Synaptic Circuit Organization of Motor Cortex

运动皮层的突触电路组织

• 批准号: 8632022
• 负责人: Gordon M Shepherd
• 金额: $ 33.5万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632022
• 关键词: Address; Area; Axon; Behavior; Behavioral; Brain; Cells; Communication; Complex; Data; Disease; Dorsal; Epilepsy; Experimental Models; Goals; Health; Impairment; Knowledge; Label; Mediating; Mission; Modeling; Mono-S; Motor; Motor Cortex; Motor Pathways; Movement; Movement Disorders; Mus; National Institute of Neurological Disorders and Stroke; Nature; Neurons; Output; Paralysed; Parents; Parietal; Parietal Lobe; Pathology; Pathway interactions; Pattern; Physiological; Process; Property; Psyche structure; Public Health; Research; Sensory; Sensory Process; Side; Slice; Somatosensory Cortex; Specificity; Spinal; Stream; Synapses; System; Techniques; Testing; United States National Institutes of Health; Visual Cortex; Whole-Cell Recordings; Work; base; cell type; design; disability; frontal lobe; improved; in vivo; innovation; interest; motor control; nerve supply; neural circuit; neuropathology; novel; optogenetics; programs; public health relevance; response; somatosensory; voluntary movement disorder; way finding

PROJECT SUMMARY 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.

项目总结 运动皮质(MC)是皮质感觉运动网络中的一个主要节点。具体的电路和 突触机制携带从感觉/关联区到关键细胞的远程兴奋性投射 MC中的类别，如皮质脊髓神经元，尚未被鉴定。大脑皮层感觉的研究进展 处理之前已经建立了承载空间和非空间的多路径的概念 从初级感觉到高级顶叶区域的信息，但这些兴奋性投射是如何 皮质运动系统上汇聚的区域仍然知之甚少。在这里，我们建议进行一项实验 旨在阐明长期皮质投射背后的细胞类型特定连接性的程序 从顶叶皮质的高级感觉/关联区到已识别的MC神经元类别，重点是 皮质脊髓神经元。我们将使用鼠标作为我们的实验模型逆行来实现这一总体目标 和光遗传标记，以及有针对性的功能突触连接的光生理记录 小路。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)确定突触 组织向MC提供的S2输入。(4)确定S2皮质脊髓神经元的输入输出组织。这个 我们相信，拟议的研究项目具有很高的创新性，因为它汇集了强大的新技术 为了解决感觉运动学研究领域中一个重要的、但在实验上以前无法解决的问题： 从高级感觉/联想调节皮质通讯的特定细胞机制 运动皮质网络的区域。拟议的研究具有重要意义，因为它将产生 对特定类别皮质前馈兴奋的宏微电路基础的认识 参与感觉运动整合的高阶感觉/联想区对MC神经元的影响。