Spinal circuits for mechanical itch and light touch

机械性瘙痒和轻触的脊髓回路

• 批准号: 9924686
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/9924686
• 关键词: Animals; Behavior; Behavioral Assay; Cells; Complement; Dorsal; Feedback; Forelimb; Goals; Human; Interneurons; Light; Limb structure; Maps; Mechanics; Modeling; Motor; Motor Activity; Movement; Neurons; Pathway interactions; Play; Population; Pruritus; Reflex action; Reporter; Role; Running; Sensory; Spinal; Spinal Cord; Spinal cord injury; Synapses; System; Touch sensation; Walking; Withdrawal; cell type; chronic itch; genetic manipulation; grasp; improved; insight; motor behavior; motor control; motor disorder; mouse genetics; novel strategies; optogenetics; painful neuropathy; sensory feedback; spinal reflex; transmission process

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