The existence of a dopaminergic innervation of the subthalamic nucleus (STN) has been demonstrated in rats but has remained controversial in primates. The aim of the present study was first to demonstrate the existence of a dopaminergic innervation of the STN in monkeys using tracing methods and then to quantify the loss of dopaminergic fibers in the parkinsonian state in monkeys and humans. Following injection of Fluoro-Gold into the STN of a vervet monkey (Cercopithecus aethiops), retrogradely labeled neurons were found to be scattered in all dopaminergic areas of the mesencephalon. Injection of biotin dextran amine into dopaminergic areas A8 and A9 of two monkeys resulted in anterogradely labeled axons located throughout the whole extent of the STN. Labeled axons that also expressed tyrosine hydroxylase (TH) were reconstructed from serial sections. Some terminal axonal arborizations had profuse branching and occupied much of the STN, and others were restricted to small portions of the nucleus. In TH-immunoreactive sections, numerous sparse, fine, and varicose TH-positive fibers were observed in the STN of normal monkeys and humans. Quantification of these TH-positive fibers revealed a 51% loss of TH-positive fibers in MPTP-intoxicated monkeys and a 65% loss in Parkinson's disease patients compared with their respective controls. These findings demonstrate the existence of a dopaminergic innervation of the STN in primates. The loss of dopaminergic innervation in MPTP-intoxicated monkeys and in Parkinson's disease patients may directly affect the activity of STN neurons and could participate in the hyperactivity of the structure.

The morphology and distribution of dopaminergic interplexiform cells were analyzed in 9-day-old rat retinas processed as wholemounts for tyrosine hydroxylase immunohistochemistry. The mean number of dopaminergic interplexiform cells was estimated as about half of the total number of dopaminergic neurons in the immature retina, with a higher density in the temporal retina. Four interplexiform cells were individually analyzed and reconstructed with a computer system. Their arborizations could be divided into three different regions based on both their morphological features and their position within the retinal layers: (1) an internal arborization, spreading at the margin between the inner nuclear layer and the inner plexiform layer, composed of long, thick, somatofugal dendrites branching at acute angles, (2) an external arborization in the middle of the inner nuclear layer, formed by short, thin, varicose, recurved, axon-like processes branching at right angles, (3) and one or more scleral process(es), originating either from the cell body or from the internal arborization, running toward the outermost cell row of the INL, some of which reached the outer plexiform layer. Finally, analysis of the arborization network by computer simulations based on the 4 digitalized cells was compared with a nearest-neighbour analysis of cell body distribution. It showed that cell bodies are almost randomly distributed--at least in the inferior retina--but that an adjustment of dendritic growth and orientation probably occurs to ensure a homogeneous coverage of the retina with a constant degree of overlap in the adult. This report represents the first three-dimensional computer reconstruction of chemically identified neurons in the retina.

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The morphology and distribution of dopaminergic interplexiform cells in adult rat and monkey retinas were analyzed to determine any correlation with the function of dopamine in the outer retinal layers. The retinas were processed as whole mounts for tyrosine hydroxylase immunohistochemistry. There was a network formed by the sclerally directed processes of interplexiform cells in the inner nuclear, outer plexiform, and outer nuclear layers running throughout the retina. Their density was higher in the superior retina than in the inferior retina of the rat and was especially high in the superior temporal quadrant. The external network in this quadrant was significantly less dense in the monkey than in the rat, as are the interplexiform cells. The somata of interplexiform and other dopaminergic cells were about the same size in both rats and monkeys. Computer-assisted reconstruction of external arborizations of individual cells showed that external processes lay very close to horizontal and photoreceptor cells and also to blood capillaries. Because they were long, thin, and highly varicose; branched at right angles; and often arose from an axon hillock, the external processes were identified as axons. Therefore, we define the dopaminergic interplexiform cells as multiaxonal neurons, with at least one outwardly directed axon that reaches the outer plexiform layer. The function of the network of external processes from the interplexiform dopaminergic cells is discussed in terms of modulating the release of dopamine to external layers.

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