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Respiratory motor control in the intact and injured spinal cord

$405,625R21FY2023NSNIH

Drexel University, Philadelphia PA

Investigators

Abstract

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.

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