Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P
Abstract
The rhythm generating network for breathing must continuously adjust to changing metabolic and behavioral demands. Here, we examined network-based mechanisms in the mouse preBӧtzinger complex using substance P, a potent excitatory modulator of breathing frequency and stability, as a tool to dissect network properties that underlie dynamic breathing. We find that substance P does not alter the balance of excitation and inhibition during breaths or the duration of the resulting refractory period. Instead, mechanisms of recurrent excitation between breaths are enhanced such that the rate that excitation percolates through the network is increased. We propose a conceptual framework in which three distinct phases of inspiration, the burst phase, refractory phase, and percolation phase, can be differentially modulated to control breathing dynamics and stability. Unraveling mechanisms that support this dynamic control may improve our understanding of nervous system disorders that destabilize breathing, many of which involve changes in brainstem neuromodulatory systems.
Data availability
All data generated during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.
Article and author information
Author details
Funding
National Heart, Lung, and Blood Institute (R01 HL126523)
- Jan-Marino Ramirez
National Heart, Lung, and Blood Institute (R01 HL144801)
- Jan-Marino Ramirez
National Heart, Lung, and Blood Institute (K99 HL145004)
- Nathan A Baertsch
National Heart, Lung, and Blood Institute (F32 HL134207)
- Nathan A Baertsch
National Heart, Lung, and Blood Institute (P01 HL090554)
- Jan-Marino Ramirez
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments and animal procedures were approved by the Seattle Children's Research Institute's Animal Care and Use Committee and conducted in accordance with the National Institutes of Health guidelines. (approved protocol #15981)
Copyright
© 2019, Baertsch & Ramirez
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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