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(The FASEB Journal. 2003;17:1820-1830.)
© 2003 FASEB

Electrophysiological and metabolic evidence that high-frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata

CHUN-HWEI TAI*,{dagger}, THOMAS BORAUD*, ERWAN BEZARD*, BERNARD BIOULAC*, CHRISTIAN GROSS* and ABDELHAMID BENAZZOUZ*,1

* Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor Segalen, 33076 Bordeaux Cedex, France; and
{dagger} Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

1Correspondence: Laboratoire de Neurophysiologie, Basal Gang, CNRS UMR 5543, Université Victor Segalen, 146, Rue Léo-Saignat, 33076 Bordeaux Cedex, France. E-mail: Abdelhamid.Benazzouz{at}umr5543.u-bordeaux2.fr

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) has been shown to produce a dramatic alleviation of motor symptoms in patients with advanced Parkinson’s disease. Its functional mechanism, however, remains obscure. We used extracellular recording and in situ cytochrome oxidase (CoI) mRNA hybridization to investigate the effects of HFS of the STN on neuronal activity of the STN and the substantia nigra reticulata (SNr) in normal rats and rats with 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra compacta (SNc). To allow detection of spikes and analysis of firing activity, artifacts recorded during stimulation were scaled down using a template subtraction method. In both normal and lesioned rats, the activity of a majority of STN neurons was inhibited during stimulation. In the SNr, HFS also induced an inhibition of the activity of a majority of neurons in normal and lesioned rats. In situ hybridization histochemistry confirmed these results in that it showed a significant decrease in levels of CoI mRNA expression in the STN and SNr in both normal and lesioned rats during stimulation. These data afford an interesting insight into the functional mechanism of deep brain stimulation and support the hypothesis that HFS exerts an inhibitory influence on STN neuronal firing.—Tai, C.-H., Boraud, T., Bezard, E., Bioulac, B., Gross, C., Benazzouz, A. Electrophysiological and metabolic evidence that high-frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata.


Key Words: Parkinson’s disease • extracellular recordings • basal ganglia • cytochrome oxidase




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