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

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 M(2) and nicotinic α(4)β(2) receptor densities, and to a lesser degree also by noradrenergic α(2) and serotonergic 5-HT(2) 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 systems. Cortical types (primary sensory, motor, multimodal association) differ in their receptor fingerprints.