Respiratory motor control in the intact and injured spinal cord

呼吸障碍是颈髓损伤(SCI)的常见后果。这主要是因为 损伤控制呼吸肌的神经通路，包括主要肌肉--横隔肌 呼吸的影响。脊髓损伤后呼吸活动可以自发改善，但恢复的程度是 有限和严重的呼吸缺陷仍然存在。尽管做出了相当大的研究努力，但其机制 脊髓损伤后的呼吸恢复尚不清楚。在这里，我们将使用模块化组织的概念 运动控制以研究颈髓损伤大鼠完整的呼吸系统及其损伤和恢复。 电机控制的模块化组织是在几十年前提出的，主要是 开发的重点是运动系统。在这项工作中，我们将第一次研究模 自由行为大鼠颈脊髓损伤后呼吸控制的组织及其变化。一条C2脊髓 节段半横断(C2Hx)将作为脊髓损伤的模型。多发性肌电(EMG) 呼吸肌将被记录，并将使用独立成分分析(ICA)来识别一组 负责控制不同呼吸行为的模块。ICA将提取所展示的呼吸模块 通过神经模式(驱动原语)激活具有不同重量的呼吸肌肉组，称为 协同效应。呼吸是多种多样的，可以分为许多类型，包括休息和活动 在睡眠的不同阶段进行呼吸、挑战呼吸和呼吸。我们假设不同的是 呼吸类型是通过组合不同的模块来组织的。因此，拟议工作的目标是 以1)确定产生各种呼吸行为的基本呼吸模块及其排列 在完整的大鼠中；2)评估颈椎脊髓损伤后的模块变化；3)立即关联剩余的模块 脊髓损伤与自主恢复和持续性呼吸功能障碍的程度有关。 总体而言，这项极具创新性的研究将增加我们对健康组织的基本知识 颈椎脊髓损伤后呼吸系统的不同行为及其缺陷与恢复 电生理生物标志物用于预测损伤后呼吸恢复的程度。

Respiratory deficits are a common consequence of cervical spinal cord injury (SCI). This is primarily due to damage to the neural pathways controlling the respiratory muscles, including diaphragm – the primary muscle of respiration. Respiratory activity can spontaneously improve after SCI, however, the extent of recovery is limited and severe respiratory deficits persist. Despite considerable research efforts, the mechanisms of respiratory recovery post-SCI remain unknown. Here, we will use the concept of the modular organization of motor control to study the intact respiratory system and its deficits and recovery in cervical SCI rats. The modular organization of motor control was proposed several decades ago and had been mainly developed with a focus on the locomotor system. In this work, for the first time, we will study the modular organization of respiratory control and its changes after cervical SCI in freely behaving rats. A C2 spinal cord segment hemisection (C2Hx) will be employed as a model of SCI. Electromyograms (EMG) from multiple respiratory muscles will be recorded, and independent component analysis (ICA) will be used to identify a set of modules responsible for controlling different respiratory behaviors. ICA will extract respiratory modules presented by neural patterns (drive primitives) that activate groups of respiratory muscles with different weights, called synergies. Breathing is very heterogeneous and can be divided into many types, including resting and active breathing, challenged breathing, and breathing during different stages of sleep. We hypothesize that different types of breathing are organized by combining different modules. Therefore, the goals of the proposed work are to 1) identify those basic respiratory modules and their arrangements to produce various respiratory behaviors in intact rats; 2) evaluate modular changes after cervical SCI; 3) correlate remaining modules immediately after SCI with the extent of spontaneous recovery and lasting respiratory deficits. Overall, this highly innovative study will increase our basic knowledge about the organization of a healthy respiratory system during different behaviors, its deficits, and recovery after cervical SCI and help develop electrophysiological biomarkers to predict the extent of respiratory recovery post-injury.