Abstract
Brainstem respiratory neuronal network significantly contributes to cough motor pattern generation. Neuronal populations in the pre-Bötzinger complex (PreBötC) represent a substantial component for respiratory rhythmogenesis. We studied the role of PreBötC neuronal excitation and inhibition on mechanically induced tracheobronchial cough in 15 spontaneously breathing, pentobarbital anesthetized adult cats (35 mg/kg, iv initially). Neuronal excitation by unilateral microinjection of glutamate analog d,l-homocysteic acid resulted in mild reduction of cough abdominal electromyogram (EMG) amplitudes and very limited temporal changes of cough compared with effects on breathing (very high respiratory rate, high amplitude inspiratory bursts with a short inspiratory phase, and tonic inspiratory motor component). Mean arterial blood pressure temporarily decreased. Blocking glutamate-related neuronal excitation by bilateral microinjections of nonspecific glutamate receptor antagonist kynurenic acid reduced cough inspiratory and expiratory EMG amplitude and shortened most cough temporal characteristics similarly to breathing temporal characteristics. Respiratory rate decreased and blood pressure temporarily increased. Limiting active neuronal inhibition by unilateral and bilateral microinjections of GABAA receptor antagonist gabazine resulted in lower cough number, reduced expiratory cough efforts, and prolongation of cough temporal features and breathing phases (with lower respiratory rate). The PreBötC is important for cough motor pattern generation. Excitatory glutamatergic neurotransmission in the PreBötC is involved in control of cough intensity and patterning. GABAA receptor-related inhibition in the PreBötC strongly affects breathing and coughing phase durations in the same manner, as well as cough expiratory efforts. In conclusion, differences in effects on cough and breathing are consistent with separate control of these behaviors.NEW & NOTEWORTHY This study is the first to explore the role of the inspiratory rhythm and pattern generator, the pre-Bötzinger complex (PreBötC), in cough motor pattern formation. In the PreBötC, excitatory glutamatergic neurotransmission affects cough intensity and patterning but not rhythm, and GABAA receptor-related inhibition affects coughing and breathing phase durations similarly to each other. Our data show that the PreBötC is important for cough motor pattern generation, but cough rhythmogenesis appears to be controlled elsewhere.
Highlights
Regulation of respiratory functions represents a complex interaction of chemodetection, generation of the respiratory rhythm, adjustments to various conditions and other competing behaviors, and effective control of spatiotemporal characteristics of the respiratory pattern
Data from neuronal recording experiments and modeling approaches strongly support the view that respiratory neurons in respiratory-related brainstem locations, including the PreBo€tC, form a common breathing/cough central pattern generator [9,10,11,12,13,14,15,16]
A frequent observation during studies that have used microinjection of neuroactive substances into areas that modulate the breathing pattern was differential effects on the breathing and cough motor patterns, which is explained by presumptive differing functions of respiratory neuronal assemblies when generating eupnea and cough. This process has been termed “reconfiguration.” The process of reconfiguration to generate the cough motor pattern when cough-related afferent inputs activate nucleus tractus solitarius (NTS), second-order neurons can include the recruitment of neurons that are silent during breathing but active during coughing, as well as changes in the phase and/or magnitude of major activation of spontaneously active of neurons in the network [9, 10, 25, 26]
Summary
Regulation of respiratory functions represents a complex interaction of chemodetection, generation of the respiratory rhythm, adjustments to various conditions and other competing behaviors, and effective control of spatiotemporal characteristics of the respiratory pattern. A frequent observation during studies that have used microinjection of neuroactive substances into areas that modulate the breathing pattern was differential effects on the breathing and cough motor patterns, which is explained by presumptive differing functions of respiratory neuronal assemblies when generating eupnea and cough This process has been termed “reconfiguration.” The process of reconfiguration to generate the cough motor pattern when cough-related afferent inputs activate nucleus tractus solitarius (NTS), second-order neurons can include the recruitment of neurons that are silent during breathing but active during coughing (behavior-specific), as well as changes in the phase and/or magnitude of major activation of spontaneously active of neurons in the network (retasking) [9, 10, 25, 26]
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