Neural-mechanical coupling of breathing in REM sleep

Smith, Curtis A.; Henderson, K. S.; Xi, Lei; Chow, Chin Moi; Eastwood, Peter R.; Dempsey, Jerome A.

doi:10.1152/jappl.1997.83.6.1923

Cited by 21 publications

(12 citation statements)

References 27 publications

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“…As reported before (Fagenholz et al 1976;Sullivan et al 1979;Coote, 1982;Douglas et al 1982a;Douglas et al 1982b;Berthon-Jones & Sullivan, 1984;Smith et al 1997;Horner et al 2002), the HCVR was similar during non-REM sleep and quiet wake but significantly reduced during REM sleep. We also confirm that hypercapnia does not change f R during REM sleep (Berthon-Jones & Sullivan, 1984;Horner et al 2002;Nakamura et al 2007).…”

Section: Loss Of F R Control Contributes To Reduced Chemoreflex Gain supporting

confidence: 76%

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State‐dependent control of breathing by the retrotrapezoid nucleus

Burke

Kanbar

Basting

et al. 2015

The Journal of Physiology

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Key pointsr This study explores the state dependence of the hypercapnic ventilatory reflex (HCVR). We simulated an instantaneous increase or decrease of central chemoreceptor activity by activating or inhibiting the retrotrapezoid nucleus (RTN) by optogenetics in conscious rats.r During quiet wake or non-REM sleep, hypercapnia increased both breathing frequency (f R ) and tidal volume (V T ) whereas, in REM sleep, hypercapnia increased V T exclusively.r Optogenetic inhibition of RTN reduced V T in all sleep-wake states, but reduced fR only during quiet wake and non-REM sleep. RTN stimulation always increased V T but raised f R only in quiet wake and non-REM sleep.r Phasic RTN stimulation produced active expiration and reduced early expiratory airflow (i.e. increased upper airway resistance) only during wake.r We conclude that the HCVR is highly state-dependent. The HCVR is reduced during REM sleep because f R is no longer under chemoreceptor control and thus could explain why central sleep apnoea is less frequent in REM sleep.Abstract Breathing has different characteristics during quiet wake, non-REM or REM sleep, including variable dependence on P CO 2 . We investigated whether the retrotrapezoid nucleus (RTN), a proton-sensitive structure that mediates a large portion of the hypercapnic ventilatory reflex, regulates breathing differently during sleep vs. wake. Electroencephalogram, neck electromyogram, blood pressure, respiratory frequency (f R ) and tidal volume (V T ) were recorded in 28 conscious adult male Sprague-Dawley rats. Optogenetic stimulation of RTN with channelrhodopsin-2, or inhibition with archaerhodopsin, simulated an instantaneous increase or decrease of central chemoreceptor activity. Both opsins were delivered with PRSX8-promoter-containing lentiviral vectors. RTN and catecholaminergic neurons were transduced. During quiet wake or non-REM sleep, hypercapnia (3 or 6% F I,CO 2 ) increased both f R and V T whereas, in REM sleep, hypercapnia increased V T exclusively. RTN inhibition always reduced V T but reduced f R only during quiet wake and non-REM sleep. RTN stimulation always increased V T but raised f R only in quiet wake and non-REM sleep. Blood pressure was unaffected by either stimulation or inhibition. Except in REM sleep, phasic RTN stimulation entrained and shortened the breathing cycle by selectively shortening the post-inspiratory phase. Phasic stimulation also produced active expiration and reduced early expiratory airflow but only during wake. V T is always regulated by RTN and CO 2 but f R is regulated by CO 2 and RTN only when the brainstem pattern generator is in autorhythmic mode (anaesthesia, non-REM sleep, quiet wake). The reduced contribution of RTN to breathing during REM sleep could explain why certain central apnoeas are less frequent during this sleep stage.

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Section: Loss Of F R Control Contributes To Reduced Chemoreflex Gain supporting

confidence: 76%

“… b ; Berthon‐Jones & Sullivan, ; Smith et al . ; Horner et al . ), the HCVR was similar during non‐REM sleep and quiet wake but significantly reduced during REM sleep.…”

Section: Discussionmentioning

confidence: 99%

State‐dependent control of breathing by the retrotrapezoid nucleus

Burke

Kanbar

Basting

et al. 2015

The Journal of Physiology

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“…As reported before (Fagenholz et al, 1976;Sullivan et al, 1979;Coote, 1982;Douglas et al, 1982a;Douglas et al, 1982b;Berthon-Jones & Sullivan, 1984;Smith et al, 1997;Horner et al, 2002), the HCVR was similar during non-REM sleep and quiet wake but significantly reduced during REM sleep. We also confirm that hypercapnia does not change f R during REM sleep (Berthon-Jones & Sullivan, 1984;Horner et al, 2002;Nakamura et al, 2007).…”

Section: Loss Of F R Control Contributes To Reduced Chemoreflex Gain supporting

confidence: 76%

“…However, during REM sleep the hypercapnic ventilatory reflex is reduced to only changes in V T and no longer alters breathing frequency (Fagenholz et al, 1976;Sullivan et al, 1979;Coote, 1982;Douglas et al, 1982a;Douglas et al, 1982b;Berthon-Jones & Sullivan, 1984;Smith et al, 1997;Horner et al, 2002). Furthermore, Orem et al (2005) showed that in hyperventilated conscious cats diaphragmatic EMG recordings re-emerged during REM sleep that were absent during non-REM sleep.…”

Section: State-dependent Control Of Respirationmentioning

confidence: 99%

Neural Control of Respiration by the Retrotrapezoid Nucleus.

Basting¹

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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....

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“…Moreover, the apneic and bradycardic responses to instillation of water or inflation of a balloon in the larynx that did not cause arousals were actually more pronounced during REM sleep than NREM sleep (523). The average diaphragmatic response to airway occlusion was reduced during REM sleep when compared to NREM sleep, but further analysis revealed that this occurred only at times when inhibitory effects of REM sleep on diaphragmatic activity predominated, rather than throughout the state (503). In rabbits, reflex activation of the GG muscle was reduced during both NREM sleep and REM sleep to a larger degree than expected from the concomitant suppression of spontaneous GG muscle activity (185).…”

Section: Neurochemically Distinct Central Neuronal Systems With Statementioning

confidence: 99%

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

Kubin

2016

Comprehensive Physiology

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Upper airway muscles subserve many essential for survival orofacial behaviors, including their important role as accessory respiratory muscles. In the face of certain predisposition of craniofacial anatomy, both tonic and phasic inspiratory activation of upper airway muscles is necessary to protect the upper airway against collapse. This protective action is adequate during wakefulness, but fails during sleep which results in recurrent episodes of hypopneas and apneas, a condition known as the obstructive sleep apnea syndrome (OSA). Although OSA is almost exclusively a human disorder, animal models help unveil the basic principles governing the impact of sleep on breathing and upper airway muscle activity. This article discusses the neuroanatomy, neurochemistry, and neurophysiology of the different neuronal systems whose activity changes with sleep-wake states, such as the noradrenergic, serotonergic, cholinergic, orexinergic, histaminergic, GABAergic and glycinergic, and their impact on central respiratory neurons and upper airway motoneurons. Observations of the interactions between sleep-wake states and upper airway muscles in healthy humans and OSA patients are related to findings from animal models with normal upper airway, and various animal models of OSA, including the chronic-intermittent hypoxia model. Using a framework of upper airway motoneurons being under concurrent influence of central respiratory, reflex and state-dependent inputs, different neurotransmitters, and neuropeptides are considered as either causing a sleep-dependent withdrawal of excitation from motoneurons or mediating an active, sleep-related inhibition of motoneurons. Information about the neurochemistry of state-dependent control of upper airway muscles accumulated to date reveals fundamental principles and may help understand and treat OSA.

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Neural-mechanical coupling of breathing in REM sleep

Cited by 21 publications

References 27 publications

State‐dependent control of breathing by the retrotrapezoid nucleus

State‐dependent control of breathing by the retrotrapezoid nucleus

Neural Control of Respiration by the Retrotrapezoid Nucleus.

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

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