Cerebellectomy eliminates the motor syndrome of the genetically dystonic rat

The genetically dystonic (dt) rat is a neurological mutant that displays a movement disorder characterized by repetitive twisting movements of the trunk and limbs. Previous work has identified the cerebellum of the dt rat as a site of biochemical, metabolic, and functional abnormality. In order to test the hypothesis that a cerebellar defect is critical to the expression of the motor syndrome, groups of dt rats and phenotypically normal littermates underwent cerebellectomy (CBX) at either 15 or 20 days of age. The performance of these animals on a battery of motor tasks was compared with their preoperative performance. Age-matched unoperated rats of the same phenotype and a group of dt rats with lesions in the entopeduncular nuclei (ENTO) served as controls. In dt rats, CBX permanently eliminated all motor signs of the disease except pivoting movements without reducing overall levels of activity. In the dt rats, CBX also caused significant improvement in several tests of motor function. The ENTO group, however, showed an increase in motor signs and no improvement in motor function. The results of this study provide the first evidence that the abnormalities detected in the cerebellum of the dt rat are causally related to the motor syndrome and suggest that abnormal cerebellar output may contribute to the expression of motor signs in some human dystonias.