Respiratory motor control in the intact and injured spinal cord

呼吸功能障碍是颈脊髓损伤 (SCI) 的常见后果。这主要是由于 控制呼吸肌的神经通路受损，包括膈肌（主要肌肉） 呼吸的。 SCI后呼吸活动可自发改善，但恢复程度有限 有限且严重的呼吸缺陷持续存在。尽管进行了大量的研究工作，但其机制 SCI 后的呼吸恢复情况仍不清楚。在这里，我们将使用模块化组织的概念 运动控制来研究颈椎 SCI 大鼠的完整呼吸系统及其缺陷和恢复。 电机控制的模块化组织是几十年前提出的，主要是 开发重点是运动系统。在这项工作中，我们将首次研究模块化 自由行为大鼠颈椎 SCI 后呼吸控制的组织及其变化。 C2脊髓 半节段（C2Hx）将被用作 SCI 的模型。多个肌电图 (EMG) 将记录呼吸肌，并使用独立成分分析（ICA）来识别一组 负责控制不同呼吸行为的模块。 ICA 将提取呈现的呼吸模块 通过神经模式（驱动原语）激活不同重量的呼吸肌群，称为 协同作用。呼吸非常不均匀，可以分为多种类型，包括静息呼吸和主动呼吸 呼吸、困难呼吸以及睡眠不同阶段的呼吸。我们假设不同 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 1）识别那些基本呼吸模块及其排列以产生各种呼吸行为 在完整的大鼠中； 2）评估颈椎SCI后的模块变化； 3) 立即关联剩余模块 SCI 具有自然恢复的程度和持续的呼吸缺陷。 总体而言，这项高度创新的研究将增加我们关于组织健康的基础知识。 不同行为期间的呼吸系统、其缺陷以及颈椎 SCI 后的恢复，并有助于发展 电生理生物标志物来预测受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.