Dopaminergic innervation of the subthalamic nucleus in the normal state, in MPTP-treated monkeys, and in Parkinson's disease patients

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 d opaminergic innervation of the STN in monkeys using tracing methods and the n 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 ve rvet monkey (Cercopithecus aethiops), retrogradely labeled neurons were fou nd to be scattered in all dopaminergic areas of the mesencephalon. Injectio n 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) we re reconstructed from serial sections. Some terminal axonal arborizations h ad profuse branching and occupied much of the STN, and others were restrict ed to small portions of the nucleus. In TH-immunoreactive sections, numerou s sparse, fine, and varicose TH-positive fibers were observed in the STN of normal monkeys and humans. Quantification of these TH-positive fibers reve aled a 51% loss of TH-positive fibers in MPTP-intoxicated monkeys and a 65% loss in Parkinson's disease patients compared with their respective contro ls. These findings demonstrate the existence of a dopaminergic innervation of the STN in primates. The loss of dopaminergic innervation in MPTP-intoxi cated monkeys and in Parkinson's disease patients may directly affect the a ctivity of STN neurons and could participate in the hyperactivity of the st ructure. J. Comp. Neurol. 425:121-129, 2000. (C) 2000 Wiley-Liss, Inc.