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Spinal circuits for mechanical itch and light touch

机械性瘙痒和轻触的脊髓回路

基本信息

批准号：
10624793
负责人：
Martyn D Goulding
金额：
$ 119.42万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2027-04-30
项目状态：
未结题

项目摘要

Animals and humans display a vast repertoire of behaviors, many of which are generated by motor networks in the spinal cord. This coordinated spinal motor activity is strongly regulated by descending motor control pathways and sensory afferent feedback. Sensory feedback is essential for both stereotypical protective reflexes, such as limb withdrawal, and for regulating ongoing motor behaviors, such as walking, running, and reaching. Interestingly, many descending motor control pathways converge on interneurons in the dorsal spinal cord that transmit sensory information, indicating a prominent role for these cells in motor control. Currently, very little is known about how sensorimotor networks in the spinal cord are organized at a cellular level. Efforts proposed here will use cutting-edge genetic manipulations and sensitive behavioral assays to deconstruct the cellular composition and synaptic connectivity of these sensorimotor circuits. The goals of this study are to functionally define the neuronal cell types that make up the sensorimotor circuitry and to generate a connectivity map that can then be used to construct a working model of how the sensorimotor circuitry is organized. Intersectional mouse genetics will be used to target specific populations of spinal neurons and ask whether inactivating or activating them with chemogenetic and optogenetic reporters perturbs specific sensorimotor pathways, including those that generate corrective behaviors during ongoing movement and noxious mechanical pathways that induce protective reflexes. Studies of protective and corrective reflexes will be complemented with an analysis of the sensory circuitry for the control of forelimb reaching and grasping behaviors. These studies, when completed, will provide new insights into the organization of the spinal reflex circuitry, and improve our understanding of the cellular computations that underlie sensorimotor transformation in the spinal cord.

动物和人类表现出大量的行为，其中许多是由运动产生的。脊髓中的神经网络。这种协调的脊髓运动活动受到下行运动的强烈调节。运动控制通路和感觉传入反馈。感官反馈对两者都至关重要刻板的保护性反射，如肢体退缩，以及用于调节正在进行的运动行为，比如走路、跑步和伸手。有趣的是，许多下行运动控制通路在脊髓背侧传递感觉信息的中间神经元上，这些细胞控制运动。目前，很少有人知道脊髓中的感觉运动网络脊髓是在细胞水平上组织起来的。这里提出的努力将使用尖端的基因操作和敏感的行为分析，以解构这些细胞的细胞组成和突触连接，感觉运动回路这项研究的目的是功能性地定义神经元细胞类型，建立感觉运动电路，并生成一个连接图，然后可以用来构建一个感觉运动回路是如何组织的将使用交叉小鼠遗传学以特定的脊髓神经元群体为目标，并询问是否用化学遗传学和光遗传学报道分子干扰特定的感觉运动通路，包括那些在进行中的运动和有害的机械途径，诱导产生纠正行为保护性反射对保护性和矫正性反射的研究将辅之以以下分析：控制前肢伸手和抓握行为的感觉回路。这些研究，当完成，将提供新的见解脊髓反射电路的组织，并提高我们的理解脊髓感觉运动转换的细胞计算。