Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NINDS	PHARM/PHYS-3

Authors

• A.H. Holmes
• P.A. Forcelli
• J.T. DesJardin
• A.L. Decker
• M. Teferra
• E. West
• L. Malova
• K. Gale

Abstract

Inhibition of substantia nigra pars reticulata (SNpr) in nonhuman primates has been found to evoke cervical dystonia (CD) (Burbaud et al., 1998; Dybdal, 1999). Because inhibition of SNpr results in suppression of GABAergic neurons that project from this region, thereby disinhibiting the targets of these outputs, it should be possible to prevent CD by inhibition of an appropriate target. Here we tested the hypothesis that the superior colliculus, and more specifically the deep and intermediate layers (DLSC), is required for the emergence of CD. To test this hypothesis, we pretreated the DLSC of four macaques with the GABA-A agonist muscimol in order to determine whether this treatment could prevent the CD in response to muscimol infusions in SNpr. We found that inhibition of DLSC consistently attenuated SNpr-evoked CD, supporting our proposal that the DLSC mediates CD evoked by inhibition of the SNpr. Our results are the first to demonstrate a role of the DLSC in the expression of CD, and to reveal a functional relationship between SNpr and DLSC in mediating posture and movement in the nonhuman primate. Our results also suggest that it would be worth considering the nigrotectal pathway as a potential target for therapeutic interventions for CD.

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