Noradrenergic control of the subthalamic nucleus
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1
Univ. Bordeaux, Neurodegenerative Diseseases Institute/CNRS UMR 5293, France
The subthalamic nucleus (STN) plays a key role in the pathophysiology of Parkinson’s disease. This was demonstrated by the fact that STN neurons express more bursts in animal models of the disease and by the ability of STN inactivation to alleviate motor deficits. However, the origin of the bursts and the causal link between STN bursts and motor deficits remain unknown. The present study aimed to investigate the role of noradrenergic receptor modulation on the firing activity of STN neurons and the impact of this modulation on locomotor activity in sham and 6-hydroxydopamine-lesioned rats. Using selective agonists and antagonists of α1- and α2-adrenergic receptors (AR), we show that local infusion of clonidine, an α2-AR agonist, induced a switch from tonic to bursty pattern without changing the firing rate. This change in the pattern was prevented by the local infusion of idazoxan, an α2-AR antagonist. Furthermore, clonidine injection into the STN reduced locomotor activity in sham and 6-hydroxydopamine-lesioned rats. In contrast, local injection of phenylephrine, an α1-AR agonist, increased the firing rate of STN neurons without changing the firing pattern. In parallel, phenylephrine did not change locomotor activity. This is the first evidence showing the implication of α1-ARs in the modulation of firing rate and α2-ARs in the modulation of the firing pattern of STN neurons. Furthermore, our data provide also evidence that activation of the STN α2-ARs plays a key role in the genesis of subthalamic burst activity, which may be at the origin of motor deficits.
Keywords:
Norepinephrine,
Parkinson Disease,
Subthalamic Nucleus,
motor control,
Neurophysiology
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Delaville
C,
Faggiani
E,
Cardoit
L and
Benazzouz
A
(2013). Noradrenergic control of the subthalamic nucleus.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00021
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Received:
26 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Dr. Abdelhamid Benazzouz, Univ. Bordeaux, Neurodegenerative Diseseases Institute/CNRS UMR 5293, Bordeaux, 33076, France, abdelhamid.benazzouz@u-bordeaux2.fr