Corticothalamic Neurons in Motor Cortex Have a Permissive Role in Motor Execution

Abstract

ABSTRACTThe primary motor cortex (M1) is a central hub for motor learning and execution, as it receives input from and broadcasts to a multitude of other motor regions. It has become increasingly clear that M1 is heterogeneous in terms of cell types, many of which exhibit varying relationships to movement during learning and execution. Previous studies have mainly used a single candidate approach to identify cell types contributing to motor learning and execution. Here, we employed an unbiased screen to tag active neurons at different stages of performance of a motor task. We characterized the relative cell type composition among the active neurons at different stages of motor training and identified varying patterns across training. One cell type consistently showed enrichment as training and execution progressed: corticothalamic neurons (M1CT). Anatomical characterization of M1CT neurons revealed an extensive projection pattern to thalamic nuclei with marked topographical organization. Using two-photon calcium imaging, we found that M1CT neuron activity is largely suppressed during movement. M1CT neurons display a negative correlation with movement that scales with movement vigor and augments with training. Closed-loop optogenetic manipulation of M1CT activity revealed that their activity rapidly affects movement execution, even after movement is initiated. Taken together, these results identify and reveal a critical permissive role of corticothalamic neurons in movement execution.