Postnatal changes in O2 and CO2 sensitivity in rodents

https://doi.org/10.1016/j.resp.2019.103313Get rights and content

Highlights

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    The respiratory control system of rodents undergoes dynamic postnatal changes.

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    Changes in peripheral and central chemoreceptors shape ventilatory development.

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    Postnatal changes of the respiratory control system are not uniform in all rodents.

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    A fossorial lifestyle affects the development of O2 and CO2 sensitivity in rodents.

Abstract

In rodents, the ventilatory responses to hypoxia (low O2) and hypercarbia (high CO2) change significantly over postnatal development. In hypoxia, most adult rodents increase ventilation and decrease metabolism to some degree. Hypercarbia, however, leads to an increase in ventilation with little, to no change in metabolism. Neonates, on the other hand, respond to hypoxia with a profound metabolic depression, and a severely attenuated ventilatory response. In hypercarbia, they exhibit a strong ventilatory response early in development that blunts, reaches a nadir, and then rises back to the adult-like response, thus, stabilizing postnatally. In this review we discuss how the O2 and CO2 ventilatory responses develop in rodents, the possible mechanisms that drive these postnatal changes, and how being raised in a burrow, an environment putatively low in O2 and high in CO2, may affect the development of O2 and CO2 sensitivity in rodents.

Introduction

During the first three weeks of postnatal development, rodentsundergo dynamic changes in respiratory control that coincide with distinct anatomical, morphological, neurochemical and metabolic changes (for a review see Fong, 2010; Putnam et al., 2005; Wong-Riley et al., 2013, 2019). These postnatal changes in respiratory control underlie observed changes in the ventilatory responses to hypoxia and hypercarbia, and shape maturational changes in O2 and CO2 sensitivity. In this brief review we discuss the factors contributing to the postnatal changes in O2 and CO2 sensitivity, starting with changes in the morphology and function of the chemoreceptors and the process of chemotransduction through development. We then describe new information detailing how this translates into changes in the respiratory pattern, the coupling of ventilation to metabolism, and the effects of the respiratory gases and temperature on this coupling through postnatal development. Lastly, we discuss the set-point and the sensitivity of the respiratory control system in response to changing levels of O2 and CO2.We conclude with a new overview of development of chemosensitivity in rodents raised in burrows, where ambient O2 levels may be chronically low, and CO2 levels high. We note that although there has been tremendous progress towards our understanding of the postnatal changes in O2 and CO2 sensitivity in rodents, a considerable amount of work remains to be done, presenting novel and exciting opportunities for future studies.

Section snippets

Peripheral arterial chemoreception

In mammals, peripheral arterial chemoreceptors are found mainly in the carotid and aortic bodies (Heymans and Neil, 1958; Lahiri and Forster, 2003; Nurse, 2014; O’Regan and Majcherczyk, 1982). Both the carotid and aortic bodies respond to changes in arterial blood O2 and CO2 levels, although the primary stimulus for both is a fall in O2. While both the carotid and aortic bodies sense changes in arterial O2 partial pressure, the aortic bodies are also sensitive to changes in arterial blood O2

Postnatal development of respiratory pattern: respiratory frequency versus tidal volume

Changes in total ventilation are mediated by adjustments in respiratory frequency and tidal volume, and reflect the balance of multiple inputs acting on the central rhythm generators that set the frequency and amplitude of the inspiratory and expiratory motor output (Wyman, 1997). These inputs originate from peripheral and central chemoreceptors, as well as pulmonary stretch receptors in the lungs, and descending input from the pontine group within the brainstem (Bianchi et al., 1995;

Effects of cold

Ambient temperature can play a pervasive role in the coupling of metabolism and ventilation (for a review see Mortola and Maskrey, 2011). When ambient temperature plummets, adult mammals elicit a thermogenic response in order to maintain a constant body temperature, resulting in a significant increase in their metabolism. This increase in O2 requirement is accompanied by a proportional increase in ventilation (Barros et al., 2001; Dupré et al., 1988; Dzal and Milsom, 2019; Hill, 1959; Saiki and

Postnatal development of ventilatory drive: O2 and CO2 sensitivity and set-point

Ventilatory sensitivity is defined as the magnitude of the ventilatory response for any given change in O2 or CO2 tension, and is indicated by the slope of ventilatory output for any given change in O2 or CO2 partial pressure (Duffin and Mahamed, 2003). The ventilatory set-point, or threshold, is the O2 or CO2 tension of the blood required to generate an increase in ventilatory drive (Duffin and Mahamed, 2003). This threshold must be met before a ventilatory response is produced. Because of the

Growing up in a low O2, high CO2 home: fossoriality and development

Throughout this review we have highlighted the postnatal changes that occur in the respiratory control system of rodents. Our discussion has been comparatively limited due to the paucity of studies on rodents other than the rat. Most of these studies were performed on laboratory bred commercial strains. These animals develop, reproduce, and live in normoxic and normocarbic conditions. Thus, they are not faced with the low levels of O2, and high levels of CO2 often present in a burrow (Tenney

Acknowledgments

This work was funded by NSERC of Canada (NSERC 22R87150). The authors would also like to thank Nicha Boonpattrawong for discussion and comments on earlier versions of this review.

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    1

    Present address: Department of Biology and Centre for Forest Interdisciplinary Research, University of Winnipeg, 515 Portage Ave., Winnipeg, MB, R3B 2E9, Canada.

    2

    Equal contribution.

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