Selective direct motor cortical influence during naturalistic climbing.

It remains poorly resolved when and how motor cortical output directly influences limb muscle activity through descending projections, which impedes mechanistic understanding of cortical movement control. Here we addressed this in mice performing an ethologically inspired all-limb climbing behavior. We quantified the direct influence of forelimb primary motor cortex (caudal forelimb area, CFA) on muscle activity comprehensively across the muscle activity states that occur during climbing. We found that CFA informs muscle activity pattern, mainly by selectively activating certain muscles while exerting much smaller, bidirectional effects on their antagonists. From Neuropixel recordings, we identified linear combinations (components) of motor cortical activity that covary with these effects, finding that these components differ from those that covary with muscle activity or 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 new type of neural activity subspace.