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种独特的、重复的结构，这形成了一种特别有希望的 通过电刺激进行控制的目标。此外，这种结构允许基本电路用于 在脊髓损伤(SCI)水平以下应保留运动的产生。电刺激 因此，针对这些剩余感觉运动回路的技术正成为非常有希望的治疗方法。 这些入路通常利用脊柱解剖学的另一个基本方面，即所有感觉神经轴突 通过一个容易接近的位置进入脐带，即脐带的背部表面。因此，背部电刺激(DES)通过 表面电极可有效激活感觉神经轴突，而不需要穿透电极。 这些感觉轴突的脊椎连接对脊髓运动神经回路起着重要的调节作用。在这 提案中，我们研究了DES的神经机制，以清楚地确定其控制电机输出的潜力 并为改善其治疗实施创造合理的基础。DES的基本目标是 重建从大脑到脊髓的下行输入的关键功能，这些功能当然是受损或丧失的 在SCI中。因此，一个基本的问题是，感觉轴突的DES能否很好地复制 脊髓神经元的下行输入。为了解决这个问题，我们将重点放在正则电机微电路上。 (CMM)，它包括一组单一的拮抗剂运动池和处理其感觉的局部回路 关于肌肉长度和速度的反馈。传达这一信息的Ia组轴突很大，很可能 比任何其他类型的感官输入对DES更敏感。我们应用了多种技术，包括 感觉轴突内记录、中间神经元细胞外记录和电压钳 运动神经元。我们的目标是定位兴奋性和抑制性突触输入的分布。 通过DES的CMM，确定脊髓神经元的内在电特性在处理这些 输入，评估感觉轴突的DES激活是否干扰其正常功能，并探讨 当由DES或正常的感觉输入驱动时，作为CMM稳定性和焦点的基础的机制。 拟议的研究将为脊髓DES提供一个基本的基础，并有可能 寻找新的机会来提高其治疗效果。