Effects of Muscimol Inactivation of the Cerebellar Nuclei on Precision Grip

Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, Montreal H3C 3T8, Canada Submitted 13 December 2002; accepted in final form 8 November 2003 A single monkey was trained to perform a grasp, lift, and hold task in which a stationary hand- held object was sometimes subjected to brief, predictable force-pulse perturbations. The displacement, grip, and lifting forces were measured as well the three-dimensional forces and torques to quantify specific motor deficits after reversible inactivation of the cerebellar nuclei. A prior single-cell recording study in the same monkey provided the stereotaxic coordinates used to guide intranuclear injections of muscimol. In total, 34 penetrations were performed at 28 different loci throughout the cerebellar nuclei. On each penetration, two 1.0-µl injections of 5 µg/µl muscimol, were made 1.0 mm apart either within the nuclei or in the white matter just lateral or posterior to the dentate nucleus. Injections in the region corresponding to the anterior interpositus nucleus produced pronounced dynamic tremor and dysmetric movements of the ipsilateral arm when the animal performed unrestrained reaching and grasping movements. In contrast, no relatively short-latency (15-20 min.) deficits were observed after injection in the dentate nucleus, although some effects were observed after several hours. When tested in a primate chair with the forearm supported and restrained at the wrist and elbow, the monkey performed the lift and hold task without tremor or dysmetria. However, with the restraint removed, the forces and torques applied to the manipulandum were poorly controlled and erratic. The monkey's arm was ataxic and a 5-Hz intention tremor was clearly visible. In addition, the animal was generally unable to compensate for the predictable perturbations and the anticipatory grip force increases were absent. However, overall the results suggest that reversible cerebellar nuclear inactivation with muscimol has little effect on isolated distal movements of the wrist and fingers. Address reprint requests and other correspondence to: A. M. Smith, Centre de Recherche en Sciences Neurologiques, Dépt. de Physiologie, Université de Montréal, C.P. 6128 Succursale Centre ville, Montréal, Québec H3C 3T8, Canada (E-mail: allan.smith{at}umontreal.ca ).