Transition of distinct context-dependent ensembles from secondary to primary motor cortex in skilled motor performance.

When voluntary movements are executed under different contexts, different context-dependent signals are thought to weaken from secondary motor cortex (M2) to primary motor cortex (M1). However, it is unclear how the different contexts are processed from M2 to M1 to execute skilled movement. We conduct two-photon calcium imaging of M2 and M1 in mice performing internally generated and external-cue-triggered movements. Context dependency is consistently high in M2 L2/3 neurons and consistently low in M1 pyramidal tract neurons. By contrast, context dependency in M2 → M1 axons and M1 L2/3 neurons increases as task performance improves. In addition, the context dependency of M1 L2/3, but not M2 → M1 axons, is associated with fine-movement proficiency. The increase in context dependency correlates with stabilization of the context-dependent population activity and an increase in the neurons that strongly encode contextual and motor information. Thus, emergence of distinct context-dependent ensembles may be necessary for the context-to-motor transformation that facilitates skilled motor performance.