An output-null signature of inertial load in motor cortex

Coordinated movement requires the nervous system to continuously compensate for changes in mechanical load across different contexts. For voluntary movements like reaching, the motor cortex is a critical hub that generates commands to move the limbs and counteract loads. How does cortex contribute to load compensation when rhythmic movements are clocked by a spinal pattern generator? Here, we address this question by manipulating the mass of the forelimb in unrestrained mice during locomotion. While load produces changes in motor output that are robust to inactivation of motor cortex, it also induces a profound shift in cortical dynamics, which is minimally affected by cerebellar perturbation and significantly larger than the response in the spinal motoneuron population. This latent representation may enable motor cortex to generate appropriate commands when a voluntary movement must be integrated with an ongoing, spinally-generated rhythm.