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.

动物和人类表现出广泛的行为曲目，其中许多是由电动机产生的脊髓中的网络。这种协调的脊柱运动活动受到下降的强烈调节电机控制途径和感觉传入反馈。感官反馈对于两者都是必不可少的刻板印象的防护反射，例如肢体拔出和调节持续的运动行为，例如步行，跑步和到达。有趣的是，许多下降的电动机控制途径汇聚关于传输感觉信息的背脊髓中的中间神经元，表明这些细胞在运动控制中。目前，关于脊柱中的感觉运动网络知之甚少脐带在细胞水平上组织。这里提出的努力将使用尖端的遗传操纵和对这些细胞组成和突触连通性的敏感行为测定感觉运动电路。这项研究的目标是在功能上定义使神经元细胞类型向上沿感觉运动电路并生成一个连接图，然后可以用于构造一个如何组织感觉运动电路的工作模型。将使用截切小鼠遗传学靶向特定的脊柱神经元群体，并询问是否会灭活或激活它们化学发生和光遗传学的报道者驱散特定的感觉运动途径，包括在正在进行的运动和有害的机械途径中产生纠正行为保护性反射。保护性和纠正反射的研究将通过对用于控制前肢和抓握行为的感觉电路。这些研究，什么时候完成，将为脊柱反射电路的组织提供新的见解，并改善我们的了解脊髓中感觉运动转化的基础的细胞计算。