C1 neurons are part of the circuitry that recruits active expiration in response to peripheral chemoreceptors activation
Abstract
Breathing results from the interaction of three distinct oscillators: the pre-Bötzinger Complex (preBötC), driving inspiration, the post-inspiratory complex (PiCo), driving post-inspiration, and the lateral parafacial region (pFRG), driving active expiration. The pFRG is silent at rest and becomes rhythmically active during stimulation of peripheral chemoreceptors, which also activates adrenergic C1 cells. We postulated that the C1 cells and the pFRG may constitute functionally distinct but interacting populations for controlling expiratory activity during hypoxia. We found in rats that a) C1 neurons are activated by hypoxia and project to the pFRG region; b) active expiration elicited by hypoxia was blunted after blockade of ionotropic glutamatergic receptors at the level of the pFRG; and c) selective depletion of C1 neurons eliminated the active expiration elicited by hypoxia. These results suggest that C1 cells may regulate the respiratory cycle, including active expiration, under hypoxic conditions.
Data availability
All data generated or analyzed during this study are included in the manuscript
Article and author information
Author details
Funding
Fundação de Amparo à Pesquisa do Estado de São Paulo (Graduate Student Fellowship)
- Milene R Malheiros-Lima
Fundação de Amparo à Pesquisa do Estado de São Paulo (2016/23281-3)
- Ana C Takakura
Fundação de Amparo à Pesquisa do Estado de São Paulo (2015/23376-1)
- Thiago S Moreira
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance Code 001)
- Thiago S Moreira
Conselho Nacional de Desenvolvimento Científico e Tecnológico (301219/2016-8)
- Ana C Takakura
Conselho Nacional de Desenvolvimento Científico e Tecnológico (301904/2015-4)
- Thiago S Moreira
The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ronald L Calabrese, Emory University, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#07-2014) of the Institute of Biomedical Science of the University of São Paulo. All surgery was performed under anesthesia, and every effort was made to minimize suffering.
Version history
- Received: October 8, 2019
- Accepted: January 21, 2020
- Accepted Manuscript published: January 23, 2020 (version 1)
- Version of Record published: February 10, 2020 (version 2)
Copyright
© 2020, Malheiros-Lima 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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