Synaptic Circuit Organization of Motor Cortex

描述(申请人提供)：运动皮质(MC)在皮质感觉运动网络中起主要节点的作用。具体的回路和突触机制将长程兴奋性投射从感觉/关联区传递到MC中的关键细胞类别，如皮质脊髓神经元，目前尚不清楚。关于大脑皮层感觉加工的研究已经确立了多条通路将空间和非空间信息从初级感觉传递到高级顶区的概念，但这些来自这些区域的兴奋性投射如何汇聚到皮质运动系统仍然知之甚少。在这里，我们提出了一个实验方案，旨在阐明从顶叶皮质高级感觉/关联区到已识别类别的MC神经元的远程皮质投射背后的细胞类型特异性连接，重点是皮质脊髓神经元。我们将使用小鼠作为我们的实验模型来实现这一总体目标，逆行和光遗传标记，并在选定的路径中有针对性地记录功能性突触连接的光生理记录。我们的目标是：(1)确定脾后皮质(RSC)向MC投射的突触组织。(2)将RSC的输入输出组织定义为对MC的视觉马达接力。(3)确定S2传入MC的突触组织。(4)确定S2皮质脊髓神经元的输入输出组织。我们相信，拟议的研究计划具有很高的创新性，因为它结合了强大的新技术来解决感觉运动研究领域中一个重要的、但在实验上以前无法解决的问题：调节皮质通讯的特定细胞机制，从更高阶的感觉/关联区到运动皮质网络。这项研究具有重要意义，因为它将产生与感觉运动整合有关的高阶感觉/联系区域对特定类别MC神经元前馈皮质兴奋的宏微电路基础的基础知识。

DESCRIPTION (provided by applicant): The motor cortex (MC) functions as a major node in the cortical sensorimotor network. The specific circuits and synaptic mechanisms carrying long-range excitatory projections from sensory/association areas to key cell classes in MC such as corticospinal neurons have not yet been identified. Research on cortical sensory processing has previously established the concept of multiple pathways carrying spatial and non-spatial information from primary sensory to higher-order parietal areas, but how these excitatory projections from these areas converge on the cortical motor system remains poorly understood. Here we propose an experimental program designed to elucidate the cell-type specific connectivity underlying long-range corticocortical projections from higher-order sensory/association areas in parietal cortex to identified classes of MC neurons, focusing on corticospinal neurons. We will approach this overall goal using the mouse as our experimental model, retrograde and optogenetic labeling, and targeted opto-physiological recordings of functional synaptic connectivity in select pathways. Our aims are: (1) Determine the synaptic organization of retrosplenial cortex (RSC) projections to MC. (2) Define the input-output organization of RSC as a visuo-motor relay to MC. (3) Determine the synaptic organization of S2 inputs to MC. (4) Define the input-output organization of S2 corticospinal neurons. The proposed research program is highly innovative, we believe, because it brings together powerful new techniques to tackle an important, but experimentally previously inaccessible, issue in the field of sensorimotor research: the specific cellular mechanisms mediating corticocortical communication from higher-order sensory/association areas to motor cortical networks. The proposed research is significant because it will generate foundational knowledge about the macro- and microcircuit basis for feedforward corticocortical excitation of specific classes of MC neurons by higher-order sensory/association areas involved in sensorimotor integration.