Respiratory motor control in the intact and injured spinal cord

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.

Grant Number: 1R21NS131962-01A1
NIH Institute/Center: NIH
Principal Investigator: Tatiana Bezdudnaya