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Dynamics and functions of neural circuits depend on interactions mediated by receptors. Therefore, a comprehensive map of receptor organization across cortical regions is needed. In this study, we used in vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrated the receptor data with anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of receptor expression per neuron. This aligns with the cortical hierarchy from sensory cortex to higher cognitive areas. A second gradient, driven by serotonin 5-HT 1A receptors, peaks in the anterior cingulate, default mode and salience networks. We found a similar pattern of 5-HT 1A expression in the human brain. Thus, the macaque may be a promising translational model of serotonergic processing and disorders. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration in higher cognitive areas., (© 2023. The Author(s).)

Transmitter receptors constitute a key component of the molecular machinery for intercellular communication in the brain. Recent efforts have mapped the density of diverse transmitter receptors across the human cerebral cortex with an unprecedented level of detail. Here, we distill these observations into key organizational principles. We demonstrate that receptor densities form a natural axis in the human cerebral cortex, reflecting decreases in differentiation at the level of laminar organization and a sensory-to-association axis at the functional level. Along this natural axis, key organizational principles are discerned: progressive molecular diversity (increase of the diversity of receptor density); excitation/inhibition (increase of the ratio of excitatory-to-inhibitory receptor density); and mirrored, orderly changes of the density of ionotropic and metabotropic receptors. The uncovered natural axis formed by the distribution of receptors aligns with the axis that is formed by other dimensions of cortical organization, such as the myelo- and cytoarchitectonic levels. Therefore, the uncovered natural axis constitutes a unifying organizational feature linking multiple dimensions of the cerebral cortex, thus bringing order to the heterogeneity of cortical organization., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V, and VI. In contrast, motor-frontal cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness from motor to frontal association cortices. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness, and, ultimately, functional neuroanatomy., Competing Interests: The authors have declared that no competing interests exist.

Cortical layers have classically been identified by their distinctive and prevailing cell types and sizes, as well as the packing densities of cell bodies or myelinated fibers. The densities of multiple receptors for classical neurotransmitters also vary across the depth of the cortical ribbon, and thus determine the neurochemical properties of cyto- and myeloarchitectonic layers. However, a systematic comparison of the correlations between these histologically definable layers and the laminar distribution of transmitter receptors is currently lacking. We here analyze the densities of 17 different receptors of various transmitter systems in the layers of eight cytoarchitectonically identified, functionally (motor, sensory, multimodal) and hierarchically (primary and secondary sensory, association) distinct areas of the human cerebral cortex. Maxima of receptor densities are found in different layers when comparing different cortical regions, i.e. laminar receptor densities demonstrate differences in receptorarchitecture between isocortical areas, notably between motor and primary sensory cortices, specifically the primary visual and somatosensory cortices, as well as between allocortical and isocortical areas. Moreover, considerable differences are found between cytoarchitectonical and receptor architectonical laminar patterns. Whereas the borders of cyto- and myeloarchitectonic layers are well comparable, the laminar profiles of receptor densities rarely coincide with the histologically defined borders of layers. Instead, highest densities of most receptors are found where the synaptic density is maximal, i.e. in the supragranular layers, particularly in layers II-III. The entorhinal cortex as an example of the allocortex shows a peculiar laminar organization, which largely deviates from that of all the other cortical areas analyzed here., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

How does cortical tissue change as brain function and behavior improve from childhood to adulthood? By combining quantitative and functional magnetic resonance imaging in children and adults, we find differential development of high-level visual areas that are involved in face and place recognition. Development of face-selective regions, but not place-selective regions, is dominated by microstructural proliferation. This tissue development is correlated with specific increases in functional selectivity to faces, as well as improvements in face recognition, and ultimately leads to differentiated tissue properties between face- and place-selective regions in adulthood, which we validate with postmortem cytoarchitectonic measurements. These data suggest a new model by which emergent brain function and behavior result from cortical tissue proliferation rather than from pruning exclusively., (Copyright © 2017, American Association for the Advancement of Science.)

Human subgenual anterior cingulate cortex (sACC) is involved in affective experiences and fear processing. Functional neuroimaging studies view it as a homogeneous cortical entity. However, sACC comprises several distinct cyto- and receptorarchitectonical areas: 25, s24, s32, and the ventral portion of area 33. Thus, we hypothesized that the areas may also be connectionally and functionally distinct. We performed structural post mortem and functional in vivo analyses. We computed probabilistic maps of each area based on cytoarchitectonical analysis of ten post mortem brains. Maps, publicly available via the JuBrain atlas and the Anatomy Toolbox, were used to define seed regions of task-dependent functional connectivity profiles and quantitative functional decoding. sACC areas presented distinct co-activation patterns within widespread networks encompassing cortical and subcortical regions. They shared common functional domains related to emotion, perception and cognition. A more specific analysis of these domains revealed an association of s24 with sadness, and of s32 with fear processing. Both areas were activated during taste evaluation, and co-activated with the amygdala, a key node of the affective network. s32 co-activated with areas of the executive control network, and was associated with tasks probing cognition in which stimuli did not have an emotional component. Area 33 was activated by painful stimuli, and co-activated with areas of the sensorimotor network. These results support the concept of a connectional and functional specificity of the cyto- and receptorarchitectonically defined areas within the sACC, which can no longer be seen as a structurally and functionally homogeneous brain region., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-unconstrained but not task-constrained connectivity. We thus identified distinct regions in the PMC and characterized their neural networks and functional implications., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Human area 32 plays crucial roles in emotion and memory consolidation. It has subgenual (s32), pregenual (p32), dorsal, and midcingulate components. We seek to determine whether macaque area 32 has subgenual and pregenual subdivisions and the extent to which they are comparable to those in humans by means of NeuN immunohistochemistry and multireceptor analysis of laminar profiles. The macaque has areas s32 and p32. In s32, layer IIIa/b neurons are larger than those of layer IIIc. This relationship is reversed in p32. Layer Va is thicker and Vb thinner in s32. Area p32 contains higher kainate, benzodiazepine (BZ), and serotonin (5-HT)1A but lower N-methyl-D-aspartate (NMDA) and α2 receptor densities. Most differences were found in layers I, II, and VI. Together, these differences support the dual nature of macaque area 32. Comparative analysis of human and macaque s32 and p32 supports equivalences in cyto- and receptor architecture. Although there are differences in mean areal receptor densities, there are considerable similarities at the layer level. Laminar receptor distribution patterns in each area are comparable in the two species in layers III-Va for kainate, NMDA, γ-aminobutyric acid (GABA)B , BZ, and 5-HT1A receptors. Multivariate statistical analysis of laminar receptor densities revealed that human s32 is more similar to macaque s32 and p32 than to human p32. Thus, macaque 32 is more complex than hitherto known. Our data suggest a homologous neural architecture in anterior cingulate s32 and p32 in human and macaque brains., (© 2013 Wiley Periodicals, Inc.)

Cortical folding is a hallmark of many, but not all, mammalian brains. The degree of folding increases with brain size across mammals, but at different scales between orders and families. In this review we summarize recent studies that have shed light on cortical folding and discuss new models that arise from these data. Genetic analyses argue for an independent development of brain volume and gyrification, but more recent data on the cellular development of the cortex and its connectivity highlight the role of these processes in cortical folding (grey matter hypothesis). This, and the widely discussed tension hypothesis, further tested by analyzing the mechanical properties of maturing nerve fibers, synapses, and dendrites, can provide the basis for a future integrative view on cortical folding., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: Cell culture studies and animal models point to an important role of oxidative/nitrosative stress in the pathogenesis of cerebral ammonia toxicity. However, it is unknown whether oxidative/nitrosative stress in the brain is also characteristic of hepatic encephalopathy (HE) in humans. We therefore analyzed post mortem cortical brain tissue samples from patients with cirrhosis dying with or without HE in comparison with brains from patients without liver disease. Significantly elevated levels of protein tyrosine-nitrated proteins, heat shock protein-27, and 8-hydroxyguanosine as a marker for RNA oxidation were found in the cerebral cortex of HE patients, but not of patients with cirrhosis but without HE. Glutamine synthetase (GS) activity was significantly decreased, whereas GS protein expression was not significantly affected. Protein expression of the glutamate/aspartate cotransporter was up-regulated in HE, whereas protein expression of neuronal and inducible nitric oxide synthases, manganese-dependent and copper/zinc-dependent superoxide dismutase, and glial glutamate transporter-1 were not significantly increased., Conclusion: These data indicate that HE in patients with cirrhosis is associated with oxidative/nitrosative stress, protein tyrosine nitration, and RNA oxidation, suggesting a role of oxidative stress in the pathogenesis of HE in patients with cirrhosis.

The concentration of transmitter receptors varies between different locations in the human cerebral cortex, but also between the different cortical layers within the same area. Analyzing the regional differences in the laminar distribution patterns of various neurotransmitter receptor binding sites by means of quantitative receptor autoradiography may thus provide a functionally relevant insight into the organization of the cortex. Here we introduce an approach to the analysis of in vitro receptor autoradiographic data, providing a framework for the assessment of differences in both mean concentration and laminar distribution patterns across multiple subjects. Initially, laminar receptor distribution patterns for cortical areas are quantified by sampling density profiles in a series of regions of interest (ROIs) from digitalized autoradiographs and computing a mean profile per ROI. These ROI mean profiles are then corrected for distortions in the laminar pattern introduced by cortical folding and averaged to yield a mean profile per area, receptor and hemisphere. Differences in mean binding site concentration between areas are quantified by the asymmetry coefficient which is the difference of the mean concentrations divided by their sum. To quantify differences in laminar receptor distribution patterns between areas, the effects of absolute binding site concentration are first removed by dividing each profile by its mean value. Differences in the laminar pattern were then quantified by calculating the Euclidean distance between these mean corrected profiles. For single subject analysis, we propose a permutation test, comparing the differences between the mean profiles for two areas to differences between groups of profiles randomly assembled from all ROIs sampled in either area. Group inference can then be based on a between-subject conjunction analysis after correcting p-values to control for multiple comparisons. The feasibility of the presented approach is demonstrated by an exemplary analysis of the neurochemical differences between the ventral parts of the second and the third visual area.

Three-dimensional maximum probability maps (MPMs) of cytoarchitectonically defined cortical regions based on postmortem histological studies have recently been made available in the stereotaxic reference space of the Montreal Neurological Institute (MNI) single subject template. This permits the use of cytoarchitectonic maps for the analysis of functional in vivo datasets, including neuroreceptor positron emission tomography (PET) studies. In this feasibility study, we used 5-hydroxytryptamine 2A (5-HT2A) receptor PET to test the applicability of maximum cytoarchitectonic probability maps for quantitative analysis. As the outcome parameter, we extracted local distribution volume ratios (DVRs) from 19 cytoarchitectonically defined volumes of interest (VOIs) per hemisphere from five healthy subjects. The experimental design included a forward ('PET to atlas' normalization) and a backward ('atlas to PET' normalization) procedure to double-check the stability of transformation and overlay. Resulting DVRs were compared with receptor densities (RDs) obtained from postmortem [3H]ketanserin autoradiography of multiple areas. Correlations between the bi-directional normalization procedures (r = 0.89; 38 VOIs) as well as between in vivo and vitro data (nine VOIs; r = 0.64 and r = 0.47 for forward and backward procedure, respectively) suggest that the implementation of cytoarchitectonic maximum probability maps is a promising method for an accurate and observer-independent analysis of neuroreceptor PET data.

The currently available architectonic maps of the human cerebral cortex do not match the high degree of cortical segregation as shown by functional imaging. Such functional imaging studies have demonstrated a considerable number of functionally specialized areas not displayed in the architectonic maps. We therefore analysed the regional and laminar distribution of various transmitter receptors in the human cerebral cortex, because these signalling molecules play a crucial role in cortical functions. They may provide a novel and functionally more relevant insight into the regional organization of the cortex, which cannot be achieved by architectonic observations in cell body- or myelin-stained sections. Serial cryostat sections through whole human hemispheres were used for quantitative receptor autoradiography. The regional and laminar densities of numerous receptors of classic transmitter systems were analysed. Alternating sections were stained for comparisons based on cyto- or myeloarchitectonic criteria. Our results demonstrate that the regional distribution of transmitter receptors reflects well-established cyto- and myeloarchitectonically defined borders of cortical areas, but in addition enables the identification of more cortical areas than previously demonstrated. Moreover, the laminar distribution patterns of a given receptor type in different cortical areas as well as those of different receptor types in the same cortical area reveal novel and functionally relevant data concerning the intracortical organization in the human cerebral cortex.

8328208 20 Pérez-Santos I, García-Cabezas MÁ, Cavada C. Mapping the primate thalamus: systematic approach to analyze the distribution of subcortical neuromodulatory afferents. The digital era of neuroscience and current open science practices have resulted in the generation and availability of numerous datasets reflecting different aspects of the brain's structural and functional segregation. Neuroanatomical knowledge is a fundamental component of neuroimaging analyses, since it enables researchers to interpret their findings in the context of the underlying cytoarchitectonic, molecular and connectional segregation of the brain. 10.1007/s00429-022-02548-0. 35962240 7 García-Cabezas M, Pérez-Santos I, Cavada C. Mapping the primate thalamus: historical perspective and modern approaches for defining nuclei. [Extracted from the article]

We measured the densities (fmol/mg protein) of 15 different receptors of various transmitter systems in the supragranular, granular and infragranular strata of 44 areas of visual, somatosensory, auditory and multimodal association systems of the human cerebral cortex. Receptor densities were obtained after labeling of the receptors using quantitative in vitro receptor autoradiography in human postmortem brains. The mean density of each receptor type over all cortical layers and of each of the three major strata varies between cortical regions. In a single cortical area, the multi-receptor fingerprints of its strata (i.e., polar plots, each visualizing the densities of multiple different receptor types in supragranular, granular or infragranular layers of the same cortical area) differ in shape and size indicating regional and laminar specific balances between the receptors. Furthermore, the three strata are clearly segregated into well definable clusters by their receptor fingerprints. Fingerprints of different cortical areas systematically vary between functional networks, and with the hierarchical levels within sensory systems. Primary sensory areas are clearly separated from all other cortical areas particularly by their very high muscarinic M2 and nicotinic α4β2 receptor densities, and to a lesser degree also by noradrenergic α2 and serotonergic 5-HT2 receptors. Early visual areas of the dorsal and ventral streams are segregated by their multi-receptor fingerprints. The results are discussed on the background of functional segregation, cortical hierarchies, microstructural types, and the horizontal (layers) and vertical (columns) organization in the cerebral cortex. We conclude that a cortical column is composed of segments, which can be assigned to the cortical strata. The segments differ by their patterns of multi-receptor balances, indicating different layer-specific signal processing mechanisms. Additionally, the differences between the strata-and area-specific fingerprints of the 44 areas reflect the segregation of the cerebral cortex into functionally and topographically definable groups of cortical areas (visual, auditory, somatosensory, limbic, motor), and reveals their hierarchical position (primary and unimodal (early) sensory to higher sensory and finally to multimodal association areas). [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) of glutamatergic or GABAergic measures in anterior cingulate cortex (ACC) was found altered in psychiatric disorders and predictive of interindividual variations of functional responses in healthy populations. Several ACC subre-gions have been parcellated into receptor-architectonically different portions with heterogeneous fingerprints for excitatory and inhib-itory receptors. Similarly, these subregions overlap with functionally distinct regions showing opposed signal changes toward stimulation or resting conditions. We therefore investigated whether receptor-architectonical and functional segregation of the cingulate cortex in humans was also reflected in its local concentrations of glutamate (Glu), glutamine (Gin), and GABA. To accomplish a multiregion estimation of all three metabolites in one robust and reliable session, we used an optimized 7T-stimulated echo-acquisition mode method with variable-rate selective excitation pulses. Our results demonstrated that, ensuring high data retest reliability, four cingulate subregions discerning e.g., pregenual ACC (pgACC) from anterior mid-cingulate cortex showed different metabolite concentrations and ratios reflective of regionally specific inhibition/excitation balance. These findings could be controlled for potential influences of local gray matter variations or MRS voxel-placement deviations. Pregenual ACC was found to have significantly higher GABA and Glu concentrations than other regions. This pattern was not paralleled by Gin concentrations, which for both absolute and relative values showed a rostrocaudal gradient with highest values in pgACC. Increased excitatory Glu and inhibitory GABA in pgACC were shown to follow a regional segregation agreeing with recently shown receptor-architectonic GABAB receptor distribution in ACC, whereas Gin distribution followed a pattern of AMPA receptors. [ABSTRACT FROM AUTHOR]

The avian nidopallium caudolaterale is a multimodal area in the caudal telencephalon that is apparently not homologous to the mammalian prefrontal cortex but serves comparable functions. Here we analyzed binding-site densities of glutamatergic AMPA, NMDA and kainate receptors, GABAergic GABA, muscarinic M, M and nicotinic (nACh) receptors, noradrenergic α and α, serotonergic 5-HT and dopaminergic D-like receptors using quantitative in vitro receptor autoradiography. We compared the receptor architecture of the pigeons' nidopallial structures, in particular the NCL, with cortical areas Fr2 and Cg1 in rats and prefrontal area BA10 in humans. Our results confirmed that the relative ratios of multiple receptor densities across different nidopallial structures (their 'receptor fingerprints') were very similar in shape; however, the absolute binding densities (the 'size' of the fingerprints) differed significantly. This finding enables a delineation of the avian NCL from surrounding structures and a further parcellation into a medial and a lateral part as revealed by differences in densities of nACh, M, kainate, and 5-HT receptors. Comparisons of the NCL with the rat and human frontal structures showed differences in the receptor distribution, particularly of the glutamate receptors, but also revealed highly conserved features like the identical densities of GABA, M, nACh and D-like receptors. Assuming a convergent evolution of avian and mammalian prefrontal areas, our results support the hypothesis that specific neurochemical traits provide the molecular background for higher order processes such as executive functions. The differences in glutamate receptor distributions may reflect species-specific adaptations. [ABSTRACT FROM AUTHOR]

Mapping of multiple receptors of neurotransmitters provides insight into the spatial distribution of neurotransmission-relevant molecules in the cerebral cortex. During development, lack of reelin leads to impaired migration, disturbed lamination of the hippocampus and inverted neocortical layering. In the adult, reelin may regulate synaptic plasticity by modulating neurotransmitter receptor function. Using quantitative in vitro receptor autoradiography, different receptors, in particular, the binding site densities and laminar distribution of various glutamate, GABA, muscarinic and nicotinic acetylcholine, serotonin, dopamine and adenosine receptors, were analyzed in cortical and subcortical structures of reeler and wild-type brains. Differential changes in the laminar distribution, maximum binding capacity ( B) and regional density of neurotransmitter receptors were found in the reeler brain. A decrease of whole brain B was found for adenosine A and GABA receptors. In the forebrain, several binding sites were differentially up- or down-regulated (kainate, A, benzodiazepine, 5-HT, M, α and α). In the hippocampus, a significant decrease of GABA, 5-HT and $$ {\text{A}}_1^{\prime} $$ receptors were observed. The density of M receptors increased, while other receptors remained unchanged. In the neocortex, some receptors demonstrated an obviously inverted laminar distribution (AMPA, kainate, NMDA, GABA, 5-HT, M, M, nAch), while the distribution of others (A, GABA, benzodiazepine, 5-HT, muscarinic M, adrenergic α, α) seemed to be less affected. Thus, the laminar receptor distribution is modulated by the developmental impairment and suggests and reflects partially the laminar inversion in reeler mice. [ABSTRACT FROM AUTHOR]

Combustion-derived nanoparticles, such as diesel engine exhaust particles, have been implicated in the adverse health effects of particulate air pollution. Recent studies suggest that inhaled nanoparticles may also reach and/or affect the brain. The aim of our study was to comparatively evaluate the effects of short-term diesel engine exhaust (DEE) inhalation exposure on rat brain and lung. After 4 or 18 h recovery from a 2 h nose-only exposure to DEE (1.9 mg/m3), the mRNA expressions of heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytochrome P450 1A1 (CYP1A1) were investigated in lung as well as in pituitary gland, hypothalamus, olfactory bulb, olfactory tubercles, cerebral cortex, and cerebellum. HO-1 protein expression in brain was investigated by immunohistochemistry and ELISA. In the lung, 4 h post-exposure, CYP1A1 and iNOS mRNA levels were increased, while 18 h post-exposure HO-1 was increased. In the pituitary at 4 h post-exposure, both CYP1A1 and HO-1 were increased; HO-1 was also elevated in the olfactory tuberculum at this time point. At 18 h post-exposure, increased expression of HO-1 and COX-2 was observed in cerebral cortex and cerebellum, respectively. Induction of HO-1 protein was not observed after DEE exposure. Bronchoalveolar lavage analysis of inflammatory cell influx, TNF-α, and IL-6 indicated that the mRNA expression changes occurred in the absence of lung inflammation. Our study shows that a single, short-term inhalation exposure to DEE triggers region-specific gene expression changes in rat brain to an extent comparable to those observed in the lung. [ABSTRACT FROM AUTHOR]

Abstract: Regional distributions of ligand binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABAA, GABAB; cholinergic: muscarinic M2, nicotinic; adrenergic: α1, α2; serotonergic: 5-HT1A, 5-HT2; dopaminergic: D1) were studied in human postmortem brains by means of quantitative receptor autoradiography. Binding site densities were measured in the superior parietal lobule (SPL) (areas 5L, 5M, 5Ci, and different locations within Brodmann''s area (BA) 7), somatosensory (BA 2), and visual cortical areas (BA 17, and different locations within BAs 18 and 19). Similarities of receptor distribution between cortical areas were analyzed by cluster analysis, uni- and multivariate statistics of mean receptor densities (averaged over all cortical layers), and profiles representing the laminar distribution patterns of receptors. A considerable heterogeneity of regional receptor densities and laminar patterns between the sites was found in the SPL and the visual cortex. The most prominent regional differences were found for M2 receptors. In the SPL, rostrocaudally oriented changes of receptor densities were more pronounced than those in mediolateral direction. The receptor distribution in the rostral SPL was more similar to that of the somatosensory cortex, whereas caudal SPL resembled the receptor patterns of the dorsolateral extrastriate visual areas. These results suggest a segregation of the different SPL areas based on receptor distribution features typical for somatosensory or visual areas, which fits to the dual functional role of this cortical region, i.e., the involvement of the human SPL in visuomotor and somatosensory motor transformations. [Copyright &y& Elsevier]

The somatosensory cortex is a brain region responsible for receiving and processing sensory information from across the body and is structurally and functionally heterogeneous. Since the chemoarchitectonic segregation of the cerebral cortex can be revealed by transmitter receptor distribution patterns, by using a quantitative multireceptor architectonical analysis, we determined the number and extent of distinct areas of the macaque somatosensory cortex. We identified three architectonically distinct cortical entities within the primary somatosensory cortex (i.e., 3bm, 3bli, 3ble), four within the anterior parietal cortex (i.e., 3am, 3al, 1 and 2) and six subdivisions (i.e., S2l, S2m, PVl, PVm, PRl and PRm) within the lateral fissure. We provide an ultra-high resolution 3D atlas of macaque somatosensory areas in stereotaxic space, which integrates cyto- and receptor architectonic features of identified areas. Multivariate analyses of the receptor fingerprints revealed four clusters of identified areas based on the degree of (dis)similarity of their receptor architecture. Each of these clusters can be associated with distinct levels of somatosensory processing, further demonstrating that the functional segregation of cortical areas is underpinned by differences in their molecular organization. • Cyto-, myelo- and receptor-based mapping of macaque somatosensory cortex. • Medial-lateral segregation exists in the receptor architectures of areas 3a and 3b. • Novel subdivisions were identified within the macaque SII complex. • Cluster analysis unveiled the hierarchical processing within somatosensory cortex. [ABSTRACT FROM AUTHOR]