Locomotor deficits in the mutant mouse, Lurcher

Area of Science:

• Neuroscience
• Motor Control
• Animal Models

Background:

• The cerebellum plays a crucial role in coordinating complex motor behaviors.
• Purkinje cells are key components of the cerebellar cortex involved in motor learning and execution.
• The Lurcher mouse mutant exhibits progressive Purkinje cell loss, providing a model to study cerebellar function.

Purpose of the Study:

• To investigate the impact of complete Purkinje cell degeneration on treadmill locomotion in Lurcher mice.
• To evaluate the cerebellar control of rhythmic actions by comparing walking, swimming, and scratching behaviors.

Main Methods:

• Cinematographic and electromyographic (EMG) recordings were utilized in normal and Lurcher mice.
• Purkinje cell counts were determined post-mortem after perfusion.
• Analysis focused on gait parameters, limb coordination, and muscle activity patterns during locomotion.

Main Results:

• Progressive deterioration of walking was observed with increasing Purkinje cell loss.
• Adult Lurcher mice with total Purkinje cell absence displayed abnormal gait, including short steps, exaggerated hindlimb flexion, and increased hip displacement.
• While walking showed significant disorganization and variable EMG patterns, swimming and scratching were relatively well-preserved, though increased tonic extensor activity was noted across all tasks.

Conclusions:

• Successful execution of treadmill walking critically depends on a functional cerebellar cortex, unlike swimming and scratching.
• Purkinje cell degeneration profoundly disrupts the complex coordination required for terrestrial locomotion.
• The cerebellum's role in motor control is task-dependent, with locomotion being particularly sensitive to Purkinje cell loss.