Funding agencies: This work was supported by the National Institutes of Health (grant nos.: NS20576 and F31MH10812).
Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata
Article first published online: 31 OCT 2012
Copyright © 2012 Movement Disorders Society
Volume 28, Issue 4, pages 460–468, April 2013
How to Cite
Dybdal, D., Forcelli, P. A., Dubach, M., Oppedisano, M., Holmes, A., Malkova, L. and Gale, K. (2013), Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata. Mov. Disord., 28: 460–468. doi: 10.1002/mds.25215
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 8 APR 2013
- Article first published online: 31 OCT 2012
- Manuscript Accepted: 30 AUG 2012
- Manuscript Revised: 7 AUG 2012
- Manuscript Received: 26 MAR 2012
- subthalamic nucleus;
- substantia nigra pars reticulata;
- Huntington's disease;
- choreiform movements;
- GABA receptors;
- basal ganglia;
GABAergic neurons of the substantia nigra pars reticulata (SNpr) and globus pallidus pars interna (GPi) constitute the output pathways of the basal ganglia. In monkeys, choreiform limb dyskinesias have been described after inhibition of the GPi, but not the SNpr. Given the anatomical and functional similarities between these structures, we hypothesized that choreiform dyskinesias could be evoked by inhibition of an appropriate region within the SNpr. The GABAA receptor agonist, muscimol, was infused into various sites within the SNpr and the adjacent STN of freely moving macaques. The effect of the GABAA antagonist, bicuculline (BIC), was also examined. Muscimol (MUS) in SNpr evoked the following: (1) choreiform dyskinesias of the contralateral arm and/or leg from central and lateral sites; (2) contralaterally directed torticollis from central and posterior sites; and (3) contraversive quadrupedal rotation from anterior and lateral sites. MUS infusions into the adjacent SN pars compacta or STN were without effect, ruling out a contribution of drug spread to adjacent structures. BIC in SNpr induced ipsiversive postures without choreiform dyskinesia or torticollis, whereas in the STN, it evoked ballistic movements. This is the first report of choreiform dyskinesia evoked by inhibition of the SNpr. This highly site-specific effect was obtained from a restricted region within the SNpr distinct from that responsible for inducing torticollis. These results suggest that overactivity of different SNpr outputs mediates choreiform dyskinesia and torticollis. These abnormalities are symptoms of dystonia, Huntington's disease, and iatrogenic dyskinesias, suggesting that these conditions may result, in part, from a loss of function in SNpr efferent projections. © 2012 Movement Disorder Society