Parkinson’s disease (PD) affects the basal ganglia system, which causes movement dysfunction. Despite its crucial role in integrating basal ganglia calculations with motor function, the primary motor cortex’s contribution to motor impairment in PD is little unknown. For a study, researchers wanted to determine the function of the primary motor cortex in motor impairment caused by Parkinson’s disease. During the execution of a dexterous reach-to-grasp motor task in control and 6-hydroxydopamine-induced PD mice, two-photon calcium imaging and optogenetic activation of primary motor cortex neurons were performed. The reach-to-grasp motor task was disturbed by experimental PD, particularly the task’s beginning, which was partially recovered by optogenetic stimulation of the primary motor cortex. Experimental PD altered the primary motor cortex in a cell-type-specific way, according to two-photon calcium imaging during task performance. It reduced the activity of output layer 5 pyramidal tract neurons, with the effects being stronger in freeze trials than in non-freeze trials. In contrast, it did not reduce the late inhibitory phase of layer 2/3 pyramidal neurons’ response while increasing the early movement-related activation response. At the network level, experimental PD affected the layer 5 pyramidal tract network’s movement-related population dynamics while having no effect on the layer 2/3 neuronal population.

Both external driving and intrinsic features of the primary motor cortex are disrupted in experimental PD. The failure to create strong and consistent output motor sequences in the parkinsonian primary motor cortex output layer 5 pyramidal tract subnetwork causes motor impairment in experimental PD.