Pallidal origin of GABA release within the substantia nigra pars reticulata during high-frequency stimulation of the subthalamic nucleus

Windels, François, Carcenac, Carole, Poupard, Annie and Savasta, Marc (2005) Pallidal origin of GABA release within the substantia nigra pars reticulata during high-frequency stimulation of the subthalamic nucleus. Journal of Neuroscience, 25 20: 5079-5086. doi:10.1523/JNEUROSCI.0360-05.2005

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Author Windels, François
Carcenac, Carole
Poupard, Annie
Savasta, Marc
Title Pallidal origin of GABA release within the substantia nigra pars reticulata during high-frequency stimulation of the subthalamic nucleus
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
1529-2401
Publication date 2005-05-18
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.0360-05.2005
Open Access Status File (Publisher version)
Volume 25
Issue 20
Start page 5079
End page 5086
Total pages 8
Place of publication Washigton, DC, United States
Publisher Society for Neuroscience
Language eng
Subject 1109 Neurosciences
Abstract High-frequency stimulation of the subthalamic nucleus (HFS-STN) is an effective treatment for alleviating the motor symptoms of parkinsonian patients. However, the neurochemical basis of its effects remains unknown. We showed previously that 1 h of HFS-STN in normal rats increases extracellular glutamate (Glu) level in the output nuclei of the STN, the globus pallidus (GP), and the substantia nigra pars reticulata (SNr), consistent with an increase in the activity of STN neurons. HFS-STN also increases GABA levels in the SNr, but the origin of this increase is unclear. We investigated the effectiveness of HFS-STN for improving Parkinson's disease symptoms, using intracerebral microdialysis to determine the extracellular Glu and GABA levels of the GP and SNr in response to HFS-STN in anesthetized hemiparkinsonian rats [6-hydroxydopamine lesion of the substantia nigra pars compacta (SNc)]. Basal levels of Glu and GABA in the GP and SNr were significantly higher in hemiparkinsonian than in intact rats. HFS-STN did not affect extracellular Glu level in the SNr of hemiparkinsonian rats but doubled the level of GABA. Ibotenic acid lesion of the GP abolished the increase in GABA levels in the SNr induced by HFS-STN in SNc-lesioned rats. These results provide neurochemical confirmation of the hyperactivity of the STN after dopaminergic denervation and suggest that the therapeutic effects of HFS-STN may result partly from the stimulation of pallidonigral fibers, thereby revealing a potential role for pallidal GABA in the inhibition of basal ganglial output structures during HFS-STN.
Keyword Neurosciences
Subthalamic nucleus
Substantia nigra pars reticulata
Glutamate
GABA
Basal ganglia
High-frequency deep brain stimulation
Parkinson's disease
Microdialysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
ERA 2012 Admin Only
 
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Created: Sat, 26 Jan 2008, 02:34:08 EST