Abstract

The role of the cerebellum in controlling the cough motor pattern is not well understood. We hypothesized that cerebellectomy would disinhibit motor drive to respiratory muscles during cough. Cough was induced by mechanical stimulation of the tracheobronchial airways in anesthetized, spontaneously breathing adult cats (8 male, 1 female), and electromyograms (EMGs) were recorded from upper airway, chest wall, and abdominal respiratory muscles. Cough trials were performed before and at two time points after total cerebellectomy (10 minutes and >1 hour). Unlike a prior report in paralyzed, decerebrated, and artificially ventilated animals, we observed that cerebellectomy had no effect on cough frequency. After cerebellectomy, thoracic inspiratory muscle EMG magnitudes increased during cough (diaphragm EMG increased by 14% at 10 minutes, p = 0.04; parasternal by 34% at 10 minutes and by 32% at >1 hour, p = 0.001 and 0.03 respectively). During cough at 10 minutes after cerebellectomy, inspiratory esophageal pressure was increased by 44% (p = 0.004), thyroarytenoid (laryngeal adductor) muscle EMG amplitude increased 13% (p = 0.04), and no change was observed in the posterior cricoarytenoid (laryngeal abductor) EMG. Cough phase durations did not change. Blood pressure and heart rate were reduced after cerebellectomy, and respiratory rate also decreased due to an increase in duration of the expiratory phase of breathing. Changes in cough-related EMG magnitudes of respiratory muscles suggest that the cerebellum exerts inhibitory control of cough motor drive, but not cough number or phase timing in response to mechanical stimuli in this model early after cerebellectomy. However, results varied widely at >1 hour after cerebellectomy, with some animals exhibiting enhancement or suppression of one or more components of the cough motor behavior. These results suggest that, while the cerebellum and behavior-related sensory feedback regulate cough, it may be difficult to predict the nature of the modulation based on total cerebellectomy.

Highlights

  • Cough is vital to maintain a clear airway and a functional respiratory system

  • Anesthesia was initially induced with sevoflurane (4.5%), the animals were weaned onto sodium pentobarbital (25 mg/kg, i.v.)

  • Tracheal stimulation resulted in bouts of repetitive cough during control and following removal of the cerebellum, and a total of 280 coughs were analyzed

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Summary

Introduction

Cough is vital to maintain a clear airway and a functional respiratory system. It is elicited through mechanical and a variety of chemical stimuli applied to the airways including capsaicin and other TRPV1 agonists, acids, bradykinin, and histamine [1,2]. Aδ fibers transmit information related to punctate mechanical stimuli and acids, via the recurrent laryngeal and superior laryngeal branches of the vagus nerve, and terminate in the nucleus of the solitary tract (NTS), where they synapse on second-order interneurons [3,4]. These second order neurons synapse with various respiratory areas in the brainstem, including the ventral respiratory group, retrotrapezoid nucleus/parafacial respiratory group, midline raphe, nucleus ambiguus, and pontine respiratory group [5,6,7]. Xu and Frasier [18] demonstrated that electrical stimulation of the fastigial nucleus modulated respiratory phase timing, and that cerebellar ablation attenuated the hypoxic ventilatory response

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