The role of motor cortex in motor sequence execution depends on demands for flexibility

The role of the motor cortex in executing motor sequences is widely debated, with studies supporting disparate views. Here we probe the degree to which the motor cortex’s engagement depends on task demands, specifically whether its role differs for highly practiced, or ‘automatic’, sequences versus flexible sequences informed by external cues. To test this, we trained rats to generate three-element motor sequences either by overtraining them on a single sequence or by having them follow instructive visual cues. Lesioning motor cortex showed that it is necessary for flexible cue-driven motor sequences but dispensable for single automatic behaviors trained in isolation. However, when an automatic motor sequence was practiced alongside the flexible task, it became motor cortex dependent, suggesting that an automatic motor sequence fails to consolidate subcortically when the same sequence is produced also in a flexible context. A simple neural network model recapitulated these results and offered a circuit-level explanation. Our results critically delineate the role of the motor cortex in motor sequence execution, describing the conditions under which it is engaged and the functions it fulfills, thus reconciling seemingly conflicting views about motor cortex’s role in motor sequence generation.