Locomotor deficits in the mutant mouse, Lurcher.

Abstract

The effect of total Purkinje cell degeneration on treadmill locomotion was studied in the cerebellar mutant mouse Lurcher. Other movements such as swimming and scratching were also studied in order to evaluate the cerebellar control of rhythmic actions. Cinematographic and electromyographic recordings were taken from normal and Lurcher mice that were subsequently perfused to obtain a Purkinje cell count. Walking deteriorated progressively and was clearly abnormal in 30 day old Lurchers with 90% Purkinje cell degeneration. In adult Lurcher mice in which Purkinje cells were totally absent, walking was characterized by short steps with exaggerated hindlimb flexion in the swing phase. Also, both the interlimb step ratio, defined as the step length of the reference limb divided by the step length of the opposite limb, and the interlimb coupling, defined as the temporal relation of one footfall with respect to the footfall of another limb, varied more than in normal mice. Furthermore, the locomotion of Lurcher mice displayed increased vertical displacement of the hip and an inability to produce continuous step cycles without stumbling. Both the EMG onset relative to foot contact and the EMG burst duration were highly variable, and a greater overlap in the activities of antagonist muscles at the transition from ankle extension to flexion was evident. Although both walking and swimming involve cyclical limb movements, the disorganization of the cycle and the irregular EMG pattern seen in the Lurcher during walking were not observed during swimming. Furthermore, scratching was well executed in the Lurcher mice. However, a consistently higher tonic extensor activity at the ankle appeared during walking, swimming and scratching. These results suggest that, in contrast to swimming and scratching, the requirements of walking depend to a greater degree on a functional cerebellar cortex for successful performance.