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The Journal of Neuroscience, August 15, 2002, 22(16):7244-7253

Altered Discharge Pattern of Basal Ganglia Output Neurons in an Animal Model of Idiopathic Dystonia

Manuela Gernert, Mustapha Bennay, Maren Fedrowitz, Jan H. Rehders, and Angelika Richter

Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, 30559 Hannover, Germany

A decreased activity of basal ganglia output neurons is thought to underlie idiopathic dystonias and other hyperkinetic movement disorders. We found recently a reduced spontaneous discharge rate of entopeduncular neurons (internal globus pallidus in primates) in dt^sz hamsters, an unique model for idiopathic paroxysmal dystonia in which stress-inducible attacks show an age-dependent severity. Otherwise, it has been suggested that an altered discharge pattern may be more important for the occurrence of dystonia than a reduced discharge rate. Based on qualitative and computerized quantitative evaluations of interspike interval histograms and spike trains of extracellularly recorded single neurons, we investigated the spontaneous discharge pattern of GABAergic entopeduncular and nigral neurons in dt^sz hamsters at different ages. The discharge pattern of entopeduncular neurons was highly irregular and showed an altered burst-like firing in dt^sz hamsters at the age of the most marked expression of dystonia when compared with age-matched nondystonic controls. In line with a recently reported normalization of discharge rates after age-dependent disappearance of dystonia, we found an almost complete normalization of the discharge pattern of entopeduncular neurons after remission of dystonia in dt^sz hamsters. Investigations of GABAergic nigral neurons, reported recently to have the same spontaneous discharge rates in dystonic and nondystonic hamsters, did not show an altered firing pattern in dt^sz hamsters. The present data clearly indicate the fundamental importance of an altered discharge pattern of entopeduncular neurons for the expression of paroxysmal dystonia, and probably also for other dyskinesias, and may explain the improvements obtained by pallidotomy in dystonic patients despite an obviously reduced pallidal output.

Key words: basal ganglia; dt^szhamster; movement disorders; entopeduncular nucleus; globus pallidus; substantia nigra pars reticulata; single-unit recordings; firing pattern

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22167244-10$05.00/0

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