Arm movements induced by noninvasive optogenetic stimulation of the motor cortex in the common marmoset
Arm movements induced by noninvasive optogenetic stimulation of the motor cortex in the common marmoset
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DOI：
10.1073/pnas.1903445116
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发表时间：
2019-11-05
影响因子：
11.1
通讯作者：
Matsuzaki, Masanori
中科院分区：
文献类型：
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作者：
Ebina, Teppei;Obara, Keitaro;Matsuzaki, Masanori
光遗传学现在是研究神经元活动和行为之间关系的基本工具。然而，它在非人灵长类动物运动控制系统研究中的应用相当有限，因为非人灵长类动物皮质神经元的光遗传刺激未能诱导或调节任何手/手臂运动。在这里，我们使用了一个四环素诱导的基因表达系统，该系统携带CaMKII启动子和编码通道视紫红质-2的基因，在普通狨猴（一种小型新大陆猴）中具有快速动力学。在清醒状态下，用光斑直径为1 mm或2 mm的蓝色激光穿过颅窗照射运动皮层表达通道视紫红质-2的神经元，可诱导前肢运动。前肢肌肉在光刺激开始后10 ms至50 ms有反应。长时间（500毫秒）的光刺激诱导前肢离散运动，可以用电荷耦合器件相机和深度学习算法无标记地跟踪。长时间光刺激图谱显示，初级运动皮层分为多个区域，可以诱导手和肘部在不同方向上的运动。在前肢运动任务的执行过程中，运动轨迹受到弱光刺激的调节，在任务相关运动开始前后，弱光刺激不会引起休息时可见的前肢运动。这种调制偏向于强光刺激引起的运动方向。与钙成像相结合，对行为正常的狨猴的运动回路进行全光探测应该是可能的。
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.