Synaptic Circuit Organization of Motor Cortex

描述（由申请人提供）：运动皮层（MC）是皮层感觉运动网络的主要节点。从感觉/关联区到MC中的关键细胞类别（如皮质脊髓神经元）的远程兴奋性投射的特定电路和突触机制尚未确定。皮层感觉加工的研究已经建立了从初级感觉区到高阶顶叶区携带空间和非空间信息的多条通路的概念，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程序，旨在阐明从顶叶皮层的高阶感觉/关联区到已识别的MC神经元类别的远程皮质皮质投射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，逆行和光遗传学标记，并在选择的途径中有针对性地记录功能性突触连接的光生理记录，来实现这一总体目标。我们的目标是：(1)确定脾后皮层（RSC）投射到MC的突触组织(2)确定RSC的输入-输出组织作为MC的视觉-运动继电器(3)确定S2输入到MC的突触组织(4)确定S2皮质脊髓神经元的输入-输出组织。我们认为，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来解决一个重要的，但在实验上以前无法达到的感觉运动研究领域的问题：从高阶感觉/关联区域到运动皮质网络的皮质-皮质通讯的特定细胞机制。这项研究具有重要意义，因为它将为涉及感觉运动整合的高阶感觉/关联区域对特定类别的MC神经元的前馈皮质-皮质兴奋的宏观和微电路基础提供基础知识。

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.