Spinal circuits for mechanical itch and light touch

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。感觉反馈对这两个人都是必不可少的 陈旧的保护性反射，如肢体收回，以及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汇聚在一起 在脊髓背侧传递感觉信息的中间神经元上，表明 这些细胞处于运动控制中。目前，人们对脊髓中的感觉运动网络知之甚少 绳索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 以及敏感的行为分析，以解构这些细胞的组成和突触连接 感应器运动电路。这项研究的目标是从功能上定义使 并生成连接图，该图随后可用于构建 感应器电机电路如何组织的工作模型。将使用交叉小鼠遗传学 以特定群体的脊髓神经元为目标，询问是用灭活还是用激活 化学发生和光遗传记者扰乱特定的感觉运动通路，包括那些 在持续运动和有害的机械路径中产生纠正行为，从而导致 保护性反射。对保护性和矫正性反射的研究将补充对 控制前肢伸展和抓握行为的感觉回路。这些研究，当 完成后，将为脊椎反射回路的组织提供新的见解，并改进我们的 理解脊髓感觉运动转换背后的细胞计算。

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.