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J Neurophysiol (December 17, 2003). doi:10.1152/jn.01124.2002
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Submitted on December 13, 2002
Accepted on November 8, 2003

The Effects of Muscimol Inactivation of the Cerebellar Nuclei on Precision Grip

Joel Monzee1, Trevor Drew1, and Allan M. Smith1*

1 Physiologie, Universite de Montreal, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: allan.smith{at}umontreal.ca.

A single monkey was trained to perform a grasp, lift, and hold task in which a stationary handheld 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 in order to quantify specific motor deficits after reversible inactivation of the cerebellar nuclei. A prior single cell recording study in the same monkey (Monzee and Smith companion paper) provided the stereotaxic coordinates used to guide intra-nuclear injections of muscimol. In total, 34 penetrations were performed at 28 different loci throughout the cerebellar nuclei. On each penetration, two 1.0µl,injections of 5µg/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.




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