PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate
Abstract
Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, with respiratory neurons entraining the activity of pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory oscillations. The findings have implications for cardiovascular pathologies, such as hypertension and heart failure, where respiratory entrainment of heart rate is diminished and respiratory entrainment of blood pressure exaggerated.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data and statistics files have been provided for Figures 2, 3, 4, 5, 6, 7 and 8.
Article and author information
Author details
Funding
National Health and Medical Research Council (App #1120477)
- Clément Menuet
- Simon McMullan
- Andrew M Allen
National Health and Medical Research Council (App #1156727)
- Clément Menuet
- Simon McMullan
- Andrew M Allen
Australian Research Council (DP120100920)
- Simon McMullan
- Andrew M Allen
Australian Research Council (DP170104582)
- Andrew M Allen
University of Melbourne (-McKenzie Research Fellowship)
- Clément Menuet
Fondation pour la Recherche Médicale (Fellowship ARF20160936221)
- Clément Menuet
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Muriel Thoby-Brisson, CNRS Université de Bordeaux, France
Ethics
Animal experimentation: Experiments were conducted in accordance with the Australian National Health and Medical Research Council 'Code of Practice for the Care and Use of Animals for Scientific Purposes' and were approved by the University of Melbourne Animal Research Ethics and Biosafety Committees (ethics ID #1413273, #1614009, #1814599 and Florey 16-040).
Version history
- Received: March 26, 2020
- Accepted: June 14, 2020
- Accepted Manuscript published: June 15, 2020 (version 1)
- Version of Record published: June 30, 2020 (version 2)
Copyright
© 2020, Menuet et al.
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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