Mechanisms of electrical stimulation of a canonical motor microcircuit

典型电机微电路的电刺激机制

• 批准号: 10247044
• 负责人: Charles Heckman
• 金额: $ 50.89万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247044
• 关键词: Address; Affect; Anatomy; Ankle; Axon; Behavior; Brain; Brain Stem; Databases; Dorsal; Effectiveness; Electric Stimulation; Electrodes; Felis catus; Frequencies; Generations; Goals; Interneurons; Length; Lesion; Limb structure; Location; Locomotion; Lumbar spinal cord structure; Maps; Mediating; Motor; Motor Neurons; Motor output; Movement; Muscle; Neurons; Neurostimulation procedures of spinal cord tissue; Norepinephrine; Pattern; Physiologic pulse; Posture; Preparation; Process; Property; Role; Sensory; Serotonin; Spinal; Spinal Cord; Spinal cord injury; Structure; Surface; Synapses; System; Techniques; Therapeutic; dorsal horn; electrical property; extracellular; improved; motor behavior; neural circuit; neuromechanism; preservation; presynaptic; response; restoration; sensory feedback; sensory input; success; synaptic inhibition; therapeutic effectiveness; voltage clamp

The neural circuitry of the spinal cord has a unique, repetitive structure that forms an especially promising target for control via electrical stimulation. Furthermore, this structure allows the essential circuits for generation of movements to be preserved below the level of a spinal cord injury (SCI). Electrical stimulation techniques targeted at these remaining sensorimotor circuits are thus becoming highly promising therapies. These approaches usually take advantage of another basic aspect of spinal anatomy, that all sensory axons enter the cord via a highly accessible location, its dorsal surface. Thus dorsal electrical stimulation (DES) via surface electrodes provides effective activation of sensory axons without the need for penetrating electrodes. The spinal connections of these sensory axons mediate potent effects on spinal motor circuits. In this proposal, we examine the neural mechanisms of DES to clearly define its potential for controlling motor output and to create a rational basis for improving its therapeutic implementation. The basic goal of DES is to recreate key functions of the descending inputs from the brain to the cord, which are of course damaged or lost in SCI. Thus a fundamental question is, how well can DES of sensory axons replicate the effects of descending inputs on spinal neurons. To address this question, we focus on the canonical motor microcircuit (CMM), which comprises a single set of antagonist motor pools and the local circuits that process their sensory feedback about muscle length and velocity. The group Ia axons conveying this information are large and likely to be more sensitive to DES than any other type of sensory input. We apply multiple techniques, including intra-axonal recording in sensory axons, extracellular recording of interneurons and voltage clamp in motoneurons. Our Aims are to map the distribution of excitatory and inhibitory synaptic input generated in the CMM by DES, identify the roles of the intrinsic electrical properties of spinal neurons in processing these inputs, assess whether DES activation of sensory axons interferes with their normal function and probe the mechanism that underlie the stability and focus of the CMM when driven by DES or normal sensory inputs. The proposed studies will provide a fundamental underpinning for DES of the spinal cord and are likely to identify new opportunities for improvement its therapeutic effectiveness.

脊髓的神经回路有一个独特的，重复的结构，形成了一个特别有希望的