Characterizing long-range cortical and subcortical dynamics in relation to corticospinal output and motor control

摘要 即使是一个简单的运动，如前肢的伸展或弯曲，也需要激活，需要输入 来自不同大脑区域的许多不同神经群的活动传递到运动控制中心， 控制肌肉活动。尽管许多大脑区域已经被证明具有与运动相关的活动， 参与运动准备和执行，这些大脑区域的活动与运动之间的关系， 大脑向脊髓的输出仍然难以捉摸。因此，绝对有必要描述 来自其他皮质和皮质下区域的上游神经群体对神经元活动的贡献 在项目1中表征的皮质脊髓神经元的投射特异性群体，在不同的模式下， 运动控制我们建议使用一系列功能成像方法进行这种表征， 在不同的尺度上研究这个问题。我们将利用宽视场光学映射（WFOM）成像，在一个 无偏见的方式，活动数百至数千个细胞在许多皮层地区的关系， 特定CSN的活动，其代表皮层到脊髓的输出。 通过WFOM成像，我们将同时对神经元群体进行成像， 单细胞分辨率，在不同的大脑区域使用2光子随机访问介观（2 p-RAM）成像。 最后，我们建议使用2 pRAM介观镜同时成像丘脑或纹状体的活动 通过GRIN透镜，和皮质脊髓神经元的活动，在特定的运动控制模式。 在这个项目中获得的知识将是至关重要的了解原则，在运动皮层的活动 与项目3中提出的与运动输出有关的其他皮层区域相比， 项目4中的模型。此外，它将有助于生成将使用闭环测试的预测 项目5中的光遗传学操作实验。

Abstract Even a simple movement, like the extension or flexion of a forelimb, requires the activation requires the input of activity from many different neural populations across different brain areas onto motor control centers that control muscle activity. Although many brain areas have been shown to have motor related activity, and to be involved in movement preparation and execution, the relation between activity in these brain areas and the output of the brain onto the spinal cord remain elusive. Therefore, it is absolutely essential to characterize the contribution of upstream neural populations from other cortical and subcortical areas to the activity of the projection-specific populations of corticospinal neurons characterized in Project 1, during different modes of motor control. We propose to perform this characterization using a range of functional imaging approaches that interrogate this problem at different scales. We will utilize wide-field optical mapping (WFOM) to image, in an unbiased manner, the activity hundreds to thousands of cells across many cortical areas in relation to the activity of particular CSNs, which represent the output of the cortex to the spinal cord. Informed by the WFOM imaging, we will then perform simultaneous imaging of populations of neurons, with single cell resolution, in different brain areas using 2-photon random access mesoscopic (2p-RAM) imaging. Finally, we propose to use the 2pRAM mesoscope to simultaneously image the activity of thalamus or striatum through GRIN lenses, and the activity of corticospinal neurons, during particular motor control modes. The knowledge gained in this project will be critical to understand principles governing activity in motor cortex versus other cortical areas in relation to motor output as proposed in project 3, as well as to inform the modelling in project 4. Furthermore, it will help generate predictions that will be tested using closed-loop optogenetic manipulation experiments in project 5.