Regulation of Breathing and Autonomic Outflows by Chemoreceptors

Guyenet, Patrice G.

doi:10.1002/cphy.c140004

Cited by 261 publications

(317 citation statements)

References 468 publications

Supporting

Mentioning

293

Contrasting

Unclassified

Order By: Relevance

“…Given that AMPK deletion blocked the HVR, this may appear contrary to the view that increased afferent discharge from the carotid body to the brainstem determines the ventilatory response to a fall in arterial PO 2 (12). However, evidence suggests that the HVR is determined by the coordinated action of the carotid body and a hypoxiaresponsive circuit within the brainstem (26) comprising, in great part, TH-expressing catecholaminergic cells (14,15).…”

Section: Discussionmentioning

confidence: 87%

“…Therefore, AMPK deletion selectively blocks the HVR and thus precipitates hypoventilation and apnea. Furthermore, because hypercapnic ventilatory drive is retained in these mice and is delivered by CO 2 -and/or pHsensitive catecholaminergic neurons (14,23), it is evident that AMPK deletion does not simply block neuronal activation or synaptic transmission per se (see also below, AMPK IS NOT REQUIRED FOR CAROTID BODY ACTIVATION BY HYPOXIA).…”

Section: Loss Of Ampk Leads To Ventilatory Dysfunction During Hypoxiamentioning

confidence: 99%

“…These semiautonomous neural networks comprise core circuits of excitatory and inhibitory interneurons that deliver rhythmic patterns of activity (10) and confer a set point about which respiratory rhythm is continuously modulated through the integration of inputs from those central (10,11) and peripheral (12) chemosensors that monitor O 2 , CO 2 , and pH. It is generally accepted that the carotid bodies represent the primary arterial chemoreceptors (12) and that the acute hypoxic ventilatory response (HVR) is delivered by increased afferent discharge from the carotid bodies to the rCPGs via, in great part, catecholaminergic networks within the caudal brainstem (13,14).…”

mentioning

confidence: 99%

See 2 more Smart Citations

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

Mahmoud¹,

Lewis²,

Juričić³

et al. 2016

Am J Respir Crit Care Med

104

View full text Add to dashboard Cite

Rationale: Modulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep and ascent to altitude, but the precise molecular mechanisms of this phenomenon remain controversial. Among the genes influenced by natural selection in high-altitude populations is one for the adenosine monophosphate-activated protein kinase (AMPK) a1-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress.Objectives: We investigated whether AMPK-a1 and/or AMPK-a2 are required for the hypoxic ventilatory response and the mechanism of ventilatory dysfunctions arising from AMPK deficiency.Methods: We used plethysmography, electrophysiology, functional magnetic resonance imaging, and immediate early gene (c-fos) expression to assess the hypoxic ventilatory response of mice with conditional deletion of the AMPK-a1 and/or AMPK-a2 genes in catecholaminergic cells, which compose the hypoxia-responsive respiratory network from carotid body to brainstem.Measurements and Main Results: AMPK-a1 and AMPK-a2 deletion virtually abolished the hypoxic ventilatory response, and ventilatory depression during hypoxia was exacerbated under anesthesia. Rather than hyperventilating, mice lacking AMPK-a1 and AMPK-a2 exhibited hypoventilation and apnea during hypoxia, with the primary precipitant being loss of AMPK-a1 expression. However, the carotid bodies of AMPK-knockout mice remained exquisitely sensitive to hypoxia, contrary to the view that the hypoxic ventilatory response is determined solely by increased carotid body afferent input to the brainstem. Regardless, functional magnetic resonance imaging and c-fos expression revealed reduced activation by hypoxia of well-defined dorsal and ventral brainstem nuclei.Conclusions: AMPK is required to coordinate the activation by hypoxia of brainstem respiratory networks, and deficiencies in AMPK expression precipitate hypoventilation and apnea, even when carotid body afferent input is normal.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Loss Of Ampk Leads To Ventilatory Dysfunction During Hypoxiamentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

Mahmoud¹,

Lewis²,

Juričić³

et al. 2016

Am J Respir Crit Care Med

104

View full text Add to dashboard Cite

show abstract

“…Evidence suggests there is a definitive link between the sympathetic nerve and breathing [51] [52]; therefore, we contend that more research should focus on the link between respiration and sub-threshold oscillations in various organs.…”

Section: Breathing Brings Consciousness To Lifementioning

confidence: 99%

The Dynamic Role of Breathing and Cellular Membrane Potentials in the Experience of Consciousness

Jerath¹,

Cearley²,

Barnes³

et al. 2017

WJNS

View full text Add to dashboard Cite

Understanding the mechanics of consciousness remains one of the most important challenges in modern cognitive science. One key step toward understanding consciousness is to associate unconscious physiological processes with subjective experiences of sensory, motor, and emotional contents. This article explores the role of various cellular membrane potential differences and how they give rise to the dynamic infrastructure of conscious experience. This article explains that consciousness is a body-wide, biological process not limited to individual organs because the mind and body are unified as one entity; therefore, no single location of consciousness can be pinpointed. Consciousness exists throughout the entire body, and unified consciousness is experienced and maintained through dynamic repolarization during inhalation and expiration. Extant knowledge is reviewed to provide insight into how differences in cellular membrane potential play a vital role in the triggering of neural and non-neural oscillations. The role of dynamic cellular membrane potentials in the activity of the central nervous system, peripheral nervous system, cardiorespiratory system, and various other tissues (such as muscles and sensory organs) in the physiology of consciousness is also explored. Inspiration and expiration are accompanied by oscillating membrane potentials throughout all cells and play a vital role in subconscious human perception of feelings and states of mind. In addition, the role of the brainstem, hypothalamus, and complete nervous system (central, peripheral, and autonomic) within the mind-body space combine to allow consciousness to emerge and to come alive. This concept departs from the notion that the brain is the only organ that gives rise to consciousness.

show abstract

“…The retrotrapezoid nucleus (RTN) is postulated as a primary CRC and responsible for fine control of PaCO 2 stabilization (Guyenet, 2014b). The effects of the CRCs, specifically the RTN, influence breathing through sensing pH, integrating salient information and projecting to brain regions responsible for creating the respiratory rhythm.…”

mentioning

confidence: 99%

Neural Control of Respiration by the Retrotrapezoid Nucleus.

Basting¹

View full text Add to dashboard Cite

Rationale and objectives: Central respiratory chemoreceptors (CRCs) detect brain PaCO 2 and adjust lung ventilation to maintain PaCO 2 and pH constant regardless of the absolute level of lung ventilation. They perform this function in cooperation with the carotid bodies, sensory organs that respond to hypoxia in a pH-dependent manner. The existence of CRCs has been known for over a century but their cellular nature and location have remained highly controversial until recently. The retrotrapezoid nucleus (RTN), a collection of ~2000 glutamatergic neurons in rats that are activated by hypercapnia in vivo and by acidification in slices, had been identified as a CRC candidate just prior to my PhD work. My first objective was to seek additional and critical evidence that RTN neurons are CRCs by determining whether these neurons stimulate breathing in proportion to arterial PCO 2 in intact unanesthetized rats.Having verified that this was the case I tested a logical corollary of this theory namely that RTN is silenced under hypoxic conditions due to respiratory alkalosis. Then I proceeded to test whether RTN neurons sustain breathing automaticity during sleep. Finally, I tested whether RTN compensates for the lack peripheral chemoreceptor input.Methods: RTN neurons were bilaterally transduced to express the proton pump archaerhodopsin using a lentiviral vector. Using anesthetized rats, I confirmed that RTN neurons were silenced by activating archaerhodopsin with green light. I examined the effect of short periods of RTN inhibition (10s) on breathing (plethysmography), EEG and neck EMG in conscious rats in which arterial pH was changed by exposing the animals to various FiO 2 levels alone or with the addition of 3% FiCO 2 or acetazolamide (ACTZ). Rats were studied in different states of vigilance (quiet awake/non-REM/REM). Arterial blood gases (PaO 2 , PaCO 2 ), pHa and HCO 3 were measured under each condition.ii Results: RTN inhibition (bilateral) reduced breathing frequency and amplitude in direct proportion to arterial plasma pH (pHa) below a threshold of 7.53. Above this level, RTN inhibition had no effect suggesting that the nucleus was silent. In normoxia, RTN inhibition reduced breathing equally during non-REM sleep and quiet wake. By contrast RTN inhibition had very little effect on breathing during REM sleep.Conclusions: RTN drives breathing in direct proportion to arterial PCO 2 in intact unaesthetized rats, consistent with the theory that these neurons are CRCs. RTN neurons are silent above pHa 7.5 and increasingly active below this value. RTN regulates breathing automaticity about equally during non-REM sleep and quiet waking, conditions under which the respiratory pattern generator is autorhythmic. By contrast, RTN has a much reduced influence on breathing during Viar for surgery skills, science advice, life advice, wanted/unwanted music advice and so much more. Together, they made a dynamic group of personalities that provided a stimulating and encouraging atmosphere that will never be forgotten....

show abstract

Regulation of Breathing and Autonomic Outflows by Chemoreceptors

Cited by 261 publications

References 468 publications

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

The Dynamic Role of Breathing and Cellular Membrane Potentials in the Experience of Consciousness

Neural Control of Respiration by the Retrotrapezoid Nucleus.

Contact Info

Product

Resources

About