Mechanisms of electrical stimulation of a canonical motor microcircuit

典型电机微电路的电刺激机制

基本信息

批准号：
10468871
负责人：
Charles Heckman
金额：
$ 51.21万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2024-08-31
项目状态：
已结题

项目摘要

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.

脊髓的神经回路具有独特的重复结构，形成了特别有前途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要保留的运动生成以下脊髓损伤（SCI）的水平。电刺激因此，针对这些剩余的感觉运动电路的技术正成为高度有希望的疗法。这些方法通常利用脊柱解剖的另一个基本方面，所有感觉轴突通过高度可访问的位置进入绳索，其背面。因此，背刺激（DES）通过表面电极提供了无需穿透电极而无需穿透电极的感觉轴突的有效激活。这些感觉轴突的脊柱连接介导了对脊柱运动电路的有效作用。在这个提案，我们检查了DES的神经机制，以明确定义其控制电机输出的潜力并为改善其治疗性实施创建合理的基础。 DES的基本目标是重新创建从大脑到电线的下降输入的关键功能，当然是损坏或丢失的在科幻。因此，一个基本的问题是，感觉轴突的DES如何复制对脊柱神经元的输入下降。为了解决这个问题，我们专注于规范的电动机微电路（CMM），其中包括一组拮抗剂电机池和处理其感觉的本地电路有关肌肉长度和速度的反馈。传达此信息的IA组轴突很大，并且可能比其他任何类型的感觉输入更敏感。我们采用多种技术，包括感觉轴突中的轴内记录，中间神经元的细胞外记录和电压夹在运动神经元。我们的目的是绘制在该中产生的兴奋性和抑制性突触输入的分布 CMM由DES确定脊柱神经元在处理这些方面的内在电气特性的作用输入，评估感觉轴突的激活是否会干扰其正常功能并探测当DES或正常感觉输入驱动时，CMM的稳定性和焦点是基于CMM的机制。拟议的研究将为脊髓的DES提供基本的基础确定改善其治疗效果的新机会。