Drug-induced changes in fetal breathing activity and sleep state

1983 ◽  
Vol 61 (4) ◽  
pp. 315-324 ◽  
Author(s):  
Arno H. Jansen ◽  
S. Ioffe ◽  
V. Chernick
Keyword(s):  
Rem Sleep ◽  
Femoral Vein ◽  
Nrem Sleep ◽  
Primary Response ◽  
Sleep State ◽  
Drug Induced ◽  
Fetal Breathing ◽  
Near Term ◽  
Induced Changes ◽  
Stimulation Of

Drugs reported to stimulate fetal breathing (FB) were injected into a femoral vein of near-term fetal iambs during rapid eye movement (REM) and non-REM (NREM) sleep. The primary response to NaCN, 0.25–0.5 mg, a dose which did not flatten the electrocorticogram, was a brief burst of gasping in any sleep state. When injected during REM sleep, NaCN caused the cessation of spontaneous FB and the onset of gasping. Stimulation of FB was observed infrequently. Caffeine (10 mg) and doxapram (3 mg) frequently caused an immediate change in sleep state or arousal. The incidence of FB increased concomitantly with a change to REM sleep or wakefulness (W), but FB still ceased with the onset of NREM sleep. When administered during an episode of spontaneous FB during REM sleep, both caffeine and doxapram caused stimulation of the frequency and depth of breathing. Pilocarpine (4 mg) caused arousal and gasping followed by prolonged vigorous breathing that was dependent on intact carotid sinus nerves, Indomethacin (120 mg over several hours) did not affect sleep states but induced FB in both NREM and REM sleep. In summary, in the fetus the primary effect of NaCN is to suppress spontaneous FB and induce gasping and the effects of pilocarpine, caffeine, and doxapram are intimately related to sleep states or arousal. Indomethacin causes the conversion from episodic fetal to continuous postnatal-type breathing. These data indicate the importance of assessing fetal state of consciousness in interpreting the respiratory response to drugs.

scholarly journals 0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A30-A30
Author(s):  
J Stucynski ◽  
A Schott ◽  
J Baik ◽  
J Hong ◽  
F Weber ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Sleep Regulation ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulation Of

Abstract Introduction The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear. Methods The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics. Results Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep. Conclusion These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry. Support R01 HL149133

Circadian rhythms of sleep and wakefulness in mice: analysis using long-term automated recording of sleep

1985 ◽  
Vol 248 (3) ◽  
pp. R320-R330 ◽  
Author(s):  
G. S. Richardson ◽  
M. C. Moore-Ede ◽  
C. A. Czeisler ◽  
W. C. Dement
Keyword(s):  
Circadian Rhythms ◽  
Rem Sleep ◽  
Wheel Running ◽  
Nrem Sleep ◽  
Sleep State ◽  
Continuous Darkness ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Significant Difference ◽  
Wake State

Circadian rhythms of wheel-running activity and polygraphically defined wakefulness, rapid-eye-movement (REM) sleep and non-REM (NREM) sleep were continuously observed in ten mice (Mus musculus) under both alternating light-dark (LD 12:12) and continuous darkness (DD) conditions. Sleep-wake state was determined automatically using a computer-based method that allowed continuous recordings of from 60 to 280 days in duration. The sleep-wake state percentages (of the circadian cycle) thus obtained were in substantial agreement with other estimates for this or similar strains and showed no significant difference between LD 12:12 (wake 54.3%, NREM sleep 38.1%, REM sleep 7.6%) and DD (wake 53.1%, NREM sleep 39.9%, REM sleep 7.0%) conditions. All 10 mice exhibited clear circadian rhythms in each of the three states and wheel-running activity under both lighting conditions for the entire duration of observation. Probability functions, computed using stationary sections of data from all 10 mice, showed distinct waveforms for all three states and wheel running. These waveforms were remarkably similar under entrained and free-running conditions. This documentation of sustained circadian rhythmicity in sleep-wake state throughout observations of unprecedented length contradicts the currently common assertion that circadian control of sleep state is weaker than that of activity.

Shedding old assumptions and consolidating what we know: Toward an attention-based model of dreaming

2000 ◽  
Vol 23 (6) ◽  
pp. 924-928 ◽  
Author(s):  
Russell Conduit ◽  
Sheila Gillard Crewther ◽  
Grahame Coleman
Keyword(s):  
Rem Sleep ◽  
Cognitive Activity ◽  
Nrem Sleep ◽  
Theoretical Models ◽  
Subsequent Recall ◽  
Mental Events ◽  
Pgo Waves ◽  
Stimulation Of

Most current theoretical models of dreaming are built around an assumption that dream reports collected on awakening provide unbiased sampling of previous cognitive activity during sleep. However, such data are retrospective, requiring the recall of previous mental events from sleep on awakening. Thus, it is possible that dreaming occurs throughout sleep and differences in subsequent dream reports are owing to systematic differences in our ability to recall mentation on awakening. For this reason, it cannot be concluded with certainty that sleep cognition is more predominant or in any way different during REM compared to NREM sleep. It is our contention that REM sleep and ponto-geniculo-occipital (PGO) waves do not necessarily represent “pseudosensory” stimulation of the cortex in the generation of dreams, but might rather represent enhanced arousal of attention mechanisms during sleep, which results in the subsequent recall of attended mentation on awakening.[Hobson et al.; Nielsen; Revonsuo; Solms; Vertes & Eastman]

Covert REM sleep effects on REM mentation: Further methodological considerations and supporting evidence

2000 ◽  
Vol 23 (6) ◽  
pp. 1040-1057 ◽  
Author(s):  
Tore A. Nielsen
Keyword(s):  
Eye Movements ◽  
Future Development ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Explanatory Models ◽  
Supporting Evidence ◽  
Sleep State ◽  
Detailed Understanding ◽  
Methodological Considerations

Whereas many researchers see a heuristic potential in the covert REM sleep model for explaining NREM sleep mentation and associated phenomena, many others are unconvinced of its value. At present, there is much circumstantial support for the model, but validation is lacking on many points. Supportive findings from several additional studies are summarized with results from two new studies showing (1) NREM mentation is correlated with duration of prior REM sleep, and (2) REM sleep signs (eye movements, phasic EMG) occur frequently in NREM sleep. The covert REM sleep model represents one class of explanatory models that combines the two assumptions of mind-body isomorphism and a 1-gen mentation generator; its future development will depend largely upon a more detailed understanding of sleep state interactions and their contribution to mind-body isomorphisms.

Changes in ventilation and chest wall mechanics during sleep in normal adolescents

1981 ◽  
Vol 51 (3) ◽  
pp. 557-564 ◽  
Author(s):  
E. Tabachnik ◽  
N. L. Muller ◽  
A. C. Bryan ◽  
H. Levison
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Muscle Activity ◽  
Minute Ventilation ◽  
Nrem Sleep ◽  
Work Load ◽  
Sleep State ◽  
Rib Cage ◽  
Diaphragmatic Muscle ◽  
Normal Adolescents

The effect of sleep state on ventilation and the mechanics of breathing was studied in nine normal adolescents by use of a respiratory inductive plethysmograph and surface electromyogram electrodes. Minute ventilation was state dependent (P less than 0.01), decreasing by a mean of 8% from wakefulness to nonrapid-eye-movement (NREM) sleep and increasing 4% from NREM to rapid-eye-movement (REM) sleep. These changes were caused by changes in respiratory rate. Tidal volume (VT) was not affected by sleep state (P greater than 0.10). The pattern of breathing during wakefulness was similar to that of REM sleep. During NREM sleep intercostal and diaphragmatic muscle activity increased by a mean of 34% and 11%, respectively, as compared with wakefulness, indicating an increase in the respiratory work load. This was accompanied by a substantial increase in rib cage contribution to VT. REM sleep was associated with a marked decrease in intercostal muscle activity (P less than 0.05) and a diminished rib cage contribution; VT was maintained due to a mean increase of 34% in diaphragmatic muscle activity (P less than 0.05).

Control of organ blood flow in fetal sheep during normoxia and hypoxia

1989 ◽  
Vol 257 (4) ◽  
pp. H1132-H1139 ◽  
Author(s):  
A. H. Jansen ◽  
J. Belik ◽  
S. Ioffe ◽  
V. Chernick
Keyword(s):  
Blood Flow ◽  
Rem Sleep ◽  
Skeletal Muscles ◽  
Nrem Sleep ◽  
Adaptation To Hypoxia ◽  
Organ Blood Flow ◽  
Fetal Sheep ◽  
Blood Flows ◽  
Carotid Bodies ◽  
Fetal Breathing

The role of peripheral chemoreceptors in the circulatory adaptation to hypoxia and the effects of rapid-eye-movement (REM) and non-REM (NREM) sleep and breathing activity on organ blood flow were assessed in fetal sheep. Blood flow was measured with isotope-labeled microspheres on intact, vagotomized (VX), and sinoaortic-denervated (SAD) fetuses. Denervation did not change the biventricular cardiac output (Biv. CO) or organ blood flows during normoxia. In intact fetuses the blood flow was increased during hypoxemia in brain, adrenals, and heart but not in kidneys, skeletal muscles, or placenta. The increase in organ blood flow during hypoxemia was reduced in the VX group and even more in SAD fetuses, but in the latter group, blood flow was still increased in mid-brain, medulla, pons, skeletal muscles, and heart. Sleep states per se did not significantly affect the blood flow to any organs tested. However, the Biv. CO and blood flow to all organs except kidneys and adrenals was increased during fetal breathing in REM sleep. We conclude that 1) during moderate hypoxemia both aortic and carotid bodies plus an additional mechanism are involved in redistributing fetal blood flow, and 2) changes in organ perfusion during REM sleep are due to concomitant fetal breathing.

Stimulation of fetal breathing activity by beta-adrenergic mechanisms

1986 ◽  
Vol 60 (6) ◽  
pp. 1938-1945 ◽  
Author(s):  
A. H. Jansen ◽  
S. Ioffe ◽  
V. Chernick
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Constant Infusion ◽  
Lingual Artery ◽  
Rapid Eye Movement ◽  
Inhibitory Mechanisms ◽  
Fetal Breathing ◽  
Carotid Body Chemoreceptors ◽  
Arterial Po2

Experiments were done on chronically prepared fetal lambs, 125–135 days gestation, to test the effects of various catecholamines on fetal breathing (FB) as well as the influence of isoproterenol on the fetal respiratory response to hypoxemia. Bolus injections of epinephrine, norepinephrine, and isoproterenol (5–20 micrograms) were administered via the lingual artery or femoral or jugular vein during periods of FB activity or apnea. The effects of epinephrine and norepinephrine on FB were variable and not statistically significant. Isoproterenol produced a significant increase in FB, frequency of breathing, and mean inspiratory effort, when infused during rapid-eye-movement (REM) sleep but it failed to induce FB during non-rapid-eye-movement (NREM) sleep. The positive response during REM sleep was absent following pretreatment with 3–5 mg propranolol and after bilateral section of the sinus nerves. The effect of hypoxia on FB was tested before and during constant infusion of isoproterenol (1 microgram/min iv). A reduction of the fetal arterial PO2 by 3–10 Torr produced the characteristic depression of FB in either situation. These results indicate that the fetal carotid body chemoreceptors can reflexly stimulate FB under certain circumstances but that their effectiveness is limited by more powerful inhibitory mechanisms such as those operative during NREM sleep and hypoxemia.

scholarly journals An ether stressor increases REM sleep in rats: possible role of prolactin

2000 ◽  
Vol 279 (5) ◽  
pp. R1590-R1598 ◽  
Author(s):  
B. Bodosi ◽  
F. Obál ◽  
J. Gardi ◽  
J. Komlódi ◽  
J. Fang ◽  
...  
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Wave Activity ◽  
Intracerebroventricular Administration ◽  
Light Onset ◽  
Hypophysectomized Rats ◽  
Sleep Alterations ◽  
Stimulation Of

Sleep alterations after a 1-min exposure to ether vapor were studied in rats to determine if this stressor increases rapid eye-movement (REM) sleep as does an immobilization stressor. Ether exposure before light onset or dark onset was followed by significant increases in REM sleep starting ∼3–4 h later and lasting for several hours. Non-REM (NREM) sleep and electroencephalographic slow-wave activity during NREM sleep were not altered. Exposure to ether vapor elicited prolactin (Prl) secretion. REM sleep was not promoted after ether exposure in hypophysectomized rats. If the hypophysectomy was partial and the rats secreted Prl after ether exposure, then increases in REM sleep were observed. Intracerebroventricular administration of an antiserum to Prl decreased spontaneous REM sleep and inhibited ether exposure-induced REM sleep. The results indicate that a brief exposure to ether vapor is followed by increases in REM sleep if the Prl response associated with stress is unimpaired. This suggests that Prl, which is a previously documented REM sleep-promoting hormone, may contribute to the stimulation of REM sleep after ether exposure.

scholarly journals Restraint increases prolactin and REM sleep in C57BL/6J mice but not in BALB/cJ mice

2001 ◽  
Vol 281 (3) ◽  
pp. R846-R854 ◽  
Author(s):  
Peter Meerlo ◽  
Amy Easton ◽  
Bernard M. Bergmann ◽  
Fred W. Turek
Keyword(s):  
Rem Sleep ◽  
Restraint Stress ◽  
Social Defeat ◽  
Nrem Sleep ◽  
Sleep Stages ◽  
Social Defeat Stress ◽  
Promoting Effect ◽  
Different Strains ◽  
And Function ◽  
Induced Changes

Sleep is generally considered to be a recovery from prior wakefulness. The architecture of sleep not only depends on the duration of wakefulness but also on its quality in terms of specific experiences. In the present experiment, we studied the effects of restraint stress on sleep architecture and sleep electroencephalography (EEG) in different strains of mice (C57BL/6J and BALB/cJ). One objective was to determine if the rapid eye movement (REM) sleep-promoting effects of restraint stress previously reported for rats would also occur in mice. In addition, we examined whether the effects of restraint stress on sleep are different from effects of social defeat stress, which was found to have a non-REM (NREM) sleep-promoting effect. We further measured corticosterone and prolactin levels as possible mediators of restraint stress-induced changes in sleep. Adult male C57BL/6J and BALB/cJ mice were subjected to 1 h of restraint stress in the middle of the light phase. To control for possible effects of sleep loss per se, the animals were also kept awake for 1 h by gentle handling. Restraint stress resulted in a mild increase in NREM sleep compared with baseline, but, overall, this effect was not significantly different from sleep deprivation by gentle handling. In contrast, restraint stress caused a significant increase in REM sleep compared with handling in the C57BL/6J mice but not in BALB/cJ mice. Corticosterone levels were significantly and similarly elevated after restraint in both strains, but prolactin was increased only in the C57BL/6J mice. In conclusion, this study shows that the restraint stress-induced increase in REM sleep in mice is strongly strain dependent. The concomitant increases in prolactin and REM sleep in the C57BL/6J mice, but not in BALB/cJ mice, suggest prolactin may be involved in the mechanism underlying restraint stress-induced REM sleep. Furthermore, this study confirms that different stressors differentially affect NREM and REM sleep. Whereas restraint stress promotes REM sleep in C57BL/6J mice, we previously found that in the same strain, social defeat stress promotes NREM sleep. As such, studying the consequences of specific stressful stimuli may be an important tool to unravel both the mechanism and function of different sleep stages.

scholarly journals P142 Head flexion has the greatest impact on OSA severity during REM sleep

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A67-A68
Author(s):  
A Tate ◽  
V Kurup ◽  
B Shenoy ◽  
C Freakley ◽  
P Eastwood ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Interaction Effect ◽  
Head Rotation ◽  
Nrem Sleep ◽  
Outcome Variable ◽  
Sleep State ◽  
Respiratory Event ◽  
Supine Sleep ◽  
Logistic Mixed Effects Model ◽  
Head Flexion

Abstract Introduction Recent work has shown that head flexion has a modest worsening effect and head rotation has a modest protective effect on OSA severity. However, there is substantial variability both within and between individuals. In this analysis we aimed to identify if this variability is explained by sleep-state, BMI, age or sex. Methods 28 participants provided informed consent and were studied using diagnostic polysomnography with the addition of a customised, accelerometry based, head posture measurement device. For each epoch during supine sleep, the sleep state (NREM/REM), average head flexion (degrees) and average head rotation (degrees) were recorded. A logistic mixed effects model was fit across all epochs with the anthropometrics (BMI, sex, age), sleep state, average head flexion and average head rotation as explanatory variables with the absence/presence of one or more respiratory event(s) as the binary outcome variable. Results In total, 2122 of 5369 supine sleep epochs had a respiratory event. Three participants had no supine sleep. There were significant interaction effects for flexion-rotation, BMI-rotation and REM-flexion. The REM-flexion interaction effect was the strongest interaction effect with an odds ratio per 5 degrees of head flexion in REM sleep of 1.47 (95% CI: 1.13 – 1.86). Discussion Head flexion related worsening of OSA severity is greatest during REM sleep. This may be explained by attenuated upper airway neuromuscular activation in REM sleep compared with NREM sleep.

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