title: Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease.
abstract: Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.
authors: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329;
authors: Arun
authors: A
authors: Singh
authors: Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30329;
authors: Klaus
authors: K
authors: Mewes
authors: Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30329;
authors: Robert E
authors: RE
authors: Gross
authors: Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30329;
authors: Mahlon R
authors: MR
authors: DeLong
authors: Centro Integral de Neurociencias AC, Hospitales de Madrid Puerta del Sur, San Pablo University, Móstoles, 28938 Madrid, Spain; Center for Biomedical Research on Neurodegenerative Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain.
authors: José A
authors: JA
authors: Obeso
authors: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329; Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30329; spapa@emory.edu.
authors: Stella M
authors: SM
authors: Papa
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000200:Action Potentials; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D004298:Dopamine / Q000378:metabolism; D004421:Dystonia / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D020329:Essential Tremor / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine
keywords: Parkinson’s disease; basal ganglia; dopamine; electrophysiology; striatal projection neuron