PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate

Author:

Menuet Clément12ORCID,Connelly Angela A1,Bassi Jaspreet K1,Melo Mariana R1,Le Sheng3,Kamar Jessica1,Kumar Natasha N4,McDougall Stuart J5ORCID,McMullan Simon3,Allen Andrew M15ORCID

Affiliation:

1. Department of Physiology, University of Melbourne, Victoria, Australia

2. Institut de Neurobiologie de la Méditerranée, INMED UMR1249, INSERM, Aix-Marseille Université, Marseille, France

3. Faculty of Medicine & Health Sciences, Macquarie University, NSW, Australia

4. Department of Pharmacology, School of Medical Sciences, University of New South Wales, NSW, Australia

5. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia

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.

Funder

National Health and Medical Research Council

Australian Research Council

University of Melbourne

Fondation pour la Recherche Médicale

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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