Carotid Bodies and the Integrated Cardiorespiratory Response to Hypoxia

Lindsey, Bruce G.; Nuding, Sarah C.; Segers, Lauren S.; Morris, Kendall F.

doi:10.1152/physiol.00014.2018

Cited by 29 publications

(25 citation statements)

References 265 publications

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“…Briefly, three main sensory stimuli that alert the brain during apnea are hypoxia, hypercapnia and negative air pressure in the airways created due to increased respiratory efforts (sensed by mechanoreceptor fibers in vagus) during apneas (White, 2006, 2017). The carotid body primarily senses the hypoxia and to a lesser extent the hypercapnia, and transmits that information to the nucleus of the solitary tract (NTS) via the carotid sinus branch of the glossopharyngeal nerve (Massari et al, 1996; Lindsey et al, 2018). In addition, the chemosensory neurons in the retrotrapezoid nucleus (RTN) directly sense the CO2, and these project in parallel to the NTS to the ventrolateral medulla (VLM- pattern generator for breathing), and parabrachial nucleus (PB- relay node for visceral sensory information from the brainstem to the forebrain) (Dean et al, 1989; Herbert et al, 1990; Finley and Katz, 1992; Massari et al, 1996; Guyenet et al, 2010a; Bochorishvili et al, 2012; Guyenet and Bayliss, 2015; Lindsey et al, 2018; Figure 1A).…”

Section: Introductionmentioning

confidence: 99%

Neural Circuitry Underlying Waking Up to Hypercapnia

Kaur

Saper

2019

Front. Neurosci.

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Obstructive sleep apnea is a sleep and breathing disorder, in which, patients suffer from cycles of atonia of airway dilator muscles during sleep, resulting in airway collapse, followed by brief arousals that help re-establish the airway patency. These repetitive arousals which can occur hundreds of times during the course of a night are the cause of the sleep-disruption, which in turn causes cognitive impairment as well as cardiovascular and metabolic morbidities. To prevent this potential outcome, it is important to target preventing the arousal from sleep while preserving or augmenting the increase in respiratory drive that reinitiates breathing, but will require understanding of the neural circuits that regulate the cortical and respiratory responses to apnea. The parabrachial nucleus (PB) is located in rostral pons. It receives chemosensory information from medullary nuclei that sense increase in CO2 (hypercapnia), decrease in O2 (hypoxia) and mechanosensory inputs from airway negative pressure during apneas. The PB area also exerts powerful control over cortical arousal and respiration, and therefore, is an excellent candidate for mediating the EEG arousal and restoration of the airway during sleep apneas. Using various genetic tools, we dissected the neuronal sub-types responsible for relaying the stimulus for cortical arousal to forebrain arousal circuits. The present review will focus on the circuitries that regulate waking-up from sleep in response to hypercapnia.

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Section: Introductionmentioning

confidence: 99%

Neural Circuitry Underlying Waking Up to Hypercapnia

Kaur

Saper

2019

Front. Neurosci.

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“…respiratory-sympathetic coupling under these conditions is a result of synchronized activation of respiratory and sympathetic medullar neurons (Zoccal, 2015;Lindsey et al, 2018). In the present study, the growth of CRC at rest in normobaric hypoxia in humans is shown for the first time, and the prevailing frequencies at which it occurs were highlighted.…”

Section: Discussionmentioning

confidence: 54%

“…It has been shown previously that acute hypoxia causes an increase in sympathetic activity and an increase in sympatho-respiratory coupling in rodents ( Dick et al, 2014 ). The enhanced respiratory-sympathetic coupling under these conditions is a result of synchronized activation of respiratory and sympathetic medullar neurons ( Zoccal, 2015 ; Lindsey et al, 2018 ). In the present study, the growth of CRC at rest in normobaric hypoxia in humans is shown for the first time, and the prevailing frequencies at which it occurs were highlighted.…”

Section: Discussionmentioning

confidence: 99%

Effect of Acute Hypoxia on Cardiorespiratory Coherence in Male Runners

et al. 2020

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Understanding the mechanisms of oxygen supply regulation, which involves the respiratory and cardiovascular systems, during human adaptation to intense physical activity, accompanied by hypoxemia, is important for the management of a training process. The objectives of this study were to investigate the cardiorespiratory coherence (CRC) changes in the low-frequency band in response to hypoxic exposure and to verify a dependence of these changes upon sports qualification level in athletes. Twenty male runners aged 17-25 years were exposed to acute normobaric hypoxia (10% O 2) for 10 min. Respiration, gas exchange, and heart rate were measured at baseline, during hypoxia, and after the exposure. To evaluate cardiorespiratory coupling, squared coherence was calculated based on 5-s averaged time series of heart and respiratory rhythms. Based on sports qualification level achieved over 4 years after the experimental testing, athletes were retrospectively divided into two groups, one high level (HLG, n = 10) and the other middle level (MLG, n = 10). No differences in anthropometric traits were observed between the groups. In the pooled group, acute hypoxia significantly increased CRC at frequencies 0.030-0.045 Hz and 0.075 Hz. In response to hypoxia, oxygen consumption decreased in HLG, and carbon dioxide production and ventilation increased in MLG. At 0.070-0.080 Hz frequencies in hypoxia, the CRC in HLG was higher than in MLG. Thus, highly qualified athletes enhance intersystem integration in response to hypoxia. This finding can be a physiological sign for the prognosis of qualification level in runners.

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“…The hypercapnia, hypoxia, and negative intrapharyngeal-airway pressure created by inspiratory effort against a blocked airway induce progressive activation of the GG. The Sol, PB, and ventrolateral medulla receive projections from chemosensory neurons in the retrotrapezoid nucleus, so they sense the hypercapnia, hypoxia, and other chemosensory information caused by apnea [44]. Our results indicated that all of these regions affect GG activity by innervating HMNs directly.…”

Section: Neural Circuitry Underlying Modulation Of Hmn Activity Durinmentioning

confidence: 67%

Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice

et al. 2020

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Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states. Identifying the neural mechanisms by which the statedependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep-wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs. Keywords Hypoglossal motor neuron Á Monosynaptic input Á Rabies virus Á Respiration Á Sleep and wake Han Guo and Xiang-Shan Yuan contributed equally to this work.

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Carotid Bodies and the Integrated Cardiorespiratory Response to Hypoxia

Cited by 29 publications

References 265 publications

Neural Circuitry Underlying Waking Up to Hypercapnia

Neural Circuitry Underlying Waking Up to Hypercapnia

Effect of Acute Hypoxia on Cardiorespiratory Coherence in Male Runners

Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice

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