Motor cortical influence relies on task-specific activity covariation

During limb movement, spinal circuits facilitate the alternating activation of antagonistic flexor and extensor muscles. Yet antagonist cocontraction is often required to stabilize joints, like when loads are handled. Previous results suggest that these different muscle activation patterns are mediated by separate flexion- and extension-related motor cortical output populations, while others suggest recruitment of task-specific populations. To distinguish between hypotheses, we developed a paradigm in which mice toggle between forelimb tasks requiring antagonist alternation or cocontraction and measured activity in motor cortical layer 5b. Our results conformed to neither hypothesis: consistent flexion- and extension-related activity was not observed across tasks, and no task-specific populations were observed. Instead, activity covariation among motor cortical neurons dramatically changed between tasks, thereby altering the relation between neural and muscle activity. This was also observed specifically for corticospinal neurons. Collectively, our findings indicate that motor cortex drives different muscle activation patterns via task-specific activity covariation. HIGHLIGHTSO_LIMice perform two forelimb tasks involving distinct antagonist muscle activity in a novel paradigm C_LIO_LIL5b motor cortical neurons are not organized by task-specific activity C_LIO_LIL5b motor cortical neurons do not encode muscle activity consistently across tasks C_LIO_LITask-specific muscle activity is driven by a change in motor cortical activity covariation C_LI eTOC BLURBWarriner et al. simultaneously measured muscle and motor cortical activity in mouse during antagonist forelimb muscle alternation and cocontraction, revealing that these distinct muscle activation patterns are not driven through consistent flexion and extension programs nor through the activity of discrete, task-specific neuronal subsets. Instead, distinct patterns involve task-specific changes in firing pattern covariation among layer 5b neurons, and corticospinal neurons in particular, which change their relationship to muscle activity across tasks.