Abstract
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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
In this revised manuscript, we clarify methodology and expand on results previously reported. The manuscript provides technically rigorous support for several new conclusions: first, that during an ethologically relevant motor behavior, motor cortical output instructs forelimb muscle activity patterns, doing so by selectively exciting activity in certain muscles while exerting much smaller and bidirectional effects on their antagonists; second, that comprehensively throughout the full range of limb and limb muscle activity states that occur during climbing, motor cortical influence covaries much more strongly with muscle activity than limb kinematics, addressing a long-running debate in the field; third, that a substantial number of motor cortical neurons across all layers are active primarily during a small fraction of muscle activity states, somewhat like CA1 place cells, and inconsistent with contemporary ideas that motor cortical control relies on a low- dimensional subspace; and finally, that motor cortical influence is mediated by a neural activity subspace distinct from those to which functional significance is commonly ascribed.
