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

表征与皮质脊髓输出和运动控制相关的长程皮质和皮质下动力学

• 批准号: 9983207
• 负责人: Elizabeth M. C. Hillman
• 金额: $ 49.16万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9983207
• 关键词: Animals; Area; Basal Ganglia; Behavior; Behavior monitoring; Bilateral; Brain; Calcium; Cells; Chronic; Color; Corpus striatum structure; Data; Dorsal; Extensor; Flexor; Forelimb; Functional Imaging; Grooming; Head; Image; Knowledge; Label; Maps; Methods; Microscopy; Modeling; Monitor; Motor; Motor Activity; Motor Cortex; Motor output; Movement; Mus; Muscle; Neurofibrillary Tangles; Neurons; Optics; Output; Pattern; Performance; Population; Population Projection; Preparation; Property; Resolution; Rest; Speed; Spinal Cord; Surface; Surveys; System; Task Performances; Testing; Thalamic structure; Thinness; Validation; Volition; Work; awake; base; cell type; cranium; experimental study; hemodynamics; imaging approach; imaging modality; lens; motor control; optogenetics; relating to nervous system; two photon microscopy; two-photon

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.

抽象的 即使是简单的运动，例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被证明具有与运动相关的活动，并且 参与运动准备和执行的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，确定其特征是绝对必要的 来自其他皮质和皮质下区域的上游神经群对大脑活动的贡献 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 电机控制。我们建议使用一系列功能成像方法来执行此表征，这些方法 在不同的尺度上审视这个问题。我们将利用宽视场光学映射 (WFOM) 进行成像 以公正的方式，许多皮层区域的数百至数千个细胞的活动与 特定 CSN 的活动，代表皮质到脊髓的输出。 根据 WFOM 成像的信息，我们将对神经元群进行同步成像， 使用 2 光子随机存取介观 (2p-RAM) 成像在不同大脑区域获得单细胞分辨率。 最后，我们建议使用 2pRAM 介观镜同时对丘脑或纹状体的活动进行成像 在特定的运动控制模式下，通过 GRIN 透镜以及皮质脊髓神经元的活动。 在这个项目中获得的知识对于理解运动皮层活动的控制原理至关重要 与项目 3 中提出的与运动输出相关的其他皮质区域相比，并告知 项目 4 中的建模。此外，它将有助于生成将使用闭环进行测试的预测 项目5中的光遗传学操纵实验。