title: Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata.
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.
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Holmes
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Forcelli
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: DesJardin
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Decker
authors.forename: Menna
authors.initials: M
authors.lastname: Teferra
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: West
authors.forename: Ludise
authors.initials: L
authors.lastname: Malkova
authors.forename: Karen
authors.initials: K
authors.lastname: Gale
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005260:Female; D058785:GABA-A Receptor Agonists / Q000627:therapeutic use / Q000633:toxicity; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D019416:Head Movements / Q000187:drug effects; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D009068:Movement / Q000187:drug effects; D009118:Muscimol / Q000627:therapeutic use / Q000633:toxicity; D004856:Postural Balance / Q000187:drug effects; D012678:Sensation Disorders / Q000188:drug therapy / Q000209:etiology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology*; D013477:Superior Colliculi / Q000187:drug effects / Q000502:physiology*; D014103:Torticollis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D009118:Muscimol; D001640:Bicuculline