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.

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DARPP-32, a dopamine (DA) and cAMP-regulated phosphoprotein, is associated with dopaminoceptive neurons bearing D-1 receptors in the basal ganglia. The present study addressed the distribution of DARPP-32 in the primate cerebral cortex and its putative association with D-1 receptor laden cells in this structure. DARPP-32-like immunoreactive (LIR) neurons were examined in the cerebral cortex of 3-day-old (P3), 6-week-old (P42), and adult rhesus monkeys. In the younger cases, a large number of DARPP-32 positive neurons, with the morphological characteristics of pyramidal cells, were observed throughout the cortex, in layers V-VI, and to a lesser extent in layer II and uppermost layer III. In the parietal, insular, temporal, and occipital cortices, DARPP-32 positive neurons were arranged in a monolayer in layer Va. They were often clustered in small groups with a bundling of their dendrites. In the primary motor cortex, Betz cells were among the labeled population. In the association and somatosensory areas, the basal dendrites of DARPP-32 positive neurons and the prominent tufting of their apical dendrites in layer I contributed to an essential bilaminar pattern resembling the distribution reported for DA afferents and D-1 receptors in these areas. The prominence and widespread distribution of DARPP-32 positive neurons in layer V may be a specialization of primate cortex since such cells are found only in restricted locations in rodents. The literature on the connections of the cerebral cortex suggests that a large number of the DARPP-32 positive neurons in layer VI and perhaps even in layer Va may be corticothalamic neurons. An important developmental observation was the presence of DARPP-32-LIR neurons in the white matter. They were prominent in the neonates but could not be seen in the adult. Their location as well as their type and shape were reminiscent of interstitial neurons. In the adult monkeys, the distribution of DARPP-32-LIR neurons was more circumscribed: they were numerous in the ventral temporal gyrus and in areas related to the limbic system: caudal orbitofrontal cortex, insula, temporal pole, entorhinal, and anterior cingulate cortex. Weak labeling was detected in layer Va of the superior temporal and parietal cortex, in some prefrontal areas (10, 13, and medial 9), and in the premotor and supplementary motor cortex; in adults, unlike neonates, few DARPP-32-LIR neurons were present in the dorsolateral prefrontal cortex, the primary motor or the primary visual or prestriate cortices.(ABSTRACT TRUNCATED AT 400 WORDS)