FIGURE 3 - uploaded by Shihhui Huang
Content may be subject to copyright.
| Principal hippocampal subdivisions in the marmoset. (A) Major hippocampal subdivisions in Giemsa-stained marmoset mid-septotemporal hippocampus. Arrows mark the boundaries between subdivisions at the level of the cell layer(s). (B) Definitions of the principal cell population in the marmoset mid-septotemporal hippocampus. (C) Complex hilar cytoarchitecture of the marmoset dentate gyrus that is common in non-rodent species. (D) Definitions of the regions that have been used to define CA3 and hilar cell populations within the dentate gyrus; 1: CA3 or CA3o (outer CA3, Houser et al., 1990), 2: reflected blade of CA3 (Lorente De Nó, 1934) or CA3h (used in this study; Lim et al., 1997; Ding and Van Hoesen, 2015) or CA3i (inner CA3, Houser et al., 1990) or CA4 (Rosene and Van Hoesen, 1987), 3: polymorphic cell layer (2+3: CA4 of Lorente De Nó, 1934), and 4: plexiform layer (Cajal, 1968), 5: dentate granule cells. Stratum radiatum (6) and stratum oriens (7) insert themselves superficial and deep to CA3h. The separation between CA3h and the hilar polymorphic layer is variable in different species and at different septotemporal levels. When the CA3h and the polymorphic cell layer merge, we cannot reliably distinguish CA3h cells from hilar polymorphic cells in Nissl-stained preparations. Scale bars: 250 µm.
Source publication
While many differences in hippocampal anatomy have been described between species, it is typically not clear if they are specific to a particular species and related to functional requirements or if they are shared by species of larger taxonomic units. Without such information, it is difficult to infer how anatomical differences may impact on hippo...
Contexts in source publication
Context 1
... of the variable nomenclature of CA3 pyramidal cells close (proximal) to the dentate gyrus and recent revisions, this region and the borders that it contains is illustrated in Figure 3 for the marmoset monkey. Cytoarchitectural differentiation in marmoset monkeys largely corresponds to that seen in all non-rodent species included in this study. ...
Context 2
... four species, together with humans and dogs, also share a reflected blade of the CA3 pyramidal cell layer. In our study, as well as in all sources used in this study, these cells are included in the cell counts of the hilus (see Figure 3 and Discussion). Along the second axis, in addition to hilar and CA3 populations, further distinction is made by the subiculum and CA1 (26% and 19%, respectively), which results in a separation of the human hippocampus, marked by both a large CA1 and small (Cajal, 1968), 5: dentate granule cells. ...
Context 3
... reflected blade of CA3 has also been named CA3h ( Lim et al., 1997;Ding and Van Hoesen, 2015), avoiding the ambiguity associated with the heterogeneously defined alternative term CA4 (e.g., Lorente De Nó, 1934;Rosene and Van Hoesen, 1987). In all the sources that we have used and in the non-rodent species that we assessed ourselves, CA3h cells have been included in the estimates of hilar cell numbers ( Figure 3D, number 2 and 3). In our case and most likely in the sources as well, this decision was made because a reliable border between CA3h and the remainder of CA3 is far easier to define than the border between CA3h and the hilar polymorphic cell layer that contains the bulk of the "proper" hilar cells. ...
Similar publications
Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while produc...
Citations
... Studies evaluating the lifespan production of new neurons have shown more moderate figures. (Ninkovic et al., 2007;Imayoshi et al., 2008) used transgenic mice to label newly generated cells and reported values between 8-10% of the total population of 500,000 GCs (Kempermann et al., 1997a;Calhoun et al., 1998;Ben Abdallah et al., 2010;van Dijk et al., 2016), representing 40-50,000 new neurons added along adulthood. (Pilz et al., 2018) studied the process of neurogenesis in vivo and estimated that radial glial progenitors will produce on average 4.5 neurons that combined with the approximately 10,000 radial glial cells present in a 2-month-old mouse described by (Encinas et al., 2011) would mean that about 45,000 new neurons (or 9% of the total) are generated along the adult life of mice. ...
... ; The modeled number of DCX labeled cells, DFNs and their percentages from the total population of GCs are shown in Table 1A and 1B for mice and rats respectively. Total population was estimated to be 500,000 GCs in the mouse (Kempermann et al., 1997a;Calhoun et al., 1998;Ben Abdallah et al., 2010;van Dijk et al., 2016) and about 1,000,000 GCs in the rat (Boss et al., 1985;West et al., 1991;Hosseini-Sharifabad and Nyengaard, 2007;Fitting et al., 2010); data per hemisphere). was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. ...
Contrary to humans, adult neurogenesis in rodents is not controversial. And in the last three decades, multiple studies in rodents have deemed adult neurogenesis essential for most hippocampal functions. The functional relevance of new neurons relies on their distinct physiological properties during their maturation before they become indistinguishable from mature granule cells. Most functional studies have used very young animals with robust neurogenesis. However, this trait declines dramatically with age, questioning its functional relevance in aging animals, a caveat that has been mentioned repeatedly, but rarely analyzed quantitatively. In this meta-analysis, we use data from published studies to determine the critical functional window of new neurons and to model their numbers across age in both mice and rats. Our model shows that new neurons with distinct functional profile represent about 3% of the total granule cells in young adult 3-month-old rodents, and their number decline following a power function to reach less than 1% in middle aged animals and less than 0.5% in old mice and rats. These low ratios pose an important logical and computational caveat to the proposed essential role of new neurons in the dentate gyrus, particularly in middle aged and old animals, a factor that needs to be adequately addressed when defining the relevance of adult neurogenesis in hippocampal function.
... Contrarily to GABAergic interneurons, glutamatergic principal cells comprise a majority of neurons in the hippocampus [46]. Also, in contrast to interneurons, principal cells display a distinct layered organizational pattern with a relatively high level of anatomical uniformity [83,84]. Nav1.6 is extensively expressed in the adult human brain and is the predominant Nav isoform in hippocampal principal cells [85]. ...
Alzheimer’s disease (AD) is the most common cause of dementia and is classically characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta (Aβ) and intracellular hyperphosphorylated tau. Due to the progressive nature of the disease, it is of the utmost importance to develop disease-modifying therapeutics that tackle AD pathology in its early stages. Attenuation of hippocampal hyperactivity, one of the earliest neuronal abnormalities observed in AD brains, has emerged as a promising strategy to ameliorate cognitive deficits and abate the spread of neurotoxic species. This aberrant hyperactivity has been attributed in part to the dysfunction of voltage-gated Na+ (Nav) channels, which are central mediators of neuronal excitability. Therefore, targeting Nav channels is a promising strategy for developing disease-modifying therapeutics that can correct aberrant neuronal phenotypes in early-stage AD. This review will explore the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets.
... When protected animal species or humans are involved, the post-mortem interval, as well as the type of fixation, cannot be the same as in laboratory rodents. Consequently, even when several animal species are considered in the same study and thus processed by using the same methods, the original conditions of the tissues cannot be exactly the same [23,79,80,81]. Conversely, when a single animal species is investigated to find the best conditions to ...
... When protected animal species or humans are involved, the post-mortem interval, as well as the type of fixation, cannot be the same as in laboratory rodents. Consequently, even when several animal species are considered in the same study and thus processed by using the same methods, the original conditions of the tissues cannot be exactly the same [23,[79][80][81]. Conversely, when a single animal species is investigated to find the best conditions to detect antigens in that brain tissue (a most frequent event in the literature), comparison with other species can be tricky. ...
... As a result, the gap between our knowledge in rodents and humans remains widely unexplored, hampering the identification of real phylogenetic variations that might be useful for the correct interpretation of data obtained in mice and for a proper translation [85,88]. Nonetheless, most comparative studies consider either a single animal species or a small group of them, while analysing different species with the same method/approach in a study is rare (e.g., [23,79,80]). Finally, in studies using immunocytochemical markers on post-mortem tissues, several antibodies raised against the same antigen are often reported in the Section 4 without stating which of them achieved successful staining or in which condition/treatment. ...
Recently, a population of “immature” neurons generated prenatally, retaining immaturity for long periods and finally integrating in adult circuits has been described in the cerebral cortex. Moreover, comparative studies revealed differences in occurrence/rate of different forms of neurogenic plasticity across mammals, the “immature” neurons prevailing in gyrencephalic species. To extend experimentation from laboratory mice to large-brained mammals, including humans, it is important to detect cell markers of neurogenic plasticity in brain tissues obtained from different procedures (e.g., post-mortem/intraoperative specimens vs. intracardiac perfusion). This variability overlaps with species-specific differences in antigen distribution or antibody species specificity, making it difficult for proper comparison. In this work, we detect the presence of doublecortin and Ki67 antigen, markers for neuronal immaturity and cell division, in six mammals characterized by widely different brain size. We tested seven commercial antibodies in four selected brain regions known to host immature neurons (paleocortex, neocortex) and newly born neurons (hippocampus, subventricular zone). In selected human brains, we confirmed the specificity of DCX antibody by performing co-staining with fluorescent probe for DCX mRNA. Our results indicate that, in spite of various types of fixations, most differences were due to the use of different antibodies and the existence of real interspecies variation.
... These values are much higher than the ones found in the present work for the human CA1 (Table 1). Such huge differences in synaptic density between humans and rodentstogether with the above-mentioned divergences in the morphology and distribution of pyramidal cells in the SP of CA1 (Benavides-Piccione et al., 2020), as well as differences in other anatomical, genetic, molecular and physiological features (Benavides-Piccione et al., 2020;Blazquez-Llorca et al., 2020;Ding, 2013;Hawrylycz et al., 2012;Santuy et al., 2020;Tapia-González et al., 2020;van Dijk et al., 2016)-further support the notion that there are remarkable differences between the human and rodent CA1. These differences clearly need to be taken into consideration when making interpretations in translational studies comparing one species to another. ...
The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed in CA1, revealing that most of them were excitatory, targeting dendritic spines and displaying a macular shape, regardless of the layer examined. However, remarkable differences were observed between layers. These data constitute the first extensive description of the synaptic organization of the neuropil of the human CA1 region.
... These values are much higher than the ones found in the present work for the human CA1 (Table 1). Such huge differences in synaptic density between humans and rodentstogether with the above-mentioned divergences in the morphology and distribution of pyramidal cells in the SP of CA1 (Benavides-Piccione et al., 2020), as well as differences in other anatomical, genetic, molecular and physiological features (Benavides-Piccione et al., 2020;Blazquez-Llorca et al., 2020;Ding, 2013;Hawrylycz et al., 2012;Santuy et al., 2020;Tapia-González et al., 2020;van Dijk et al., 2016)-further support the notion that there are remarkable differences between the human and rodent CA1. These differences clearly need to be taken into consideration when making interpretations in translational studies comparing one species to another. ...
The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed in CA1, revealing that most of them were excitatory, targeting dendritic spines and displaying a macular shape, regardless of the layer examined. However, remarkable differences were observed between layers. These data constitute the first extensive description of the synaptic organization of the neuropil of the human CA1 region.
... These values are much higher than the ones found in the present work for the human CA1 (Table 1). Such huge differences in synaptic density between humans and rodentstogether with the above-mentioned divergences in the morphology and distribution of pyramidal cells in the SP of CA1 (Benavides-Piccione et al., 2020), as well as differences in other anatomical, genetic, molecular and physiological features (Benavides-Piccione et al., 2020;Blazquez-Llorca et al., 2020;Ding, 2013;Hawrylycz et al., 2012;Santuy et al., 2020;Tapia-González et al., 2020;van Dijk et al., 2016)-further support the notion that there are remarkable differences between the human and rodent CA1. These differences clearly need to be taken into consideration when making interpretations in translational studies comparing one species to another. ...
The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed in CA1, revealing that most of them were excitatory, targeting dendritic spines and displaying a macular shape, regardless of the layer examined. However, remarkable differences were observed between layers. These data constitute the first extensive description of the synaptic organization of the neuropil of the human CA1 region.
... https://doi.org/10.1101/2020.02.25.964080 doi: bioRxiv preprint other anatomical, genetic, molecular and physiological features (18,(21)(22)(23)(24)(25)-further support the notion that there are remarkable differences between the human and rodent CA1. These differences clearly need to be taken into consideration when making interpretations in translational studies comparing one species to another. ...
The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed in CA1, revealing that most of them were excitatory, targeting dendritic spines and displaying a macular shape, regardless of the layer examined. However, remarkable differences were observed between layers. These data constitute the first extensive description of the synaptic organization of the neuropil of the human CA1 region.
... In 2016, van Dijk published a systematic review comparing the hippocampus in 18 different species, where one pig study was reported [4]. ...
... So far, only one paper was found to address this topic. [4] However, the use of open source software to stereologically study the hippocampus was not mentioned as part of the reported methodology. The use of open source software (in our case, ImageJ) is a novel and cheaper approach to stereologically analyze the brain tissue. ...
Most neuro-pathophysiological research involving the hippocampus uses rodents as a nonhuman model, due to the extensive experimental descriptive literature and favorable cost. The findings from the rodent hippocampus may not be generalizable to humans, though, as ontogenetically they have different hippocampal components. While the rodent model has these limitations, the use of nonhuman primates is often not feasible due to economic and ethical considerations. Pigs are a translational alternative due to the anatomic similarity of the hippocampus in humans and pigs. Materials and Methods: Eight pigs’ brains were harvested and then analyzed according to our previously established technique. Five brains were frozen and three were stored in formalin. All eight brains were then sent to an independent histology service, where they were sectioned according to the methodology established by Holm 1994. The slabs were 10 µm with 2.5 cm2 of hippocampus cross-sectional area. Results: The mean total hippocampus volume was 892.84 mm3 ± 198.91 mm3 using Holm’s methodology. The mean number of cells per sample (20X magnification settings) was 9996.75, using automated ImageJ cell counting. Discussion: In this study, the counts of hippocampus cells were divided into two regions of interest: CA1 and CA3. Our results show that the mean number of hippocampus cells observed was 5.75 million and 2.25 million, in the CA1 and CA3 regions respectively. Holm reported 4.12 million cells in the CA1 region and 1.51 million cells in the CA3 region. The results presented here indicate the CA1 and CA3 cell percentages being 23% and 9% respectively, which are similar to the percentages reported by Holm (21% and 12%). Conclusion: These results corroborate previous findings and demonstrate a novel and cost-effective way to study the hippocampus of pigs in translational neurological research.
... Several studies carried out during the last two decades on mammalian species different from mice and rats started to show that adult neurogenesis occurrence, extension, rate, behavioral role(s), and function(s) can be quite heterogeneous among mammals (reviewed in [10,17,81,85,87]). This heterogeneity can occur at three main levels: (i) Different anatomical location, consisting of differences in the existence/location/outcome of neurogenic sites among species (linked to neuroanatomy and specific brain functions; see above the example of striatum and cerebellum in rabbits, and, outside of mammals, the seasonal neurogenesis in the bird telecephalon [58]; (ii) different rate among species, consisting of differences detectable in the same neurogenic region (e.g., the hippocampus of different species of bats or rodents [81,88]); (iii) different rate among ages within the same species (characterized by a general reduction after puberty and then further reduction with aging, but with remarkable interspecies differences linked to the different postnatal developmental/growth time scales [89][90][91]). In other words, the issue of adult neurogenesis reduction in mammals is made even more complex by the superposition of a "phylogenetic" decline (emerging when comparing different animal species) with a decline "linked to progressive ages" detectable in individuals of the same species (and usually present in all species). ...
... No systematic, fully comparable studies (e.g., involving the count of dividing and DCX+ cells in different animal species, at corresponding ages, and in relation to the count of the different cell populations residing in the hippocampus, primarily granule cells) are available on a wide range of mammalian species to support this view or evaluate the importance of conservation in adult neurogenesis. An existent analysis, mostly based on rodent species, indicates that the rate of the neurogenesis varies widely, even between closely related members of the order Rodentia [88]. We know more about the "extremes": High neurogenic rates in laboratory rodents (small-brained, lissencephalic) and vestigial/absent neurogenesis in humans and dolphins (large-brained, highly gyrencephalic). ...
Brain plasticity is important for translational purposes since most neurological disorders and brain aging problems remain substantially incurable. In the mammalian nervous system, neurons are mostly not renewed throughout life and cannot be replaced. In humans, the increasing life expectancy explains the increase in brain health problems, also producing heavy social and economic burden. An exception to the “static” brain is represented by stem cell niches leading to the production of new neurons. Such adult neurogenesis is dramatically reduced from fish to mammals, and in large-brained mammals with respect to rodents. Some examples of neurogenesis occurring outside the neurogenic niches have been reported, yet these new neurons actually do not integrate in the mature nervous tissue. Non-newly generated, “immature” neurons (nng-INs) are also present: Prenatally generated cells continuing to express molecules of immaturity (mostly shared with the newly born neurons). Of interest, nng-INs seem to show an inverse phylogenetic trend across mammals, being abundant in higher-order brain regions not served by neurogenesis and providing structural plasticity in rather stable areas. Both newly generated and nng-INs represent a potential reservoir of young cells (a “brain reserve”) that might be exploited for preventing the damage of aging and/or delay the onset/reduce the impact of neurological disorders.
... Bats show no adult DG neurogenesis for the majority of species studied (Amrein, 2015), though bats clearly exhibit hippocampal place cells, and spatio-contextual reasoning that is attributed to the hippocampus (Finkelstein et al., 2016). Numerous comparative studies have demonstrated heterogeneous adult neurogenesis rates across mammalian species that does not seem to depend on their need for spatial reasoning (Cavegn et al., 2013;Amrein, 2015;van Dijk et al., 2016). ...
Adult neurogenesis in the hippocampal dentate gyrus (DG) of mammals is known to contribute to memory encoding in many tasks. The DG also exhibits exceptionally sparse activity compared to other systems, however, whether sparseness and neurogenesis interact during memory encoding remains elusive. We implement a novel learning rule consistent with experimental findings of competition among adult-born neurons in a supervised multilayer feedforward network trained to discriminate between contexts. From this rule, the DG population partitions into neuronal ensembles each of which is biased to represent one of the contexts. This corresponds to a low dimensional representation of the contexts, whereby the fastest dimensionality reduction is achieved in sparse models. We then modify the rule, showing that equivalent representations and performance are achieved when neurons compete for synaptic stability rather than neuronal survival. Our results suggest that competition for stability in sparse models is well-suited to developing ensembles of what may be called memory engram cells.
