Activation of subthalamic alpha 2 noradrenergic receptors induces motor deficits as a consequence of neuronal burst firing

Claire Delaville, Jonathan Zapata, Laura Cardoit, Abdelhamid Benazzouz
Neurobiology of Disease. 2012-09-01; 47(3): 322-330
DOI: 10.1016/j.nbd.2012.05.019

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Delaville C(1), Zapata J, Cardoit L, Benazzouz A.

Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, 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.

Copyright © 2012 Elsevier Inc. All rights reserved.

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