Pectoralis Minor Activity in a Rodent Model of Respiratory Motor Neuron Loss
Authors: Borkowski Lauren F. , Nichols Nicole L. 
Published: April 2020

Patients with neuromuscular diseases experience loss of respiratory motor neurons (i.e., phrenic and intercostal) resulting in ventilatory failure, and ultimately death. No treatment is currently available to significantly prolong and/or improve breathing in these diseases. Since genetic rodent models of motor neuron loss develop global symptoms (e.g., dysphagia, limb paralysis, etc.), we have developed an inducible model of only respiratory motor neuron death in order to study how motor neuron loss impacts respiration and to develop therapeutic interventions. Briefly, adult rats are intrapleurally injected with cholera toxin B conjugated to saporin (CTB‐SAP) that is retrogradely transported to the phrenic and intercostal motor nuclei of the spinal cord, which results in selective elimination of phrenic and intercostal motor neurons. Despite deficits in maximal ventilatory capacity following CTB‐SAP, eupneic ventilation is maintained. Our preliminary data suggest that one way eupnea may be maintained in CTB‐SAP rats is via the recruitment of G‐coupled protein receptor‐dependent pathways to cause respiratory plasticity in the phrenic motor nucleus over the course of phrenic motor neuron death. However, our preliminary data also indicate that diaphragmatic amplitude appears to be decreased at baseline in CTB‐SAP rats vs. controls; thus, phrenic respiratory plasticity may only account for a portion of the maintenance of eupneic ventilation. We speculate that eupnea is also maintained through the recruitment of accessory inspiratory muscles (e.g., the pectoralis minor muscles) in the face of respiratory motor neuron loss. Pectoralis minor muscles are not normally utilized for eupnea, but have been shown to increase their activity to actively elevate the ribs upward and outward to move the chest wall following increased ventilatory demand (e.g., in response to disease or injury including spinal cord injury and bilateral diaphragmatic paralysis). Thus, we hypothesize that pectoralis minor activity is increased over the course of respiratory motor loss in CTB‐SAP rats vs. controls. To test our hypothesis, we are studying pectoralis minor output via electromyography in anesthetized, spontaneously breathing control and CTB‐SAP adult rats. Our preliminary data indicate that pectoralis minor activity appears to be increased in CTB‐SAP rats vs. controls (n=4/group). Thus, we conclude that the pectoralis minor muscles may also be recruited to maintain eupneic ventilation in the face of respiratory motor neuron death. Future studies will evaluate the recruitment of other accessory inspiratory muscles (e.g., scalenes, sternocleidomastoid, etc.) over the course of respiratory motor neuron loss, and whether these muscles (including the pectoralis minor) are necessary for eupnea in CTB‐SAP rats. This study furthers our understanding of the potential contribution accessory inspiratory muscles, specifically the pectoralis minor, have on the maintenance of eupneic ventilation following respiratory motor neuron loss. Lastly, if our hypothesis is correct, these muscles could potentially be further stimulated and harnessed to significantly prolong and/or improve breathing in patients with neuromuscular disease.

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Missouri Spinal Cord Injury/Disease Research Program