: Methods and Applications. Curr Med Imaging Rev 1:105-113.
Megias M, Emri Z, Freund TF, Gulyas AI. (2001) Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells. Neuroscience 102: 527-540.
Meng Y, Zhang Y, Tregoubov V, Janus C, Cruz L, Jackson M, Lu WY, MacDonald JF, Wang JY, Falls DL, Jia Z.,2002, Abnormal Spine Morphology and Enhanced LTP in LIMK-1 Knockout Mice. Neuron, 35;121–133.
Mody M, Cao Y, Cui Z, Tay KY, Shyong A, Shimizu E, Pham K, Schultz P, Welsh D, Tsien JZ. Genome-wide gene expression profiles of the developing mouse hippocampus. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8862-7.
Nieland TJF, Logan DJ, Saulnier J, Lam D, Johnson C, et al. (2014) High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons. PLoS ONE. 9: e91744.
Odawara A, Katoh H, Matsuda N, Suzuki I. Induction of long-term potentiation and depression phenomena in human induced pluripotent stem cell-derived cortical neurons. Biochem Biophys Res Commun. 2016 Jan 22;469(4):856-62. doi: 10.1016/j.bbrc.2015.12.087.
OECD Initial Recommendations on Evaluation of Data from the Developmental Neurotoxicity (DNT) In-Vitro Testing Battery; Series on Testing and Assessment No. 377. 2023. Available at: https://one.oecd.org/document/ENV/CBC/MONO(2023)13/en/pdf
OECD. 2007. OECD guidelines for the testing of chemicals/ section 4: Health effects. Test no. 426: Developmental neurotoxicity study. http://www.oecd.org/dataoecd/20/52/37622194.
Pamies D, Barreras P, Block K, Makri G, Kumar A, Wiersma D, Smirnova L, Zang C, Bressler J, Christian KM, Harris G, Ming GL, Berlinicke CJ, Kyro K, Song H, Pardo CA, Hartung T, Hogberg HT. A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity. ALTEX. 2017;34(3):362-376. doi: 10.14573/altex.1609122. Epub 2016 Nov 24. PMID: 27883356; PMCID: PMC6047513.
Pchitskaya E, and Bezprozvanny I, 2020, Dendritic Spines Shape Analysis—Classification or Clusterization? Perspective. Front. Synaptic Neurosci., Front Synaptic Neurosci., 30;12:31.
Pfeiffer T, Poll S, Bancelin S, Angibaud J, Inavalli K, Keppler K, Mittag M, Fuhrmann M, Nägerl V., (2018) Chronic 2P-STED imaging reveals high turnover of dendritic spines in the hippocampus in vivo. eLife, 7, e34700. https://doi.org/10.7554/eLife.34700
Pirko I and Johnson AJ,2008. Neuroimaging of demyelination and remyelination models. Current topics in microbiology and immunology, 318, 241–266. https://doi.org/10.1007/978-3-540-73677-6_10
Pirko I, Fricke ST, Johnson AJ, Rodriguez M and Macura SI,2005. Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics, 2(2), 250–264. https://doi.org/10.1602/neurorx.2.2.250
Pistollato F, de Gyves EM, Carpi D, Bopp SK, Nunes C, Worth A, Bal-Price A. Assessment of developmental neurotoxicity induced by chemical mixtures using an adverse outcome pathway concept. Environmental health : a global access science source, 19(1), 23. https://doi.org/10.1186/s12940-020-00578-x
Pomeshchik Y, Klementieva O, Gil J, Martinsson I, Hansen MG, de Vries T, Sancho-Balsells A, Russ K, Savchenko E, Collin A, Vaz AR, Bagnoli S, Nacmias B, Rampon C, Sorbi S, Brites D, Marko-Varga G, Kokaia Z, Rezeli M, Gouras GK, Roybon L. Human iPSC-Derived Hippocampal Spheroids: An Innovative Tool for Stratifying Alzheimer Disease Patient-Specific Cellular Phenotypes and Developing Therapies. Stem Cell Reports. 2020 Jul 14;15(1):256-273. doi: 10.1016/j.stemcr.2020.06.001. Epub 2020 Jun 25. Erratum in: Stem Cell Reports. 2021 Nov 9;16(11):2838. Erratum in: Stem Cell Reports. 2023 May 9;18(5):1244-1245.
Powell MH, Nguyen HV, Gilbert M, Parekh M, Colon-Perez LM, Mareci TH and Montie E,2012. Magnetic resonance imaging and volumetric analysis: novel tools to study the effects of thyroid hormone disruption on white matter development. Neurotoxicology, 33(5), 1322–1329. https://doi.org/10.1016/j.neuro.2012.08.008
Pré D, Wooten AT, Biesmans S, Hinckley S, Zhou H, Sherman SP, Kakad P, Gearhart J, Bang AG. Development of a platform to investigate long-term potentiation in human iPSC-derived neuronal networks. Stem Cell Reports. 2022 Sep 13;17(9):2141-2155. doi: 10.1016/j.stemcr.2022.07.012.
Rizo J and Rosenmund CH,2008. Synaptic vesicle fusion. Nature structural & molecular biology, 15(7), 665–674. https://doi.org/10.1038/nsmb.1450 .
Runge K, Cardoso C and de Chevigny A,2020. Dendritic Spine Plasticity: Function and Mechanisms. Frontiers in synaptic neuroscience, 12, 36. https://doi.org/10.3389/fnsyn.2020.00036
Sakaguchi, H., Kadoshima, T., Soen, M. et al. Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue. Nat Commun 6, 8896 (2015). https://doi.org/10.1038/ncomms9896
Serrano M. E., Kim E, Petrinovic M.M, Turkheimer F and Cash D. 2022.Imaging Synaptic Density: The Next Holy Grail of Neuroscience? Frontiers in Neuroscience, Volume 16 - 2022 https://doi.org/10.3389/fnins.2022.796129
Shen K. and Cowan CW,2010. Guidance molecules in synapse formation and plasticity. Cold Spring Harbor perspectives in biology, 2(4), a001842. https://doi.org/10.1101/cshperspect.a001842
Sudhof TC,2018. Towards an Understanding of Synapse Formation. Neuron, 100(2), 276–293. https://doi.org/10.1016/j.neuron.2018.09.040
U.S.EPA. 1998. Health effects guidelines OPPTS 870.6300 developmental neurotoxicity study. EPA Document 712-C-98-239.Office of Prevention Pesticides and Toxic Substances.
Utsunomiya H, Takano k, Okazaki M and Mitsudome A,1999. Development of the temporal lobe in infants and children: analysis by MR-based volumetry. AJNR. American journal of neuroradiology, 20(4), 717–723.
West MJ ,1990. "Chapter 2 : Stereological studies of the hippocampus: a comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men". In:Progress in Brain Research. Progress in Brain Research ,83: 13–36.
Zgraggen E, Boitard M, Roman I, Kanemitsu M, Potter G, Salmon P, Vutskits L, Dayer AG, Kiss JZ,2012. Early Postnatal Migration and Development of Layer II Pyramidal Neurons in the Rodent Cingulate/Retrosplenial Cortex, Cerebral Cortex, 22(1), 144–157. https://doi.org/10.1093/cercor/bhr097
Zhong S, Ding W, Sun L, Lu Y, Dong H, Fan X, Liu Z, Chen R, Zhang S, Ma Q, Tang F, Wu Q and Wang X,2020. Decoding the development of the human hippocampus. Nature ,577, 531–536.https://doi.org/10.1038/s41586-019-1917-5