Bilateral alteration in stepping pattern after unilateral motor cortex injury: A new test strategy for analysis of skilled limb movements in neurological mouse models

Mice are becoming increasingly popular to model neurological disease and motor system dysfunction. For evaluation of discrete, chronic motor impairments, skilled limb movements represent a valuable extension of standard mouse test batteries. This study introduces an efficient and sensitive test strategy for comprehensive assessment of skilled fore- and hind-limb stepping in mice. Adult C57BL/6 mice were trained and video-recorded in two walking tasks, the widely used rotorod test and a new ladder rung task. The animals then received a unilateral ischemic lesion in the motor cortex forelimb and hind limb area and were video-recorded on days 12 and 26 post-lesion. Forelimb and hind limb stepping movements were rated using a combination of endpoint measures and qualitative assessment. The results showed that while animals maintained a weight-supported gait, posture and stepping movements were abnormal at both post-operative intervals. The rotorod analysis revealed stepping deficits in both forelimbs that led to adoption of compensatory movement strategies. The ladder rung task revealed stepping errors in ipsi- and contralateral fore- and hind-limbs. The findings demonstrate that this test strategy provides comprehensive assessment of motor impairments in mice and that qualitative movement analysis is a valuable tool for elaborating subtle motor disturbances.