Corticothalamic neurons in motor cortex have a permissive role in motor execution

The primary motor cortex (M1) is a central hub for motor learning and execution. M1 is composed of heterogeneous cell types with varying relationships to movement. Here, we tagged active neurons at different stages of motor task performance in mice and characterized cell type composition. We identified corticothalamic neurons (M1(CT)) as consistently enriched with training progression. Using two-photon calcium imaging, we found that M1(CT) activity is largely suppressed during movement, and this negative correlation augments with training. Increasing M1(CT) activity through closed-loop optogenetic manipulations during forelimb movement significantly hinders execution, an effect that became stronger with training. Similar manipulations, however, had little effect on locomotion. In contrast, M1 corticospinal neurons positively correlate with movement, with an increase during training. We uncovered that M1(CT) neurons suppress corticospinal activity via feedforward inhibition, also scaling with training. These results identify a permissive role of corticothalamic neurons in movement execution through disinhibition of corticospinal neurons.