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High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson’s disease

Mathieu Favier12, Carole Carcenac12, Guillaume Drui12, Sabrina Boulet12, Salah El Mestikawy4567 and Marc Savasta123*

Author Affiliations

1 Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9, France

2 Université de Grenoble, Grenoble F- 38042, France

3 Centre Hospitalier Universitaire de Grenoble, BP217, Grenoble F-38043, France

4 Institut National de la Santé et de la Recherche Médicale (INSERM), U952, Université Pierre et Marie Curie, Paris F-75005, France

5 Centre National de la Recherche Scientifique (CNRS) UMR 7224, Paris F-75005, France

6 Université Pierre et Marie Curie (UPMC) Paris 06, Pathophysiology of Central Nervous System Disorders, Paris F-75005, France

7 Department of Psychiatry, Douglas Hospital Research Center, McGill University, 6875, boulevard Lasalle, Verdun, QC, Canada

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BMC Neuroscience 2013, 14:152  doi:10.1186/1471-2202-14-152

Published: 5 December 2013



It has been suggested that glutamatergic system hyperactivity may be related to the pathogenesis of Parkinson’s disease (PD). Vesicular glutamate transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key anatomical and functional markers of glutamatergic excitatory transmission. Both VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and VGLUT2 are thought to be expressed in a complementary manner in the cortex and the thalamus (VL/VM), in glutamatergic neurons involved in different physiological functions. Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced PD. STN-HFS is highly effective, but its mechanisms of action remain unclear. This study examines the effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in motor circuits, namely the basal ganglia (BG) network, in normal and 6-hydroxydopamine (6-OHDA) lesioned rats.


Here we report that: 1) Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but significantly decreased that of VGLUT2 in almost all BG structures studied; 2) STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal rats while, on the contrary, it systematically induced a significant increase of their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in VGLUT2 expression induced by the DA-depletion.


These results show for the first time a comparative analysis of changes of expression for the three VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats. They provide evidence for the involvement of VGLUT2 in the modulation of BG cicuits and in particular that of thalamostriatal and thalamocortical pathways suggesting their key role in its therapeutic effects for alleviating PD motor symptoms.

High frequency stimulation; Subthalamic nucleus; Parkinson’s disease; Basal Ganglia; 6-OHDA-lesion; Rat; Glutamate; Vesicular glutamate transporters