Role of external pallidal segment in primate parkinsonism: comparison of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism and lesions of the external pallidal segment.
These experiments re-examined the notion that reduced activity in the external pallidal segment (GPe) results in the abnormalities of neuronal discharge in the subthalamic nucleus (STN) and the internal pallidal segment (GPi) and in the development of parkinsonian motor signs. Extracellular recording in two rhesus monkeys, which had been rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed that the average neuronal discharge rate decreased in GPe but increased in STN and GPi. After MPTP, neurons in all three nuclei tended to discharge in oscillatory bursts. In addition, GABA release in STN (measured with microdialysis) was reduced, indicative of reduced activity along the GPe-STN pathway. Finally, the concentration of glutamic acid dehydrogenase (GAD; measured with autoimmunoradiography) was increased in GPe and GPi, likely reflecting increased striatal input and increased activity of local axon collaterals, respectively. Surprisingly, GAD protein in STN remained unchanged, indicating that the usual assumption that GAD levels are determined primarily by the overall activity of GABAergic elements may be too simplistic. The results from the MPTP-treated animals were compared with results obtained in a second group of three animals with ibotenic acid lesions of GPe. GPe lesions resulted in increased discharge in STN and GPi, comparable with the changes seen after MPTP but did not induce oscillatory bursting and had no behavioral effects. The results indicate that a mere reduction of GPe activity does not produce parkinsonism. Other changes, such as altered discharge patterns in STN and GPi, may play an important role in the generation of parkinsonism.
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Jesus
J
Soares
Michele A
MA
Kliem
Ranjita
R
Betarbet
J Timothy
JT
Greenamyre
Bryan
B
Yamamoto
Thomas
T
Wichmann
D000200:Action Potentials; D000818:Animals; D001479:Basal Ganglia / Q000737:chemistry / Q000473:pathology; D001522:Behavior, Animal; D005917:Globus Pallidus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020267:MPTP Poisoning / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008253:Macaca mulatta; D017551:Microdialysis; D009474:Neurons / Q000502:physiology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000378:metabolism / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors