C1 neurons are part of the circuitry that recruits active expiration in response to peripheral chemoreceptors activation

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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.

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All data generated or analyzed during this study are included in the manuscript

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Milene R Malheiros-Lima

Department of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil

Competing interests
The authors declare that no competing interests exist.
Josiane N Silva

Department of Pharmacology, University of São Paulo, São Paulo, Brazil

Competing interests
The authors declare that no competing interests exist.
Felipe C Souza

Department of Pharmacology, University of São Paulo, São Paulo, Brazil

Competing interests
The authors declare that no competing interests exist.
Ana C Takakura

Department of Pharmacology, University of São Paulo, São Paulo, Brazil

Competing interests
The authors declare that no competing interests exist.
Thiago S Moreira

Department of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil

For correspondence
tmoreira@icb.usp.br

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9789-8296

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.

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.

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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.