Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine‐beta‐hydroxylase

Abstract

The organization of the cortical monoamine systems, dopamine (DA), and noradrenaline (NA), which have been studied extensively in the rat and more recently in the monkey, had not yet been investigated directly in the human brain. We report here the first systematic account of the regional and laminar distributions of the catecholamine fibers in the human cerebral cortex, using immunohistochemistry of the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH) in 13 cytoarchitectonic areas (4, 6, 9, 3b, 5, 40, 17, 18, 23, 24, 29, insula, and hippocampus) sampled postmortem. The noradrenergic (NA) innervation, mapped with DBH-immunoreactivity (DBH-IR), displayed a characteristic density gradient in the neocortex (highest in the primary sensorimotor areas, decreasing rostrally and caudally) that contrasted with the more uniform density in the limbic cortices (24, 23, 29, insula, hippocampus). NA axons were present in all cortical layers and were least numerous in layer I. The DBH-IR fibers were only partly TH-immunostained (10-50%, on double-labeled sections), suggesting a heterogeneity of the cortical NA axons. The putative dopaminergic (DA) fibers were identified by comparing alternate or double-immunolabeled (DBH-TH) sections, as the TH-IR fibers which contain no DBH-IR. A DA-like innervation was present in all cortical areas, with major regional differences in density and laminar distribution, which closely paralleled cytoarchitectural buildups: 1) the DA-like innervation was densest in the agranular areas, primary and secondary motor areas, anterior cingulate, and insula; it distributed throughout layers I-VI; 2) density was lower in the granular cortices, areas 9 (prefrontal cortex), 23, 3b, 5, 40, and 18, displaying a bilaminar pattern in layers I and V-VI. In all areas, DA-like fibers were most abundant in the molecular layer, with a predominant distribution in its deepest part. Convoluted and coily fibers represented a unique morphologic aspect of the CA innervation in the human cortex. These findings are in agreement with findings in nonhuman primates and demonstrate major evolutionary changes in the organization of the cortical aminergic input as compared with rodents. The most striking features are the expansion of the DA innervation to the whole cortex and the peak of highest density in the motor areas. The regional differentiation of NA innervation is also accentuated. Slight differences were found in the laminar distributions of the amines in humans and primates. These data seem quite promising and open new research fields in neurologic and psychiatric diseases.

Serotonin and Dopamine Transporter Availabilities Correlate with the Loudness Dependence of Auditory Evoked Potentials in Patients with Obsessive-Compulsive Disorder

“…These data point at dopaminergic influences on cortical processing of sensory stimuli. Due to the low dopaminergic innervation of sensory cortices (Lewis et al, 1987;Gaspar et al, 1989;Berger et al, 1991), these effects are supposed to be rather indirect (Juckel et al, 1997). Accordingly, in our study, only the tangential dipoles, representing the activity of a brain region with a dense serotonergic innervation, showed clear and significant correlations with the b-CIT binding and not the radial dipoles, which are associated with the activity of secondary auditory cortices without substantial serotonergic activity.…”

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

“…Seymour Kety was the first to suggest, however, that subtle changes in connectivity could occur in the absence of any discernible biochemical alterations (Kety 1959). To determine whether such a defect is present in schizophrenia, it is now possible to visualize dopamine fibers using antibodies against TH (Lewis et al 1987;Gaspar et al 1989;Noack and Lewis 1989;Samson et al 1990;Williams and Goldman-Rakic 1993).…”

Developing a Neuronal Model for the Pathophysiology of Schizophrenia Based on the Nature of Electrophysiological Actions of Dopamine in the Prefrontal Cortex

“…The significantly sparser, but extensively collateralized, dopamine innervation to the superficial layer I-III of the rodent PFC originates in the A9 medial substantial nigra and the lateral A10 regions (Descarries et al 1987;van Eden et al 1987;Berger et al 1991). On the other hand, the primate and human PFC receive dense bilaminar dopamine inputs: one to the deep layers V-VI, and the other to the superficial layers I-II, with the middle layer III receiving comparatively sparse dopamine innervation (Gaspar et al 1989;Berger et al 1991;Lewis et al 1992;Smiley et al 1992;Williams and Goldman-Rakic 1993;Krimer et al 1997). Thus, in all species, the deep layers V-VI receive dense dopamine innervation, but the density of dopamine innervation in the superficial layers I-III varies across species.…”

“…This dopamine input provides a much more expanded area of innervation in primate and human cortices, encompassing a widespread area of the sensorimotor and association cortices. In primate and human brain, a substantial amount of tyrosine hydroxylase-or dopamine-immunoreactive fibers are found in the motor, premotor, supplementary motor area, parietal, temporal, and posterior cingulate cortices (sensorimotor), in addition to prefrontal, anterior cingulate, insular, piriform, perirhinal, and entorhinal cortices (association) (Berger et al 1988;Gaspar et al 1989;Smiley and Goldman-Rakic 1993).Within the individual cortical layers in the PFC, the mesocortical inputs exhibit a distinctly different pattern in rodent vs. primate and human. In the rodent PFC, afferents from the VTA region (A10) provide dense dopamine input to the deep layers V-VI.…”