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Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2012 Sep 19; Vol. 32 (38), pp. 13326-32. - Publication Year :
- 2012
-
Abstract
- Cervical dystonia (CD; spasmodic torticollis) can be evoked by inhibition of substantia nigra pars reticulata (SNpr) in the nonhuman primate (Burbaud et al., 1998; Dybdal et al., 2012). Suppression of GABAergic neurons that project from SNpr results in the disinhibition of the targets to which these neurons project. It therefore should be possible to prevent CD by inhibition of the appropriate nigral target region(s). Here we tested the hypothesis that the deep and intermediate layers of the superior colliculus (DLSC), a key target of nigral projections, are required for the emergence of CD. To test this hypothesis, we pretreated the DLSC of four macaques with the GABA(A) agonist muscimol to determine whether this treatment would prevent CD evoked by muscimol infusions in SNpr. Our data supported this hypothesis: inhibition of DLSC attenuated CD evoked by muscimol in SNpr in all four animals. In two of the four subjects, quadrupedal rotations were evoked by muscimol application into SNpr sites that were distinct from those that induced dystonia. We found that inhibition of DLSC did not significantly alter quadrupedal rotations, suggesting that this response is dissociable from the SNpr-evoked CD. Our results are the first to demonstrate a role of DLSC in mediating the expression of CD. Furthermore, these data reveal a functional relationship between SNpr and DLSC in regulating posture and movement in the nonhuman primate, raising the possibility that the nigrotectal pathway has potential as a target for therapeutic interventions for CD.
- Subjects :
- Analysis of Variance
Animals
Bicuculline pharmacology
Bicuculline therapeutic use
Disease Models, Animal
Drug Administration Routes
Female
GABA-A Receptor Agonists therapeutic use
GABA-A Receptor Agonists toxicity
GABA-A Receptor Antagonists pharmacology
GABA-A Receptor Antagonists therapeutic use
Head Movements drug effects
Macaca mulatta
Magnetic Resonance Imaging
Male
Movement drug effects
Muscimol therapeutic use
Muscimol toxicity
Postural Balance drug effects
Sensation Disorders drug therapy
Sensation Disorders etiology
Substantia Nigra drug effects
Superior Colliculi drug effects
Torticollis chemically induced
Torticollis physiopathology
Substantia Nigra physiopathology
Superior Colliculi physiology
Torticollis pathology
Torticollis prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 32
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 22993447
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.2295-12.2012