title: Reduced cortical innervation of the subthalamic nucleus in MPTP-treated parkinsonian monkeys.
abstract: The striatum and the subthalamic nucleus are the main entry points for cortical information to the basal ganglia. Parkinson's disease affects not only the function, but also the morphological integrity of some of these inputs and their synaptic targets in the basal ganglia. Significant morphological changes in the cortico-striatal system have already been recognized in patients with Parkinson's disease and in animal models of the disease. To find out whether the primate cortico-subthalamic system is also subject to functionally relevant morphological alterations in parkinsonism, we used a combination of light and electron microscopy anatomical approaches and in vivo electrophysiological methods in monkeys rendered parkinsonian following chronic exposure to low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). At the light microscopic level, the density of vesicular glutamate transporter 1-positive (i.e. cortico-subthalamic) profiles in the dorsolateral part of the subthalamic nucleus (i.e. its sensorimotor territory) was 26.1% lower in MPTP-treated parkinsonian monkeys than in controls. These results were confirmed by electron microscopy studies showing that the number of vesicular glutamate transporter 1-positive terminals and of axon terminals forming asymmetric synapses in the dorsolateral subthalamic nucleus was reduced by 55.1% and 27.9%, respectively, compared with controls. These anatomical findings were in line with in vivo electrophysiology data showing a 60% reduction in the proportion of pallidal neurons that responded to electrical stimulation of the cortico-subthalamic system in parkinsonian monkeys. These findings provide strong evidence for a partial loss of the hyperdirect cortico-subthalamic projection in MPTP-treated parkinsonian monkeys.
authors: 1 Yerkes National Primate Research Centre, Emory University, Atlanta, GA 30329, USA 2 Morris K. Udall Centre of Excellence for Parkinson's Disease Research, Emory University, Atlanta, GA 30329, USA.
authors: Abraham
authors: A
authors: Mathai
authors: 1 Yerkes National Primate Research Centre, Emory University, Atlanta, GA 30329, USA 2 Morris K. Udall Centre of Excellence for Parkinson's Disease Research, Emory University, Atlanta, GA 30329, USA.
authors: Yuxian
authors: Y
authors: Ma
authors: 1 Yerkes National Primate Research Centre, Emory University, Atlanta, GA 30329, USA 2 Morris K. Udall Centre of Excellence for Parkinson's Disease Research, Emory University, Atlanta, GA 30329, USA.
authors: Jean-Francois
authors: JF
authors: Paré
authors: 1 Yerkes National Primate Research Centre, Emory University, Atlanta, GA 30329, USA 2 Morris K. Udall Centre of Excellence for Parkinson's Disease Research, Emory University, Atlanta, GA 30329, USA.
authors: Rosa M
authors: RM
authors: Villalba
authors: 1 Yerkes National Primate Research Centre, Emory University, Atlanta, GA 30329, USA 2 Morris K. Udall Centre of Excellence for Parkinson's Disease Research, Emory University, Atlanta, GA 30329, USA 3 Department of Neurology, Emory University, Atlanta, GA 30322, USA.
authors: Thomas
authors: T
authors: Wichmann
authors: 1 Yerkes National Primate Research Centre, Emory University, Atlanta, GA 30329, USA 2 Morris K. Udall Centre of Excellence for Parkinson's Disease Research, Emory University, Atlanta, GA 30329, USA 3 Department of Neurology, Emory University, Atlanta, GA 30322, USA ysmit01@emory.edu.
authors: Yoland
authors: Y
authors: Smith
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects / Q000473:pathology*; D000882:Haplorhini; D008253:Macaca mulatta; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000473:pathology*
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: Parkinson’s disease; cortico-subthalamic; hyperdirect; synaptic plasticity; vesicular glutamate transporter