Multiple Transmitter Receptors in Regions and Layers of the Human Cerebral Cortex

Abstract

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).Highlights Densities of transmitter receptors vary between areas of human cerebral cortex.Multi-receptor fingerprints segregate cortical layers.The densities of all examined receptor types together reach highest values in the supragranular stratum of all areas.The lowest values are found in the infragranular stratum.Multi-receptor fingerprints of entire areas and their layers segregate functional systemsCortical types (primary sensory, motor, multimodal association) differ in their receptor fingerprints.

Different FDG‐PET metabolic patterns of anti‐AMPAR and anti‐NMDAR encephalitis: Case report and literature review

“…Protein density map modified from Zilles's receptor map. Zilles et al published the cytoarchitecture features of brain regions in 2017 (Zilles & Palomero‐Gallagher, ). They stated that the amount and layer difference of each transmitter receptor defined regions of the brain.…”

“…Map at the protein level was modified from Zilles's protein density map of transmitter receptors, in which the regional protein concentration of multiple transmitter receptors was determined based on postmortem human brain (Palomero‐Gallagher, Amunts, & Zilles, ). To visualize the distribution and intensity of individual receptors, the regional mean densities of all cortical layers from the supplementary materials of the paper by Zilles and Palomero‐Gallagher () were projected on a spatial brain atlas based on Brodmann areas. Several cytoarchitectural regions had no direct equation to the areas on Brodmann's cortical map.…”

“…Multimodal association areas have wide connections to other brain areas and own their specific cytoarchitecture fingerprints that can separate areas and identify their hierarchical position (Zilles & Palomero-Gallagher, 2017). Hypometabolism in association cortices has been reported as a frequent FDG-PET finding in patients with autoimmune encephalitic (Baumgartner et al, 2013).…”

Interlaminar Glia and Other Glial Themes Revisited: Pending Answers Following Three Decades of Glial Research

“…In particular, for example, some recent studies on the comparative distribution of neurotransmitter receptors in the brains of humans and extant primate species were reported by Zilles and colleagues [13,14], as well as comparative genetic studies by Pu et al [15], Muntané et al [16] and Mitchell and Silver [17]. Yet, the ethical limitations on the experimental use of primate species, and the needed minimization of invasive actions to be taken on them, as well as added limitations imposed on the inclusion in experimental protocols of extant species of great apes-mostly those genetically closer as Pan troglodytes and Pan paniscus (chimpanzee and bonobo, respectively)-calls for developing imaginative and minimally invasive research tools and procedures.…”

Ultrastructural heterogeneity of human layer 4 excitatory synaptic boutons in the adult temporal lobe neocortex

“…47The human TLN representing ~17% of the total volume of the neocortex (Kiernan 2012) is regarded as 48 a highly specialized associative brain region roughly subdivided into a superior, medial and inferior gyrus 49 that is highly interconnected with the limbic and various sensory systems. In addition, it is well documented 50 that the TLN represents a homotypic granular, six-layered associative neocortex comparable in its 51 cytoarchitecture with primary sensory cortices but different to heterotypic agranular motor cortex (von 52 Economo and Koskinas 1925;Vogt 2009;Zilles et al 2015, Zilles andPalomero-Gallagher 2017).The 53 growing interest in the TLN is motivated by its importance in high-order brain functions as audition, vision, 54 memory, language processing, and various multimodal associations. Moreover, the temporal lobe is also 55 involved in several neurological diseases most importantly as the area of origin and onset of temporal lobe 56 epilepsy (TLE; reviewed by Allone et al 2017;Tai et al 2018).…”