Characterizing the neural circuitry of postinspiratory behaviors and its coordination with breathing

项目总结

PROJECT SUMMARY Coordination of breathing with postinspiratory behaviors such as swallowing and laryngeal adduction is essential to health. Dysregulation of laryngeal activity during postinspiration and swallow occurs in many neurological and breathing-related disorders, such as obstructive sleep apnea, and can increase the risk of disordered swallow (dysphagia) and aspiration. Dysphagia is a major problem in patients with these diseases, and there are currently no treatments to cure or prevent dysphagia. This deficit is due in part to the lack of studies on coordination of breathing with laryngeal function of postinspiration and swallow. The recently described brainstem Postinspiratory Complex (PiCo) is thought to control postinspiration, yet its role in other laryngeal behaviors has not been studied. We test a fundamentally new hypothesis that excitatory medullary transmission from PiCo to the swallow pattern generator plays a role in swallow-related postinspiratory behavior. Our goals is to define the role of PiCo in postinspiratory laryngeal activity and swallow, and investigate potential coordination between the dorsal swallow group (DSG) and the ventral respiratory group (VRG). Based on preliminary data, we hypothesize that PiCo is a hub for both postinspiratory activity and swallowing, and has connections to the presumed swallow pattern generator in the nucleus tractus solitarius (nTS). We believe PiCo plays a role in swallow-related rhythmic activities which includes the nTS as the presumed swallow rhythm generator with projections to ventral respiratory centers. We use two in-vivo preparation: anesthetized and alert mouse combined with electrophysiology, novel optogenetics and Neuropixel recordings to test these hypotheses. We predict neural coordination of PiCo activity with respiratory and non-respiratory centers is similar between anesthetized and unanesthetized preparations. Investigating PiCo in an alert animal is important for characterizing the natural behaviors of swallow and laryngeal postinspiratory activity in a translational manner.