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The Journal of Neuroscience, September 5, 2007, 27(36):9595-9606; doi:10.1523/JNEUROSCI.2583-07.2007

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Neurobiology of Disease
Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats

Pauline Belujon, Erwan Bezard, Anne Taupignon, Bernard Bioulac, and Abdelhamid Benazzouz

Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5227, Université Victor Segalen, 33076 Bordeaux Cedex, France

Correspondence should be addressed to Dr. Abdelhamid Benazzouz, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5227, Université Victor Segalen, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France. Email: Abdelhamid.Benazzouz{at}u-bordeaux2.fr

The subthalamic nucleus (STN) plays a key role in the pathophysiology of Parkinson's disease. The modulation of the STN by norepinephrine, however, is unknown. The present study aims at characterizing the effects of systemic administration of noradrenergic agents on locomotor activity and on in vivo extracellularly recorded STN neuronal activity in intact and 6-hydroxydopamine (6-OHDA)-lesioned rats. Using selective agonists and antagonists of {alpha}1 and {alpha}2 adrenergic receptors (ARs), we show that STN neurons have functional {alpha}1- and {alpha}2-AR controlling STN firing with an impact on locomotor activity. We further demonstrate that those systemic effects are supported, at least in part, by a direct modulation of STN neuronal activity, using patch-clamp recordings of STN neurons in brain slices. These findings support the premise that hypokinesia is associated with an increased STN neuronal activity, and that improvements of parkinsonian motor abnormalities are associated with a decrease in STN activity. Our data challenge assumptions about the role of {alpha}1-AR and {alpha}2-AR in the regulation of STN neurons in both intact and 6-OHDA-lesioned rats and further ground the rationale for using {alpha}2-AR noradrenergic antagonists in Parkinson's disease, albeit via an unexpected mechanism.

Key words: norepinephrine (noradrenergic); subthalamic nucleus; Parkinson's disease; locomotor activity; extracellular recordings; 6-hydroxydopamine

Received Dec. 22, 2006; revised June 7, 2007; accepted July 7, 2007.

Correspondence should be addressed to Dr. Abdelhamid Benazzouz, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5227, Université Victor Segalen, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France. Email: Abdelhamid.Benazzouz{at}u-bordeaux2.fr






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