The organization of spinal neurons following spinal cord injury

脊髓损伤后脊髓神经元的组织

• 批准号: 10340218
• 负责人: Christopher Keith Thompson
• 金额: $ 46.04万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-19 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10340218
• 关键词: Acute; Animal Model; Biological Markers; Brain Stem; Characteristics; Chronic; Clinical; Coupled; Data; Electrodes; Electrophysiology (science); Family Felidae; Future; Generations; Human; Individual; Injury; Interneurons; Knowledge; Lead; Lesion; Life Change Events; Measures; Mediating; Mental Depression; Microelectrodes; Modeling; Modification; Monitor; Motion; Motor; Motor Activity; Motor Neurons; Motor output; Movement; Muscle; Muscle Fibers; Nervous System Trauma; Neurons; Organizational Change; Outcome; Pathway interactions; Pattern; Pharmacology; Population; Preparation; Reflex action; Rehabilitation therapy; Sensory; Serotonin; Source; Spinal; Spinal Cord; Spinal Cord transection injury; Spinal cord injury; Statistical Models; Synapses; Synaptic plasticity; Testing; Ursidae Family; Work; advanced analytics; base; extracellular; genetic approach; improved; in vivo; innovation; insight; motor control; motor function improvement; neuroregulation; novel; novel strategies; public health relevance; receptive field; receptor; relating to nervous system; response; spinal shock; tool

Project Summary/Abstract Spinal cord injury (SCI) is a life-changing event that sets in motion profound alterations in motor output, sensory processing, and reflex activity. Immediately following injury there is a depression of motor activity mediated by a lack of descending drive. In the weeks and months following injury, a reorganization of spinal neurons (both motoneurons and interneurons) occurs in response to this altered milieu. This includes changes in the excitability and reorganization of remaining pathways through strengthening of latent connections and neuronal sprouting. SCI induced changes in the excitability of spinal motoneurons have a profound effect on their discharge characteristics and ultimately on the generation of muscle force for functional movements. The reorganization of spinal interneurons is less well understood, even though the overwhelming majority of synaptic drive to motoneurons is mediated by spinal interneurons. Therefore, this project will explore how spinal interneurons regulate the discharge of spinal motoneurons. We will combine intraspinal microelectrode arrays with arrays on the muscle to record the individual discharges of spinal interneuron and motor unit populations. On these data, we will bring to bear advanced statistical modeling to electrophysiology dissect the organization of spinal neurons through the quantification of the strength and directional effects of these excitatory/inhibitory connections. We will use this approach to quantify the organization of spinal neurons in the intact cord and following either chronic or acute SCI. Further, we will explore the effects of neuromodulation by targeting specific serotoninergic receptor subtypes. The expected outcome of this work is a new understanding of the function of the mammalian spinal cord and the capabilities for reorganization of spinal neurons following both chronic and acute spinal transections. This approach will be a platform for characterizing the synaptic input from spinal interneurons to motoneurons and how this ultimately produces movement. Our combined motor unit and interneuron approach will directly quantify the neural substrate underlying motor unit discharge patterns and will provide a strong basis for motor unit discharge patterns to be a detailed biomarker for quantifying the state of spinal interneurons in humans with SCI.

项目总结/摘要 脊髓损伤（SCI）是一种改变生活的事件，它会引起运动输出的深刻变化， 感觉处理和反射活动。受伤后，运动活动立即受到抑制 缺乏下行驱动力在受伤后的几周和几个月里， 神经元（运动神经元和中间神经元）响应于这种改变的环境而发生。这包括改变 通过加强潜在的联系， 神经元发芽脊髓损伤引起的脊髓运动神经元兴奋性的变化对脊髓损伤的发生有深远的影响。 它们的放电特性，并最终对功能性运动的肌肉力量的产生。的 脊髓中间神经元的重组还不太清楚，尽管绝大多数的神经元都是神经元。 对运动神经元的突触驱动由脊髓中间神经元介导。因此，本项目将探讨如何 脊髓中间神经元调节脊髓运动神经元的放电。我们将联合收割机 在肌肉上的阵列记录脊髓中间神经元和运动单位的单个放电 人口。在这些数据上，我们将运用先进的统计建模来分析电生理学。 组织脊髓神经元通过量化的强度和方向的影响，这些 兴奋性/抑制性连接。我们将使用这种方法来量化脊髓神经元的组织， 完整脊髓和慢性或急性SCI后。此外，我们将通过以下方式探索神经调节的效果： 靶向特定的肾上腺素能受体亚型。这项工作的预期成果是一种新的认识 哺乳动物脊髓的功能和脊髓神经元重组的能力， 慢性和急性脊髓横断。这种方法将是一个平台，用于表征突触 从脊髓中间神经元到运动神经元的输入以及这最终如何产生运动。我们的联合 运动单位和中间神经元方法将直接量化运动单位放电的神经基质 模式，并将为运动单位放电模式提供强有力的基础，作为详细的生物标志物， 量化SCI患者脊髓中间神经元的状态。