Phase synchronization as a flexible definition of the respiratory pattern: Application to pontine‐dependent control of the respiratory pattern

Abstract

A distinct pattern of inspiratory, post‐inspiratory and expiratory activities that are expressed in respiratory‐modulated neurons and motor outputs during stationary breathing are the foundation of most contemporary models for respiratory rhythm generation and pattern formation. Models and experiments show that impaired synaptic inhibition in the respiratory circuitry of the brainstem is associated with neurogenic breathing disorders in Rett syndrome (inspiratory efforts against a closed glottis) or with paradoxical vocal cord movement (glottal closure during inspiration). Previously, we reported that the pontine Kölliker‐Fuse nuclei (KFn) couple the spinal and cranial motor patterns and control respiratory pattern variability. Here, we test the hypothesis that the KFn is critical for expression of the phase relationships among respiratory motor activities. In arterially‐perfused brainstem preparations (n=7), we recorded respiratory activity from the hypoglossal, cervical vagal, phrenic and iliohypogastric nerves before and after bilateral bicuculline (a GABA(A)R antagonist, 50nl, 10mM) microinjections in the KFn. Disinhibition of KFn increased the variability of the respiratory rhythm (coefficient of variation (CV) of cycle duration (TTOT before, 0.10 ± 0.01 versus after bicuculline 0.50 ± 0.26, p<0.01). The increase in variability was associated with unpredictable timing of phase durations and transitions. Standard metrics such as TTOT failed to quantitatively describe the complexity in the changes of the respiratory motor pattern. Here, we introduce a quantitative definition of the respiratory motor pattern based on the phase synchronization of respiratory motor outputs or its underlying neuronal activities. Power spectral analysis revealed that the respiratory motor activities had a periodicity indicating that a coherent respiratory‐pattern persisted. Quantifying phase synchronization of respiratory motor outputs revealed a significant reduction in coupling strengths, without a change in their relative phase relationships (mean relative phase at baseline, 1.16 ± 0.07 rad versus after disinhibition, 1.17 ± 0.05 rad; and phase coherence at baseline, 0.87 ± 0.01 versus after disinhibition, 0.31 ± 0.03, p=3.68×10−4). Our data further support the concept that respiratory pattern formation requires reciprocal interaction between pontine and medullary respiratory groups. Focal pontine disinhibition resulted in reduced coupling strength between ponto‐medullary synaptic interactions that consequently disrupted the motor pattern, while the undisturbed medullary aspects are able to uphold the periodicity of respiration. Taken together, our results illustrate that medullary respiratory rhythm generating circuit require the pons to convert its periodicity into a viable and vital respiratory motor pattern.Support or Funding InformationSupported by a grant from the Australian Research Council.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.