Our research program is focused on understanding the role of respiratory afferents in cardiorespiratory control, the mechanisms by which afferents induce respiratory motor plasticity, and the therapeutic potential of respiratory afferent activation after cervical spinal cord injury. Our laboratory uses a multi-disciplinary approach including behavioral studies, neurophysiological preparations, and molecular techniques to investigate the functional significance and therapeutic potential of respiratory afferent activation, with the ultimate goal of identifying novel rehabilitative strategies to improve cardiorespiratory control following cervical spinal cord injury
Phrenic Afferents and Respiratory Motor Plasticity
Sensory input from the diaphragm can alter cardiorespiratory output. However, the impact of phrenic afferent activation on respiratory motor output over longer time scales remains largely unexplored. Our studies explore how repeated activation of phrenic afferents may induce long-lasting changes in phrenic motor output and the mechanisms underlying this plasticity.
Photo: Example of a phrenic afferent induced respiratory motor plasticity.
Phrenic Afferents and Spinal Cord Injury
Cervical spinal cord injury disrupts descending drive to the primary inspiratory muscle, the diaphragm, and results in profound breathing impairments. Individuals with cervical spinal cord injury are also at the highest risk for developing aberrant sympathetically driven cardiovascular responses. Respiratory afferents are known to influence both respiratory motor output and cardiovascular control. Our studies explore the therapeutic potential of respiratory afferent activation after cervical spinal cord injury.
Photo: An example of the recording equipment utilized with our chronic studies.
Chemogenetic Approaches to target Phrenic Afferents
Our work illustrates that phrenic afferents play an important role in the neural control of breathing and are important for recovery of breathing following spinal cord injury. We have developed addeno-associated viral (AAV) techniques to target phrenic afferents. We will utilizes these techniques to being chemogenetic studies in health and disease.
Photo: Photomicrograph of a dorsal root ganglion with Parvalbumin positive afferents (green) and AAV labeled phrenic afferents.
Reducing Inflammation after Spinal Cord Injury
In the initial hours-weeks after SCI, a cascade of inflammatory events is activated resulting in tissue damage, apoptosis, and formation of the glial scar which prevents axon regeneration. Our work in a non-scarring mammal, the African Spiny Mouse, has shown that reducing the inflammatory response reduces spinal scaring. We are investigating novel therapeutics to reduce inflammation and improve breathing following spinal cord injury.
Photo: Photomicrograph of Glial fibrillary acidic protein positive astrocytes after spinal cord injury.