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The study of cortical cytoarchitectonics and the histology of the human cerebral cortex was pursued by many investigators in the second half of the nineteenth century, such as Jacob Lockhart Clarke, Theodor Meynert, and Vladimir Betz. Another of these pioneers, whose name has largely been lost to posterity, is considered here: Herbert Coddington Major (1850–1921). Working at the West Riding Asylum in Wakefield, United Kingdom, Major's thesis of 1875 described and illustrated six-layered cortical structure in both non-human primates and man, as well as "giant nerve cells" which corresponded to those cells previously described, but not illustrated, by Betz. Further journal publications by Major in 1876 and 1877 confirmed his finding of six cortical strata. However, Major's work was almost entirely neglected by his contemporaries, including his colleague and sometime pupil at the West Riding Asylum, William Bevan-Lewis (1847–1929), who later (1878) reported the presence of both pentalaminar and hexalaminar cortices. Bevan-Lewis's work was also later credited with the first illustration of Betz cells. [ABSTRACT FROM AUTHOR]

The Polish Institute for Brain Research was established in Warsaw in 1928 to support scientific research on the brain and its functions. The director of the institute was Maksymilian Rose (1883–1937), a distinguished Polish neurologist and neuroanatomist, a disciple of Oskar Vogt and Korbinian Brodmann. In 1931, the Institute was moved from Warsaw to Vilnius. The Institute was well-known in Europe at the time because of the research in the fields of neuroscience, clinical neurology, and psychiatry, as well as the cytoarchitectonic analysis of social activists’ brains—a fashionable, neophrenological way to link the mental functions of deceased geniuses with the cellular composition of their central nervous systems. In 1939, the work of the Institute was interrupted by World War II; some of the preparations and materials were moved from Vilnius to Warsaw, some were stored in Vilnius, and some were lost. In this article, we analyze the primary and secondary sources, some of which were obscure for over 80 years, and evaluate the most important scientific achievements of the Polish Institute for Brain Research, as well as its legacy in the early period of modern neuroscience and neurology in interwar Vilnius. [ABSTRACT FROM AUTHOR]

Disruption of neocortical circuitry and architecture in humans causes numerous neurodevelopmental disorders. Neocortical cytoarchitecture is orchestrated by various transcription factors such as Satb2 that control target genes during strict time windows. In humans, mutations of SATB2 cause SATB2 Associated Syndrome (SAS), a multisymptomatic syndrome involving epilepsy, intellectual disability, speech delay, and craniofacial defects. Here we show that Satb2 controls neuronal migration and callosal axonal outgrowth during murine neocortical development by inducing the expression of the GPI-anchored protein, Semaphorin 7A (Sema7A). We find that Sema7A exerts this biological activity by heterodimerizing in cis with the transmembrane semaphorin, Sema4D. We could also observe that heterodimerization with Sema7A promotes targeting of Sema4D to the plasma membrane in vitro. Finally, we report an epilepsy-associated de novo mutation in Sema4D (Q497P) that inhibits normal glycosylation and plasma membrane localization of Sema4D-associated complexes. These results suggest that neuronal use of semaphorins during neocortical development is heteromeric, and a greater signaling complexity exists than was previously thought. Disruption of neocortical circuitry and architecture causes neurodevelopmental disorders. Here the authors find that migration and axon projection of upper layer neurons are dependent on Sema7A-Sema4D heterodimerization, and that insufficient transcription of Sema7A or incomplete glycosylation of Sema4D inhibit these processes. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) are vital structural units of the cardiovascular system possessing two principal distinctive properties: heterogeneity and plasticity. Endothelial heterogeneity is defined by differences in tissue-specific endothelial phenotypes and their high predisposition to modification along the length of the vascular bed. This aspect of heterogeneity is closely associated with plasticity, the ability of ECs to adapt to environmental cues through the mobilization of genetic, molecular, and structural alterations. The specific endothelial cytoarchitectonics facilitate a quick structural cell reorganization and, furthermore, easy adaptation to the extrinsic and intrinsic environmental stimuli, known as the epigenetic landscape. ECs, as universally distributed and ubiquitous cells of the human body, play a role that extends far beyond their structural function in the cardiovascular system. They play a crucial role in terms of barrier function, cell-to-cell communication, and a myriad of physiological and pathologic processes. These include development, ontogenesis, disease initiation, and progression, as well as growth, regeneration, and repair. Despite substantial progress in the understanding of endothelial cell biology, the role of ECs in healthy conditions and pathologies remains a fascinating area of exploration. This review aims to summarize knowledge and concepts in endothelial biology. It focuses on the development and functional characteristics of endothelial cells in health and pathological conditions, with a particular emphasis on endothelial phenotypic and functional heterogeneity. [ABSTRACT FROM AUTHOR]

Cytoarchitecture, the organization of cells within organs and tissues, serves as a crucial anatomical foundation for the delineation of various regions. It enables the segmentation of the cortex into distinct areas with unique structural and functional characteristics. While traditional 2D atlases have focused on cytoarchitectonic mapping of cortical regions through individual sections, the intricate cortical gyri and sulci demands a 3D perspective for unambiguous interpretation. In this study, we employed fluorescent micro-optical sectioning tomography to acquire architectural datasets of the entire macaque brain at a resolution of 0.65 µm × 0.65 µm × 3 µm. With these volumetric data, the cortical laminar textures were remarkably presented in appropriate view planes. Additionally, we established a stereo coordinate system to represent the cytoarchitectonic information as surface-based tomograms. Utilizing these cytoarchitectonic features, we were able to three-dimensionally parcel the macaque cortex into multiple regions exhibiting contrasting architectural patterns. The whole-brain analysis was also conducted on mice that clearly revealed the presence of barrel cortex and reflected biological reasonability of this method. Leveraging these high-resolution continuous datasets, our method offers a robust tool for exploring the organizational logic and pathological mechanisms of the brain's 3D anatomical structure. [ABSTRACT FROM AUTHOR]

The mesial piriform region plays a central role in olfaction. Its small size and complex geometry, however, make it a difficult target in functional neuroimaging studies, while histological maps often represent schematic drawings, which are not compatible with requirements for modern imaging. To bridge this gap, cytoarchitectonic analysis and mapping of the region was performed in serial histological sections over their full extent in 10 postmortem brains. The temporobasal areas PirTBd and PirTBv and temporal areas PirTu and PirTit were identified and analyzed. Probabilistic cytoarchitectonic maps of the piriform areas in MNI reference space and high-resolution maps of the amygdala-piriform region on the BigBrain model were calculated as part of the Julich-Brain. Differences in the cytoarchitectonic "texture" of the region were quantified based on the Gray Level Co-Occurrence Matrix. Results showed that allocortical areas were not consistently associated with the rostral Limen insulae, although it was often suggested as a landmark in neuroimaging protocols. PirTu was associated with the uncal tip. PirTit was the largest area, reaching to the temporal pole, with a "temporal" (caudal) and a "temporopolar" (rostral) part having complex neighborhood relationships. The probabilistic maps reflect interindividual variability; they are openly available via the digital EBRAINS platform to serve as an anatomical reference for studies related to olfaction. [ABSTRACT FROM AUTHOR]

In multicolor fluorescence microscopy, it is crucial to orient biological structures at a single-cell resolution based on precise anatomical annotations of cytoarchitecture images. However, during synchronous multicolor imaging, due to spectral mixing, the crosstalk from the blue signals of 4′,6-diamidino-2-phenylindole (DAPI)-stained cytoarchitecture images to the green waveband hinders the visualization and identification of green signals. Here, we proposed a deep learning-based framework named the crosstalk elimination and cytoarchitecture enhancement pipeline (CECEP) to simultaneously acquire crosstalk-free signals in the green channel and high-contrast DAPI-stained cytoarchitecture images during multicolor fluorescence imaging. For the CECEP network, we proposed an unsupervised learning algorithm named the cytoarchitecture enhancement network (CENet), which increased the signal-to-background ratio (SBR) of the cytoarchitecture images from 1.5 to 15.0 at a reconstruction speed of 25 Hz for 1800 × 1800 pixel images. The CECEP network is widely applicable to images of different quality, different types of tissues, and different multicolor fluorescence microscopy. In addition, the CECEP network can also facilitate various downstream analysis tasks, such as cell recognition, structure tensor calculation, and brain region segmentation. With the CECEP network, we simultaneously acquired two specific fluorescence-labeled neuronal distributions and their colocated high-SBR cytoarchitecture images without crosstalk throughout the brain. Experimental results demonstrate that our method could potentially facilitate multicolor fluorescence imaging applications in biology, such as revealing and visualizing different types of biological structures with precise locations and orientations. [ABSTRACT FROM AUTHOR]

The ultrastructural differences are shown between the cytoarchitecture of the excretory bladder and excretory inclusions in four digenean species, two azygiids, the marine Otodistomum cestoides and the freshwater Azygia lucii , the marine derogenid Derogenes varicus and the freshwater allocreadiid Acrolichanus auriculatus. The unusual cytoarchitecture of the bladder epithelium of the azygiid digeneans, consisting along its entire length of two alternating, morphologically different zones, tegumental and cellular excretory epithelial zones, connected by septate junctions, has recorded for the first time for the Digenea and, in general, for the Neodermata. It, possible, suggests the participation of the tegumental distal cytoplasmic layer in the formation of their excretory bladder epithelium. Like most digeneans, the excretory bladder of A. auriculatus and D. varicus has a syncytial epithelial lining. Based on available literature and our own results, we can confirm the presence of the excretory corpuscles in adult marine digeneans and their absence from freshwater species, regardless of the digenean localization in their host. The present study shown that in marine digeneans, the excretory corpuscles are associated with specialized excretory cells or excretory syncytial epithelium. Ultrastructural data were obtained on the possible growth of the excretory bladder epithelium due to the migration of undifferentiated cells into the epithelial lining in studied marine species. We may assume that the bladder epithelium of marine adult digeneans specializes, in addition to the excretory function, in osmoregulatory function. [ABSTRACT FROM AUTHOR]

Animals collect and process the information they need to survive and reproduce. The means by which they process information is through the capacity of intelligence, which is in turn a function of the brain, its morphology, size, organization, and cytoarchitecture. While the internal organization and cellular interconnectivity of the brains of fossilized animals are invisible to paleontologists, the size and surface morphology of the brain are sometimes preserved, usually only in part, in the form of endocasts (casts, either natural or artificial, of the inside of the brain case). This broad survey of the evolution of intelligence in primates as interpreted from the fossil record of endocasts is primarily focused on the lineages that inform us more directly about the evolutionary events leading to the origin of human intelligence. [ABSTRACT FROM AUTHOR]

The primary afferent system in the rat's spinal cord starts to develop in the third last week of gestation. First, the pseudounipolar DRG neurons extend their centripetal long primary axons, targeting rostral supra-segmental nuclei in the spinal cord. Meanwhile, the subsequent innervation of the juxta- and intra-segmental spinal levels enables the three subdivisions to commence integrating a complex network with the body periphery. This process may continue to refine and adapt the system life-long. The experimental data elucidated the steps involved in developing the cytoarchitecture by separating the axons of the long and intermediate subdivisions from the short subdivision. Here, we present a blueprint of the features of the long primary afferent axons developing in sequential waves. The pioneering long afferent axons targeted the dorsal gracile nuclei at spring tide and Clarke's nuclei at neap tide in ventrally bent trajectories. The paradigm's myelotomy blocked these pioneering fibers from stepping down the developmental cascade, rendering an unknown phenotype. This reflected a hypothetical transition hub stationed on the assembly line, delineating a critical period. The paradigm also affected the neuropil's ripening independently from the long primary afferent system. The data disclosed that fetal hyposaturation yielded an in vivo genomic engineering capability. Fetal tissue was susceptible to hyposaturation, showing remarkable versatility early in fetal life. The translational impact may favor research into the elusive etiology of clinical syndromes concerning the afferent system relating to fetal hyposaturation. [ABSTRACT FROM AUTHOR]

It is unclear whether differences between the two brain hemispheres become larger or smaller with increasing age. Given that the hippocampus is particularly susceptible to age-related changes, here, we set out to investigate the correlation between chronological age and hippocampal asymmetry, both for the hippocampal complex as a whole and in cytoarchitectonically defined subregions (cornu ammonis 1, 2, 3, dentate gyrus, subiculum, and entorhinal cortex). We analyzed T1-weighted data of the brain from a sample of 725 healthy individuals (406 women/319 men) spanning a wide age range (36–100 years) from The Lifespan Human Connectome Project in Aging. Correlations between the absolute asymmetry index and chronological age were positive for all six subregions and also for the hippocampal complex as a whole, albeit effects the effects were not significant for the dentate gyrus. This suggests that, overall, hippocampal asymmetry increases with increasing age (i.e., the left and right hippocampi become more different over time). Given that the subregions of the hippocampal complex serve different brain functions, follow-up research is needed to explore the functional implications within the framework of brain aging. In addition, longitudinal studies will be necessary to confirm the observed cross-sectional effects. [ABSTRACT FROM AUTHOR]

The human isocortex consists of tangentially organized layers with unique cytoarchitectural properties. These layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support function through enabling targeted corticocortical connections. Here, leveraging maps of the 6 cortical layers based on 3D human brain histology, we aimed to quantitatively characterize the systematic covariation of laminar structure in the cortex and its functional consequences. After correcting for the effect of cortical curvature, we identified a spatial pattern of changes in laminar thickness covariance from lateral frontal to posterior occipital regions, which differentiated the dominance of infra- versus supragranular layer thickness. Corresponding to the laminar regularities of cortical connections along cortical hierarchy, the infragranular-dominant pattern of laminar thickness was associated with higher hierarchical positions of regions, mapped based on resting-state effective connectivity in humans and tract-tracing of structural connections in macaques. Moreover, we show that regions with similar laminar thickness patterns have a higher likelihood of structural connections and strength of functional connections. In sum, here, we characterize the organization of laminar thickness in the human isocortex and its association with cortico-cortical connectivity, illustrating how laminar organization may provide a foundational principle of cortical function. The human isocortex consists of tangentially organized layers with unique cytoarchitectural properties. This study shows that the regional variation of high-resolution histology-based laminar thickness profiles in the human isocortex is associated with the cortical connectome and hierarchical organization. [ABSTRACT FROM AUTHOR]

The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretion and/or counter-regulatory influence leads to diabetes. Debate in the field centers on the cytoarchitecture of islets, as the signaling that governs hormonal secretion depends on structural and functional factors, including electrical connectivity, innervation, vascularization, and physical proximity. Much effort has therefore been devoted to elucidating which architectural features are significant for function and how derangements in these features are correlated or causative for dysfunction, especially using quantitative network science or graph theory characterizations. Here, we ask if there are non-local features in islet cytoarchitecture, going beyond standard network statistics, that are relevant to islet function. An example is ring structures, or cycles, of α and δ cells surrounding β cell clusters or the opposite, β cells surrounding α and δ cells. These could appear in two-dimensional islet section images if a sphere consisting of one cell type surrounds a cluster of another cell type. To address these issues, we developed two independent computational approaches, geometric and topological, for such characterizations. For the latter, we introduce an application of topological data analysis to determine locations of topological features that are biologically significant. We show that both approaches, applied to a large collection of islet sections, are in complete agreement in the context both of developmental and diabetes-related changes in islet characteristics. The topological approach can be applied to three-dimensional imaging data for islets as well. Author summary: The pancreatic islets or islets of Langerhans are regions of the pancreas that contain endocrine or hormone-producing cells classified as alpha, beta, delta, PP, and epsilon. They are responsible for regulating blood glucose levels, and their dysfunction leads to diabetes. Differences in relative arrangement of alpha, beta, and delta cells has been observed between species. For example, mouse islets predominantly contain beta cells in the central core with alpha and delta cells forming a mantle around them localized in the periphery. Similar arrangement has been seen in small human islets, but larger islets have alpha and delta cells also along the vessels penetrating inside the islet. These findings motivate the debate of the functional significance of these structural patterns. In this work we mathematically define and implement quantitation of ring-structures or cycles of alpha and delta cells around beta cells (and vice versa) using two distinct methods, geometric and topological, in 2D sections of islets. We analyze two different data sets of 2D sections of human islets, one from different developmental stages and another from control and diabetic subjects. Further, we illustrate extension of the topological method to three dimensional data sets. [ABSTRACT FROM AUTHOR]

• Anterior insular ictal symptoms combine autonomic, oro-pharyngeal, emotional symptoms and the "hand-to-throat" sign. • Posterior insular seizures imply somatosensory symptoms including pain and cephalic sensations. • Middle insular seizures combine anterior and posterior insular seizure features. To describe pure insular ictal semiology and patterns of extra-insular spread demonstrated by stereoelectroencephalography (SEEG) according to a classification based on the insular cytoarchitecture. We investigated the ictal semiology in 17 patients undergoing SEEG for insular epilepsy. The insular cortex was divided into three regions roughly overlapping with the agranular, dysgranular and granular regions. Ictal semiology was described accordingly: anterior insula (AI, short anterior and middle gyri), middle insula (MI, short posterior and long anterior gyri) and posterior insula (PI, long posterior gyrus). Awareness impairment occurred secondarily to extra-insular ictal spread. Subjective manifestations were constant. AI seizures (n = 3) presented with autonomic (increased heart rate [HR], respiratory changes), oropharyngeal (mainly throat sensations), emotional (fear, anguish) semiology and the "hand-to-throat" sign followed by frontal-like semiology. MI seizures (n = 8) presented with mainly non-painful paresthesia, some autonomic (respiratory, increased HR), oropharyngeal or thermic symptoms and early motor features with spread to the opercular cortex. PI seizures (n = 6) were characterized by somatosensory semiology, mainly paresthesia potentially painful, and cephalic sensations. Cytoarchitectonic-based classification and the corresponding ictal features support the antero-posterior grading of insular seizures and highlight specific ictal symptoms. This refinement of insular semiology can help optimize the planning of SEEG for presumed insular epilepsy. [ABSTRACT FROM AUTHOR]

The hypothalamus (“hypo” meaning below, and “thalamus” meaning bed) consists of regulatory circuits that support basic life functions that ensure survival. Sitting at the interface between peripheral, environmental, and neural inputs, the hypothalamus integrates these sensory inputs to influence a range of physiologies and behaviors. Unlike the neocortex, in which a stereotyped cytoarchitecture mediates complex functions across a comparatively small number of neuronal fates, the hypothalamus comprises upwards of thousands of distinct cell types that form redundant yet functionally discrete circuits. With single-cell RNA sequencing studies revealing further cellular heterogeneity and modern photonic tools enabling high-resolution dissection of complex circuitry, a new era of hypothalamic mapping has begun. Here, we provide a general overview of mammalian hypothalamic organization, development, and connectivity to help welcome newcomers into this exciting field. [ABSTRACT FROM AUTHOR]

The intricate, crystalline cytoarchitecture of the mammalian organ of Corti presumably plays an important role in cochlear amplification. As currently understood, the oblique, Y-shaped arrangement of the outer hair cells (OHCs) and phalangeal processes of the Deiters cells serves to create differential “push–pull” forces that drive the motion of the basilar membrane via the spatial feedforward and/or feedbackward of OHC forces. In concert with the cochlear traveling wave, the longitudinal separation between OHC sensing and forcing creates phase shifts that yield a form of negative damping, amplifying waves as they propagate. Unlike active forces that arise and act locally, push– pull forces are inherently directional—whereas forward-traveling waves are boosted, reverse-traveling waves are squelched. Despite their attractions, models based on push– pull amplification must contend with otoacoustic emissions (OAEs), whose existence implies that amplified energy escapes from the inner ear via mechanisms involving reverse traveling waves. We analyze hybrid local/push–pull models to determine the constraints that reflection-source OAEs place on the directionality of cochlear wave propagation. By implementing a special force-mixing control knob, we vary the mix of local and push–pull forces while leaving the forward-traveling wave unchanged. Consistency with stimulus-frequency OAEs requires that the active forces underlying cochlear wave amplification be primarily local in character, contradicting the prevailing view. By requiring that the oblique cytoarchitecture produce predominantly local forces, we reinterpret the functional role of the Y-shaped geometry, proposing that it serves not as a push–pull amplifier, but as a mechanical funnel that spatially integrates local OHC forces. [ABSTRACT FROM AUTHOR]

We studied the effect of amphotericin B (2.5×10–5 and 5.4×10–5 M) on osmotic resistance and surface cytoarchitectonics of donor blood erythrocytes. Antibiotic at a concentration of 2.5×10–5 M induced most pronounced changes in the studied parameters, which can be related to the specifics of the spatial organization of the cholesterol–amphotericin B complexes at different stoichiometric ratios of the components and their ability to pore formation in the membranes. Cholesterol binding to the polyene antibiotic and the appearance of perforations in the plasma membrane lead to accumulation of reversibly and irreversibly deformed cells and their hemolysis. The appearance of a large number of irreversibly deformed erythrocytes indicates an impaired ability to elastic deformation in the microcirculatory stream, which can lead to disruption of their functions in vivo and intravascular hemolysis. [ABSTRACT FROM AUTHOR]

Ventilator-induced diaphragm dysfunction (VIDD) is a common sequela of intensive care unit (ICU) treatment requiring mechanical ventilation (MV) and neuromuscular blockade (NMBA). It is characterised by diaphragm weakness, prolonged respirator weaning and adverse outcomes. Dissociative glucocorticoids (e.g., vamorolone, VBP-15) and chaperone co-inducers (e.g., BGP-15) previously showed positive effects in an ICU-rat model. In limb muscle critical illness myopathy, preferential myosin loss prevails, while myofibrillar protein post-translational modifications are more dominant in VIDD. It is not known whether the marked decline in specific force (force normalised to cross-sectional area) is a pure consequence of altered contractility signaling or whether diaphragm weakness also has a structural correlate through sterical remodeling of myofibrillar cytoarchitecture, how quickly it develops, and to which extent VBP-15 or BGP-15 may specifically recover myofibrillar geometry. To address these questions, we performed label-free multiphoton Second Harmonic Generation (SHG) imaging followed by quantitative morphometry in single diaphragm muscle fibres from healthy rats subjected to five or 10 days of MV + NMBA to simulate ICU treatment without underlying confounding pathology (like sepsis). Rats received daily treatment of either Prednisolone, VBP-15, BGP-15 or none. Myosin-II SHG signal intensities, fibre diameters (FD) as well as the parameters of myofibrillar angular parallelism (cosine angle sum, CAS) and in-register of adjacent myofibrils (Vernier density, VD) were computed from SHG images. ICU treatment caused a decline in FD at day 10 as well as a significant decline in CAS and VD from day 5. Vamorolone effectively recovered FD at day 10, while BGP-15 was more effective at day 5. BGP-15 was more effective than VBP-15 in recovering CAS at day 10 although not to control levels. In-register VD levels were restored at day 10 by both compounds. Our study is the first to provide quantitative insights into VIDD-related myofibrillar remodeling unravelled by SHG imaging, suggesting that both VBP-15 and BGP-15 can effectively ameliorate the structure-related dysfunction in VIDD. [ABSTRACT FROM AUTHOR]

The hippocampus is a center of learning, memory, and spatial navigation. This region is divided into the CA1, CA2, and CA3 areas, which are anatomically different from each other. Among these divisions, the CA2 area is unique in terms of functional relevance to sociality. The CA2 area is often manually detected based on the size, shape, and density of neurons in the hippocampal pyramidal cell layer, but this manual segmentation relying on cytoarchitecture is impractical to apply to a large number of samples and dependent on experimenters' proficiency. Moreover, the CA2 area has been defined based on expression pattern of molecular marker proteins, but it generally takes days to complete immunostaining for such proteins. Thus, we asked whether the CA2 area can be systematically segmented based on cytoarchitecture alone. Since the expression pattern of regulator of G-protein signaling 14 (RGS14) signifies the CA2 area, we visualized the CA2 area in the mouse hippocampus by RGS14- immunostaining and Nissl-counterstaining and manually delineated the CA2 area. We then established "CAseg," a machine learning-based automated algorithm to segment the CA2 area with the F1-score of approximately 0.8 solely from Nisslcounterstained images that visualized cytoarchitecture. CAseg was extended to the segmentation of the prairie vole CA2 area, which raises the possibility that the use of this algorithm can be expanded to other species. Thus, CAseg will be beneficial for investigating unique properties of the hippocampal CA2 area. [ABSTRACT FROM AUTHOR]

During the period extending from 1900 to 1970, Oskar and Cécile Vogt and their numerous collaborators ('the Vogt–Vogt school') published a large number of studies on the myeloarchitecture of the human cerebral cortex. During the last decade, we have concerned ourselves with a detailed meta-analysis of these now almost totally forgotten studies, with the aim to bringing them into the modern era of science. This scrutiny yielded inter alia a myeloarchitectonic map of the human neocortex, showing a parcellation into 182 areas (Nieuwenhuys et al. in Brain Struct Funct 220:2551–2573, 2015; Erratum in Brain Struct Funct 220: 3753–3755, 2015). This map, termed 2D'15, which is based on data derived from all of the 20 publications constituting the myeloarchitectonic legacy of the Vogt–Vogt school, has the limitation that it is two-dimensional i.e. it shows only the parts of the cortex exposed at the free surface of the cerebral hemispheres and not the extensive stretches of cortex hidden in the cortical sulci. However, a limited set of data, derived from four of the 20 publications available, has enabled us to create a 3D map, showing the myeloarchitectonic parcellation of the entire human neocortex. This map, designated as 3D′23, contains 182 areas: 64 frontal, 30 parietal, 6 insular, 19 occipital and 63 temporal. We have also prepared a 2D version (2D′23), of this 3D′23 map to serve as a link between the latter and our original 2D′15 map. Detailed comparison of the parcellations visualized in our three maps (2D′15, 2D′23 and 3D′23) warrants the conclusion that our new 3D′23 map may be considered as representative for the entire myeloarchitectural legacy of the Vogt–Vogt School. Hence it is now possible to compare the rich amount of myeloarchitectonic data assembled by that school directly with the results of current 3D analyses of the architecture of the human cortex, such as the meticulous quantitative cyto- and receptor architectonic studies of Zilles, Amunts and their numerous associates (Amunts et al. in Science 369:988–992, 2020), and the multimodal parcellation of the human cortex based on magnetic resonance images from the Human Connectome Project, performed by Glasser et al. in Nature 536:171–178, 2016). [ABSTRACT FROM AUTHOR]

The use of enzyme preparations is a traditional trend in various fields of medicine. The usage of immobilized enzymes hyaluronidase (IG) and subtilisin (IS) seems to be very promising for the treatment of damage to the ocular surface. The aim of the study was to establish the nature of changes in the ultrastructural organization of human conjunctival epithelium under the influence of immobilized hyaluronidase and subtilisin in vitro. Material and methods. In the experiment, a culture of normal cells of the human conjunctiva Chanqconjunctiva, clone 1–5 C-4, was seeded in 96well plates in the amount of 2 × 104 cells/well, after 24 h the medium was removed, Eagle’s medium MEM and fetal calf serum were added and cells were cultured for another 48 h. 5 experimental groups were formed: group 1 – without drugs (except for the composition of the incubation scheme), groups 2 and 3 – with IS at a concentration of 37 and 150 U/ml, respectively, groups 4 and 5 – with IG at a concentration of 37 and 150 U/ml, respectively. After preparation of cell preparations under a JEM 1400 electron microscope (Japan), ultrathin sections of 70–100 nm were studied at ×1000 magnification. Results. The article presents the results of electron microscopy of a culture of normal cells of the human conjunctiva in 5 experimental groups of cells with a description of changes in cytoarchitectonics under the influence of IG and IS. Conclusions. The introduction of immobilized enzymes into human conjunctival cell culture at a low dose (37 U/ml) affects the organization of cells without cytotoxic effects, while increasing the dose directly correlates with the occurrence of a cytotoxic effect.

This correction notice addresses an error in Figure 5 and Supplementary Figure S2A of the original publication titled "Memory Impairment, Pro-Inflammatory Host Response and Brain Histopathologic Severity in Rats Infected with K. pneumoniae or P. aeruginosa Meningitis." The mistake was in the sub-image of the first row, fourth column in Figure 5, and the value of granular layer thickness in the hippocampus on day 5 in Figure S2A. The corrected figures are provided in the notice. The authors assure that the scientific conclusions remain unaffected. [Extracted from the article]

The mouse brain is by far the most intensively studied among mammalian brains, yet basic measures of its cytoarchitecture remain obscure. For example, quantifying cell numbers, and the interplay of sex, strain, and individual variability in cell density and volume is out of reach for many regions. The Allen Mouse Brain Connectivity project produces high-resolution full brain images of hundreds of brains. Although these were created for a different purpose, they reveal details of neuroanatomy and cytoarchitecture. Here, we used this population to systematically characterize cell density and volume for each anatomical unit in the mouse brain. We developed a DNN-based segmentation pipeline that uses the autofluorescence intensities of images to segment cell nuclei even within the densest regions, such as the dentate gyrus. We applied our pipeline to 507 brains of males and females from C57BL/6J and FVB.CD1 strains. Globally, we found that increased overall brain volume does not result in uniform expansion across all regions. Moreover, region-specific density changes are often negatively correlated with the volume of the region; therefore, cell count does not scale linearly with volume. Many regions, including layer 2/3 across several cortical areas, showed distinct lateral bias. We identified strain-specific or sex-specific differences. For example, males tended to have more cells in extended amygdala and hypothalamic regions (MEA, BST, BLA, BMA, and LPO, AHN) while females had more cells in the orbital cortex (ORB). Yet, inter-individual variability was always greater than the effect size of a single qualifier. We provide the results of this analysis as an accessible resource for the community. [ABSTRACT FROM AUTHOR]

Human cortical organoids (hCOs), derived from human induced pluripotent stem cells (iPSCs), provide a platform to interrogate mechanisms of human brain development and diseases in complex three- dimensional tissues. However, current hCO development methods lack important non-neural tissues, such as the surrounding meningeal layer, that have been shown to be essential for normal corticogenesis and brain development. Here, we first generated hCOs from a single rosette to create more homogenous organoids with consistent size around 250 µm by day 5. We then took advantage of a 3D co-culture system to encapsulate brain organoids with a thin layer of meningeal cells from the very early stages of cortical development. Immunostaining analysis was performed to display different cortical layer markers during different stages of development. Real-time monitoring of organoid development using IncuCyte displayed enhanced morphology and increased growth rate over time. We found that meningeal-encapsulated organoids illustrated better laminar organization by exhibiting higher expression of REELIN by Cajal–Retzius neurons. Presence of meningeal cells resulted in a greater expansion of TBR2 intermediate progenitor cells (IPCs), the deep cortical layer (CTIP2) and upper cortical layer (BRN2). Finally, meningeal-encapsulated organoids enhanced outer radial glial and astrocyte formation illustrated by stronger expression of HOPX and GFAP markers, respectively. This study presents a novel 3D co-culture platform to more closely mimic the in vivo cortical brain structure and enable us to better investigating mechanisms underlying the neurodevelopmental disorders during embryonic development. [ABSTRACT FROM AUTHOR]

The complexity of the tissue is mainly due to the fact that bone is the result of a permanent process of osteogenesis and bone resorption, and the balance between these two processes ensures the health of the tissue. This balance, as it has been shown, can be influenced by a very large number of factors, and most evidence supports the importance and role of the hormonal factor as one of the main determinants in the development of osteoporosis. Alongside this, it is important to assess the influence that chronic medication, such as lipid-lowering medication can have on bone tissue, besides the hormonal factor. Osteoporosis, the main chronic pathology of bone tissue, is assessed from the perspective of bone mineral density, but this assessment cannot provide information on the cytoarchitectonics of bone tissue, which is particularly important when talking about bone as a resistance structure, since the main complication of osteoporosis is the fracture produced on pathological bone. The measurement of 2D T2-T2 molecular exchange maps allows the assessment of bone tissue cytoarchitectonics because it offers the possibility to appreciate both the pores and their communication, thus providing a picture of the resistance that a bone structure may have under the influence of hormonal factors, correlated or not with various medications that may influence the organic matrix or inorganic component of bone tissue. [ABSTRACT FROM AUTHOR]

Mudskippers are intertidal burrowing fish with unique living habits. So far, studies on the cytoarchitecture of the brain in fish with such behaviors remain limited. Therefore, documenting the neuroanatomy of this animal is of interest because of its unique characteristics. In this study, we examined the cytoarchitecture of mudskipper (Boleophthalmus pectinirostris) brain and investigated whether it has any peculiarities in its brain structures. In general, the basic composition, morphology, and organization of mudskipper brain do not vary markedly from those of other teleosts. The main differences appear in the telencephalon and diencephalon. In addition to Nissl staining, immunostainings for catecholaminergic and cholinergic systems were performed to help identify certain nuclei. The results showed that the number of subdivisions of the central division of pallium, lateral division of pallium, and medial division of pallium were different with other teleost species. In addition, some diencephalic nuclei, including the nucleus subglomerulosus, lateral thalamic nucleus, and intermediate superficial pretectal nucleus, were absent, which suggests the corresponding functions, such as visual or gustatory function, are less developed or specialized in B. pectinirostris. These results will provide a fundamental neuroanatomical basis for future studies on neuroendocrine regulation of behavior in intertidal burrowing fish. [ABSTRACT FROM AUTHOR]

Introduction: The subventricular zone (SVZ) represents one of the main adult brain neurogenesis niche. In-vivo imaging of SVZ is very challenging and little is known about MRI correlates of SVZ macro- and micro-structural injury in multiple sclerosis (MS) patients Methods: The aim of the present study is to evaluate differences in terms of volume and microstructural changes [as assessed with the novel Spherical Mean Technique (SMT) model, evaluating: Neurite Signal fraction (INTRA); Extra-neurite transverse (EXTRATRANS) and mean diffusivity (EXTRAMD)] in SVZ between relapsing-remitting (RR) or progressive (P) MS patients and healthy controls (HC). We are also going to explore whether SVZ microstructural injury correlate with caudate (a nucleus that is in the vicinity of the SVZ) or thalamus (another welldefined grey matter area which is further from SVZ than caudate) volume and clinical disability. Clinical and brain MRI data were prospectively acquired from 20 HC, 101 RRMS, and 50 PMS patients. Structural and diffusion metrics inside the global SVZ, normal appearing (NA-) SVZ, caudate and thalamus were collected. Results: We found a statistically significant difference between groups in terms of NA-SVZ EXTRAMD (PMS>RRMS>HC; p = 0.002), EXTRATRANS (PMS>RRMS>HC; p<0.0001), and INTRA (HC>RRMS>PMS; p = 0.009). Multivariable models showed that NA-SVZ metrics significantly predicted caudate (R2 = 0.21, p < 0.0001), but not thalamus, atrophy. A statistically significant correlation between EXTRAMD and EXTRATRANS of the NA-SVZ and EDSS (r=0.25, p=0.003 and r=0.24, p = 0.003, respectively) was found. These findings were confirmed in analyses restricted to RRMS, but not to PMS patients. Discussion: In conclusion, the microstructural damage we observed within the NA-SVZ of MS patients - reflecting higher free water content (higher EXTRAMD), cytoarchitecture disruption and astrogliosis (higher EXTRATRANS and lower INTRA) - was more evident in the progressive as compared to the relapsing phases of MS. These abnormalities were significantly associated with a more pronounced caudate atrophy and higher clinical disability scores. Our findings may support the neuroprotective role of SVZ in MS patients. [ABSTRACT FROM AUTHOR]

The complexity of the cerebral cortex underlies its function and distinguishes us as humans. Here, we present a principled veridical data science methodology for quantitative histology that shifts focus from image-level investigations towards neuron-level representations of cortical regions, with the neurons in the image as a subject of study, rather than pixel-wise image content. Our methodology relies on the automatic segmentation of neurons across whole histological sections and an extensive set of engineered features, which reflect the neuronal phenotype of individual neurons and the properties of neurons' neighborhoods. The neuron-level representations are used in an interpretable machine learning pipeline for mapping the phenotype to cortical layers. To validate our approach, we created a unique dataset of cortical layers manually annotated by three experts in neuroanatomy and histology. The presented methodology offers high interpretability of the results, providing a deeper understanding of human cortex organization, which may help formulate new scientific hypotheses, as well as to cope with systematic uncertainty in data and model predictions. [ABSTRACT FROM AUTHOR]

This review focuses on cytoarchitectonics and receptor architectonics as biological correlates of function and connectivity. It introduces the 3-dimensional cytoarchitectonic probabilistic maps of cortical areas and nuclei of the Julich-Brain Atlas, available at EBRAINS, to study structure-function relationships. The maps are linked to the BigBrain as microanatomical reference model and template space. The siibra software tool suite enables programmatic access to the maps and to receptor architectonic data that are anchored to brain areas. Such cellular and molecular data are tools for studying magnetic resonance connectivity including modeling and simulation. At the end, we highlight perspectives of the Julich-Brain as well as methodological considerations. Thus, microstructural maps as part of a multimodal atlas help elucidate the biological correlates of large-scale networks and brain function with a high level of anatomical detail, which provides a basis to study brains of patients with psychiatric disorders. [ABSTRACT FROM AUTHOR]

The parcellation of the primate cerebral cortex into numbered regions, based on cytoarchitecture, has greatly helped neuroscientists in our quest to understand how the brain implements cognition. Nonetheless, these maps provide an unnecessarily constraining view of how we should do functional neuroanatomy. It is time to think more broadly. Doing so will help advance the goal of incorporating ideas about emergentist organization and interactional complexity into neuroscience. [ABSTRACT FROM AUTHOR]

Tumor-to-tumor metastasis is a rare event which it is specifically up to pathologists to bring to light correctly. The histological identification of such tumor-to-tumor cases is simple when the respective histologies are different but can be problematic if the case includes two carcinomas with similar cytoarchitecture viewed one inside the other under the microscope. We report four cases of this condition in which clear cell renal cell carcinoma is involved, either as a receptor or as a donor, and remark on the difficulties in recognizing some of them. Appropriate clinical–pathological correlation, including a review of the patient's antecedents and radiological exams, would be a great help in routinely identifying tumor-to-tumor metastases. [ABSTRACT FROM AUTHOR]

Lesion localization is the basis for understanding neurologic disease, which is predicated on neuroanatomical knowledge carefully cataloged from histology and imaging atlases. However, it is often difficult to correlate clinical images of brainstem injury obtained by MRI scans with the details of human brainstem neuroanatomy represented in atlases, which are mostly based on cytoarchitecture using Nissl stain or a single histochemical stain, and usually do not include the cerebellum. Here, we report a high-resolution (200μm) 7T MRI of a cadaveric male human brainstem and cerebellum paired with detailed, co-registered histology (at 2 μm single cell resolution) of the immunohistochemically stained cholinergic, serotonergic, and catecholaminergic (dopaminergic, noradrenergic, and adrenergic) neurons, in relationship to each other and to the cerebellum. These immunohistochemical findings provide novel insights into the spatial relationships of brainstem cell types and nuclei, including subpopulations of melanin and TH+ neurons, and allows for more informed structural annotation of cell groups. Moreover, the co-registered MRI-paired histology helps validate imaging findings. This is useful for interpreting both scans and histology, and to understand the cell types affected by lesions. Our detailed chemoarchitecture and cytoarchitecture with corresponding high-resolution MRI builds on previous atlases of the human brainstem and cerebellum, and makes precise identification of brainstem and cerebellar cell groups involved in clinical lesions accessible for both laboratory scientists and clinicians alike. [ABSTRACT FROM AUTHOR]

The parietal lobe is a region of especially pronounced change in human brain evolution. Based on comparative neuroanatomical studies, the inferior parietal lobe (IPL) has been shown to be disproportionately larger in humans relative to chimpanzees and macaques. However, it remains unclear whether the underlying histological architecture of IPL cortical areas displays human-specific organization. Chimpanzees are among the closest living relatives of humans, making them an ideal comparative species to investigate potential evolutionary changes in the IPL. We parcellated the chimpanzee IPL using cytoarchitecture and myeloarchitecture, in combination with quantitative comparison of cellular features between the identified cortical areas. Four major areas on the lateral convexity of the chimpanzee IPL (PF, PFG, PG, OPT) and two opercular areas (PFOP, PGOP) were identified, similar to what has been observed in macaques. Analysis of the quantitative profiles of cytoarchitecture showed that cell profile density was significantly different in a combination of layers III, IV, and V between bordering cortical areas, and that the density profiles of these six areas supports their classification as distinct. The similarity to macaque IPL cytoarchitecture suggests that chimpanzees share homologous IPL areas. In comparison, human rostral IPL is reported to differ in its anatomical organization and to contain additional subdivisions, such as areas PFt and PFm. These changes in human brain evolution might have been important as tool making capacities became more complex. [ABSTRACT FROM AUTHOR]

Obtaining precise and detailed parcellations of the human brain has been a major focus of neuroscience research. Here, we present a multimodal dataset, MYATLAS, based on histology-derived myeloarchitectonic parcellations for use with contemporary neuroimaging analyses software. The core of MYATLAS is a novel 3D neocortical, surface-based atlas derived from legacy myeloarchitectonic histology studies. Additionally, we provide digitized quantitative laminar profiles of intracortical myelin content derived from postmortem photometric data, cross-correlated with in vivo myeloarchitectonic features obtained by quantitative MRI mapping. Moreover, congregated, digitized and quality-improved Vogt-Vogt legacy histology data is made available. Finally, to allow for cross-modality correlations, maps of quantitative myelin estimates and corresponding von Economo-Koskinas’ cytoarchitectonic features are also included. We share all necessary surface and volume-based registration files as well as shell scripts to facilitate applications of MYATLAS to future in vivo MRI studies.

The article presents a study which examined the amount of energy required to propagate dynamics across the sensory-fugal axis using network control theory. Topics discussed include mapping trans-hierachical state transitions, gradient of cytoarchitecture constrains the flow of activity over the cortex, and asymmetries in trans-hierarchical state transitions refined throughout the development.

In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (E-cigs) are marketed as an alternative and replacement domain to the traditional cigarette smoking in many societies for the rescue of smoking cessation. Nevertheless, the vape of E-cigs produce different harmful chemical compounds and carcinogens. The aim of this study is to clarify the histopathological changes that may take place in rat's tongue after exposure to E-cigs and to assess the possible amelioration of such changes after giving up vaping. Methods: Thirty adult male albino rats were divided into three equal groups. Control group: exposed to fresh air for 4 weeks. Exposed group: exposed to smoke vapor of 1ml burnt E-liquid for 1 hour, 5 consecutive days/ week for 4 weeks. Withdrawal group: exposed to the same dose and duration of smoke vapor like group 2 then left without exposure for another 4 weeks. By the end of the experiment, animals were weighted and the tongue was excised and processed for hematoxylin & eosin and Alcian blue/periodic acid Schiff's staining and for proliferating cell nuclear antigen (PCNA) immunohistochemical study. Also, serum malondialdehyde and superoxide dismutase activity were determined. Results: E-cigs exposure hampered the cytoarchitecture of the tongue with loss of some papillae and hyperkeratosis of the others along with increased PCNA immunoreactivity and its area percentage. Also, E-cigs exposure led to redox imbalance. Obviously, stoppage of E-cigs exposure resulted in partial amelioration of histological and biochemical changes. Conclusion: E-cigs vaping produced proliferative changes that impose a metaplasia in the tongue and their withdrawal revealed some degree of improvement. [ABSTRACT FROM AUTHOR]

There is an increased need and focus to understand how local brain microstructure affects the transport of drug molecules directly administered to the brain tissue, for example in convection-enhanced delivery procedures. This study reports a systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fibres, namely the corpus callosum, the fornix and the corona radiata, with the specific aim to map different regions of the tissue and provide essential information for the development of accurate models of brain biomechanics. Ovine samples are imaged using scanning electron microscopy combined with focused ion beam milling to generate 3D volume reconstructions of the tissue at subcellular spatial resolution. Focus is placed on the characteristic cytological feature of the white matter: the axons and their alignment in the tissue. For each tract, a 3D reconstruction of relatively large volumes, including a significant number of axons, is performed and outer axonal ellipticity, outer axonal cross-sectional area and their relative perimeter are measured. The study of well-resolved microstructural features provides useful insight into the fibrous organization of the tissue, whose micromechanical behaviour is that of a composite material presenting elliptical tortuous tubular axonal structures embedded in the extra-cellular matrix. Drug flow can be captured through microstructurally-based models using 3D volumes, either reconstructed directly from images or generated in silico using parameters extracted from the database of images, leading to a workflow to enable physically-accurate simulations of drug delivery to the targeted tissue. Imaging and reconstruction of sheep brain axonal cytoarchitecture provides insight for brain biomechanics models that simulate drug delivery and other biological processes governed by interstitial fluid flow and transport. [ABSTRACT FROM AUTHOR]

Managed honey bees are daily exposed in agricultural settings or wild environments to multiple stressors. Currently, fungicide residues are increasingly present in bees' pollen and nectar and can harm colonies' production and survival. Therefore, our study aimed to evaluate the effects of the fungicide pyraclostrobin on the fat body and pericardial cells of Africanized honey bees. The foragers were divided into three experimental treatment groups and two controls: pyraclostrobin 0.125 ng/µL (FG1), 0.025 ng/µL (FG2), 0.005 ng/µL (FG3), untreated control (CTL), and acetone control (CAC). After five days of oral exposure (ad libitum), the bees were dissected and prepared for histopathological and morphometric analysis. The FG1-treated bees showed extensive cytoarchitecture changes in the fat body and pericardial cells, inducing cell death. Bees from the FG2 group showed disarranged oenocytes, peripheral vacuolization, and pyknotic nuclei of pericardial cells, but the cytoarchitecture was not compromised as observed in FG1. Additionally, immune system cells were observed through the fat body in the FG1 group. Bees exposed to FG3 demonstrated only oenocytes vacuolization. A significant decrease in the oenocyte's surface area for bees exposed to all pyraclostrobin concentrations was observed compared to the CTL and CAC groups. The bees from the FG1 and FG2 treatment groups presented a reduced surface area of pericardial cells compared to the controls and the FG3 group. This study highlighted the harmful effects of fungicide pyraclostrobin concentrations at the individual bee cellular level, potentially harming the colony level on continuous exposure. [ABSTRACT FROM AUTHOR]

The dorsolateral prefrontal cortex (DLPFC) plays a key role in cognitive control and executive functions, including working memory, attention, value encoding, decision making, monitoring, and controlling behavioral strategies. However, the relationships between this variety of functions and the underlying cortical areas, which specifically contribute to these functions, are not yet well-understood. Existing microstructural maps differ in the number, localization, and extent of areas of the DLPFC. Moreover, there is a considerable intersubject variability both in the sulcal pattern and in the microstructure of this region, which impedes comparison with functional neuroimaging studies. The aim of this study was to provide microstructural, cytoarchitectonic maps of the human anterior DLPFC in 3D space. Therefore, we analyzed 10 human post-mortem brains and mapped their borders using a well-established approach based on statistical image analysis. Four new areas (i.e., SFS1, SFS2, MFG1, and MFG2) were identified in serial, cell-body stained brain sections that occupy the anterior superior frontal sulcus and middle frontal gyrus, i.e., a region corresponding to parts of Brodmann areas 9 and 46. Differences between areas in cytoarchitecture were captured using gray level index profiles, reflecting changes in the volume fraction of cell bodies from the surface of the brain to the cortex-white matter border. A hierarchical cluster analysis of these profiles indicated that areas of the anterior DLPFC displayed higher cytoarchitectonic similarity between each other than to areas of the neighboring frontal pole (areas Fp1 and Fp2), Broca's region (areas 44 and 45) of the ventral prefrontal cortex, and posterior DLPFC areas (8d1, 8d2, 8v1, and 8v2). Area-specific, cytoarchitectonic differences were found between the brains of males and females. The individual areas were 3D-reconstructed, and probability maps were created in the MNI Colin27 and ICBM152casym reference spaces to take the variability of areas in stereotaxic space into account. The new maps contribute to Julich-Brain and are publicly available as a resource for studying neuroimaging data, helping to clarify the functional and organizational principles of the human prefrontal cortex. [ABSTRACT FROM AUTHOR]

The inferior frontal sulcus is conceptualized as the landmark delineating ventro-from dorsolateral prefrontal cortex. Functional imaging studies report activations within the sulcus during tasks addressing cognitive control and verbal working memory, while their microstructural correlates are not well defined. Existing microstructural maps, e.g., Brodmann's map, do not distinguish separate areas within the sulcus. We identified six new areas in the inferior frontal sulcus and its junction to the precentral sulcus, ifs1-4, ifj1-ifj2, by combined cytoarchitectonic analysis and receptor autoradiography. A hierarchical cluster analysis of receptor densities of these and neighbouring prefrontal areas revealed that they form a distinct cluster within the prefrontal cortex. Major interhemispheric differences were found in both cyto- and receptorarchitecture. The function of cytoarchitectonically identified areas was explored by comparing probabilistic maps of the areas in stereotaxic space with their functions and co-activation patterns as analysed by means of a coordinate-based meta-analysis. We found a bilateral involvement in working memory, as well as a lateralization of different language-related processes to the left hemisphere, and of music processing and attention to the right-hemispheric areas. Particularly ifj2 might act as a functional hub between the networks. The cytoarchitectonic maps and receptor densities provide a powerful tool to further elucidate the function of these areas. The maps are available through the Human Brain Atlas of the Human Brain Project and serve in combination with the information on the cyto- and receptor architecture of the areas as a resource for brain models and simulations. [ABSTRACT FROM AUTHOR]

Normal functioning of the brain relies on a continual and efficient delivery of energy by a vast network of cerebral blood vessels. The bidirectional coupling between neurons and blood vessels consists of vasodilatory energy demand signals from neurons to blood vessels, and the retrograde flow of energy substrates from the vessels to neurons, which fuel neural firing, growth and other housekeeping activities in the neurons. Recent works indicate that, in addition to the functional coupling observed in the adult brain, the interdependence between the neural and vascular networks begins at the embryonic stage, and continues into subsequent developmental stages. The proposed Vascular Arborization Model (VAM) captures the effect of neural cytoarchitecture and neural activity on vascular arborization. The VAM describes three important stages of vascular tree growth: (i) The prenatal growth phase, where the vascular arborization depends on the cytoarchitecture of neurons and non-neural cells, (ii) the post-natal growth phase during which the further arborization of the vasculature depends on neural activity in addition to neural cytoarchitecture, and (iii) the settling phase, where the fully grown vascular tree repositions its vascular branch points or nodes to ensure minimum path length and wire length. The vasculature growth depicted by VAM captures structural characteristics like vascular volume density, radii, mean distance to proximal neurons in the cortex. VAM-grown vasculature agrees with the experimental observation that the neural densities do not covary with the vascular density along the depth of the cortex but predicts a high correlation between neural areal density and microvascular density when compared over a global scale (across animals and regions). To explore the influence of neural activity on vascular arborization, the VAM was used to grow the vasculature in neonatal rat whisker barrel cortex under two conditions: (i) Control, where the whiskers were intact and (ii) Lesioned, where one row of whiskers was cauterized. The model captures a significant reduction in vascular branch density in lesioned animals compared to control animals, concurring with experimental observation. [ABSTRACT FROM AUTHOR]

The mammalian neocortex has a 6-layered cytoarchitecture, where early- and late-born neurons are positioned deeply and superficially, respectively. Inverted lamination has been observed in mice defective in the Reelin/Disabled-1 (Dab1) pathway. Considering that Dab1 -deficient superficial layer neurons can migrate into the Dab1 +/+ cortical plate and that Dab1 is thought to function cell-autonomously, it is unclear why superficial layer neurons are positioned below deep layer neurons in Reelin / Dab1 -deficient mice. Here, we reconfirmed that Dab1 -/- superficial layer neurons enter the cortical plate using in utero electroporation on embryonic day (E) 14.5 Dab1 -floxed mice. Electroporation in E12.5 Dab1 -floxed mice reconfirmed that many deep layer neurons were mispositioned below the subplate. We also found an accumulation of Dab1 -deficient superficial layer neurons below the cortical plate in many of these brains, in which deep layer neurons below the subplate showed high cell density. These phenotypes were rescued by decreasing the knockout probability and by expressing Dab1 in deep layer neurons. These observations suggest that cell-dense Dab1 -/- deep layer neurons prevent Dab1 -/- superficial layer neurons from entering the cortical plate. This reflects a non-cell-autonomous function of Dab1 and may explain the preplate splitting failure and outside-in lamination observed in Reelin / Dab1 -deficient mice. • Dab1 -/- superficial layer neurons (SLN) enter the Dab1 +/+ cortical plate. • Many Dab1 -/- deep layer neurons (DLN) do not enter the cortical plate. • Cell-dense Dab1 -/- DLNs are impermissible to the migration of Dab1 -/- SLNs. • We interpret this reflects non-cell-autonomous function of Dab1. • Mechanisms of outside-in lamination in Reelin / Dab1 -deficient mice is proposed. [ABSTRACT FROM AUTHOR]

Cats are known to be affected by hippocampal sclerosis, potentially causing antiseizure drug(s) resistance. In order to lay the foundation for a standardized, systematic classification and diagnosis of this pathology in cats, this prospective study aimed at evaluating normal reference values of cellular densities and the cytoarchitecture of the feline hippocampus. Three transverse sections (head, body and tail) of each left hippocampus were obtained from 17 non-epileptic cats of different brachycephalic and mesocephalic breeds and age classes (range: 3–17 years). Histological (hematoxylin and eosin, Nissl) and immunohistochemical (NeuN, GFAP) staining was performed to investigate neuron and astroglial cell populations, as well as the layer thickness of the pyramidal cell layer and granule cell layer. Significant differences in neuronal density (in CA2-CA4 and the granule cell layer) and layer thickness (in CA1-CA3 and the granule cell layer) were evidenced throughout the longitudinal hippocampal axis (p<0.05); on the other hand, the astrocyte density did not differ. Moreover, reference ranges were defined for these parameters in the pyramidal cell layer and in the granule cell layer. The findings did not differ according to breed or age. In veterinary medicine these parameters have not been evaluated in cats so far. As surgical treatment may become a therapeutic option for cats with temporal lobe epilepsy, estimating normal values of the hippocampal cytoarchitecture will help in the standardized histopathological examination of resected hippocampal specimens to reach a diagnosis of hippocampal sclerosis. [ABSTRACT FROM AUTHOR]

Cardiac interstitium is a complex and dynamic environment, vital for normal cardiac structure and function. Telocytes are active cellular players in regulating main events that feature myocardial homeostasis and orchestrating its involvement in heart pathology. Despite the great amount of data suggesting (microscopically, proteomically, genetically, etc.) the implications of telocytes in the different physiological and reparatory/regenerative processes of the heart, understanding their involvement in realizing the heart's mature cytoarchitecture is still at its dawn. Our scrutiny of the recent literature gave clearer insights into the implications of telocytes in the WNT signaling pathway, but also TGFB and PI3K/AKT pathways that, inter alia, conduct cardiomyocytes differentiation, maturation and final integration into heart adult architecture. These data also strengthen evidence for telocytes as promising candidates for cellular therapies in various heart pathologies. [ABSTRACT FROM AUTHOR]

Cetartiodactyls include terrestrial and marine species, all generally endowed with a comparatively lateral position of their eyes and a relatively limited binocular field of vision. To this day, our understanding of the visual system in mammals beyond the few studied animal models remains limited. In the present study, we examined the primary visual cortex of Cetartiodactyls that live on land (sheep, Père David deer, giraffe); in the sea (bottlenose dolphin, Risso's dolphin, long-finned pilot whale, Cuvier's beaked whale, sperm whale and fin whale); or in an amphibious environment (hippopotamus). We also sampled and studied the visual cortex of the horse (a closely related perissodactyl) and two primates (chimpanzee and pig-tailed macaque) for comparison. Our histochemical and immunohistochemical results indicate that the visual cortex of Cetartiodactyls is characterized by a peculiar organization, structure, and complexity of the cortical column. We noted a general lesser lamination compared to simians, with diminished density, and an apparent simplification of the intra- and extra-columnar connections. The presence and distribution of calcium-binding proteins indicated a notable absence of parvalbumin in water species and a strong reduction of layer 4, usually enlarged in the striated cortex, seemingly replaced by a more diffuse distribution in neighboring layers. Consequently, thalamo-cortical inputs are apparently directed to the higher layers of the column. Computer analyses and statistical evaluation of the data confirmed the results and indicated a substantial correlation between eye placement and cortical structure, with a markedly segregated pattern in cetaceans compared to other mammals. Furthermore, cetacean species showed several types of cortical lamination which may reflect differences in function, possibly related to depth of foraging and consequent progressive disappearance of light, and increased importance of echolocation. [ABSTRACT FROM AUTHOR]