Cortical Control of Adaptive Locomotion in Wild-Type Mice and Mutant Mice Lacking the Ephrin-Eph Effector Protein α2-Chimaerin

Abstract

In voluntary control, supraspinal motor systems select the appropriate response and plan movement mechanics to match task constraints. Spinal circuits translate supraspinal drive into action. We studied the interplay between motor cortex (M1) and spinal circuits during voluntary movements in wild-type (WT) mice and mice lacking the α2-chimaerin gene (Chn1−/−), necessary for ephrinB3-EphA4 signaling. Chn1−/− mice have aberrant bilateral corticospinal systems, aberrant bilateral-projecting spinal interneurons, and disordered voluntary control because they express a hopping gait, which may be akin to mirror movements. We addressed three issues. First, we determined the role of the corticospinal system in adaptive control. We trained mice to step over obstacles during treadmill locomotion. We compared performance before and after bilateral M1 ablation. WT mice adaptively modified their trajectory to step over obstacles, and M1 ablation increased substantially the incidence of errant steps over the obstacle. Chn1−/− mice randomly stepped or hopped during unobstructed locomotion but hopped over the obstacle. Bilateral M1 ablation eliminated this obstacle-dependent hop selection and increased forelimb obstacle contact errors. Second, we characterized the laterality of corticospinal action in Chn1−/− mice using pseudorabies virus retrograde transneuronal transport and intracortical microstimulation. We showed bilateral connections between M1 and forelimb muscles in Chn1−/− and unilateral connections in WT mice. Third, in Chn1−/− mice, we studied adaptive responses before and after unilateral M1 ablation. We identified a more important role for contralateral than ipsilateral M1 in hopping over the obstacle. Our findings suggest an important role for M1 in the mouse in moment-to-moment adaptive control, and further, using Chn1−/− mice, a role in mediating task-dependent selection of mirror-like hopping movements over the obstacle. Our findings also stress the importance of subcortical control during adaptive locomotion because key features of the trajectory remained largely intact after M1 ablation.