Selective direct motor cortical influence during naturalistic climbing in mice.

It remains poorly resolved when and how motor cortical output directly influences limb muscle activity through descending projections, which impedes mechanistic understanding of motor control. Here we addressed this in mice performing an ethologically inspired climbing behavior. We quantified the direct influence of forelimb primary motor cortex (caudal forelimb area, CFA) on muscles across the muscle activity states expressed during climbing. We found that CFA instructs muscle activity pattern by selectively activating certain muscles, while less frequently activating or suppressing their antagonists. From Neuropixels recordings, we identified linear combinations (components) of motor cortical activity that covary with these effects. These components differ partially from those that covary with muscle activity and differ almost completely from those that covary with kinematics. Collectively, our results reveal an instructive direct motor cortical influence on limb muscles that is selective within a motor behavior and reliant on a distinct neural activity subspace.