LAUSR

Significance Which brain area drives hand/arm movements after learning or brain injury? When does motor cortical activity generate appropriate hand/arm movements? To address these issues, it is necessary to manipulate motor cortical activity in a controlled manner. Optogenetic tools allow neuronal activity to be manipulated in a variety of animals, but forelimb movements in nonhuman primates have not previously been optogenetically induced or modulated. Here, we improved a method of optogenetic cortical stimulation and induced overt forelimb movements in the common marmoset, a New World monkey. Photostimulation also modulated voluntary forelimb movements, with the modulated movement trajectories depending on the stimulation site and timing. Our results open doors for noninvasive interrogation of motor circuits in behaving nonhuman primates. Optogenetics is now a fundamental tool for investigating the relationship between neuronal activity and behavior. However, its application to the investigation of motor control systems in nonhuman primates is rather limited, because optogenetic stimulation of cortical neurons in nonhuman primates has failed to induce or modulate any hand/arm movements. Here, we used a tetracycline-inducible gene expression system carrying CaMKII promoter and the gene encoding a Channelrhodopsin-2 variant with fast kinetics in the common marmoset, a small New World monkey. In an awake state, forelimb movements could be induced when Channelrhodopsin-2−expressing neurons in the motor cortex were illuminated by blue laser light with a spot diameter of 1 mm or 2 mm through a cranial window without cortical invasion. Forelimb muscles responded 10 ms to 50 ms after photostimulation onset. Long-duration (500 ms) photostimulation induced discrete forelimb movements that could be markerlessly tracked with charge-coupled device cameras and a deep learning algorithm. Long-duration photostimulation mapping revealed that the primary motor cortex is divided into multiple domains that can induce hand and elbow movements in different directions. During performance of a forelimb movement task, movement trajectories were modulated by weak photostimulation, which did not induce visible forelimb movements at rest, around the onset of task-relevant movement. The modulation was biased toward the movement direction induced by the strong photostimulation. Combined with calcium imaging, all-optical interrogation of motor circuits should be possible in behaving marmosets.