Synaptic Circuit Organization of Motor Cortex

描述（由申请人提供）：运动皮层（MC）作为皮层感觉运动网络中的主要节点发挥作用。携带从感觉/关联区到MC中的关键细胞类别（如皮质脊髓神经元）的长距离兴奋性投射的特定回路和突触机制尚未确定。关于皮层感觉处理的研究先前已经建立了从初级感觉到高级顶叶区的多个通路携带空间和非空间信息的概念，但是这些区域的兴奋性投射如何汇聚到皮层运动系统仍然知之甚少。在这里，我们提出了一个实验方案，旨在阐明细胞类型的特定连接的基础上，从顶叶皮层的高阶感觉/关联领域的远程皮质预测确定类MC神经元，专注于皮质脊髓神经元。我们将使用小鼠作为我们的实验模型，逆行和光遗传学标记，以及选择通路中功能性突触连接的靶向光生理记录来实现这一总体目标。我们的目的是：（1）确定压后皮质（RSC）向MC投射的突触结构。(2)将RSC的输入输出组织定义为MC的视觉-运动继电器。(3)确定到MC的S2输入的突触组织。(4)定义S2皮质脊髓神经元的输入输出组织。我们相信，拟议的研究计划是高度创新的，因为它汇集了强大的新技术，以解决一个重要的，但实验上以前无法访问的，在感觉运动研究领域的问题：特定的细胞机制介导的皮层通信从高阶感觉/关联区域运动皮层网络。拟议的研究是重要的，因为它将产生的宏观和微电路基础前馈皮质兴奋的特定类别的MC神经元的高阶感觉/关联领域参与感觉运动整合的基础知识。

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.