REM-sleep timing is controlled homeostatically by accumulation of REM-sleep propensity in non-REM sleep

1994 ◽  
Vol 266 (6) ◽  
pp. R1992-R2000 ◽  
Author(s):  
J. H. Benington ◽  
H. C. Heller
Keyword(s):  
Rem Sleep ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Sleep Episode ◽  
Sleep Timing ◽  
Sleep Maintenance ◽  
Oscillatory Mechanism ◽  
Episode Duration ◽  
Full Day ◽  
Sleep Propensity

Sleep structure in the rat was characterized during uninterrupted full-day recordings using an analytic procedure that identifies rapid eye movement (REM) sleep episodes based on REM-sleep-onset electroencephalograph phenomena, hence independently of REM-sleep duration. The data were used to determine whether REM-sleep timing is controlled homeostatically or by an oscillatory mechanism. The findings and conclusions are that 1) non-REM (NREM) sleep episode duration is positively correlated with prior REM-sleep episode duration, suggesting that REM-sleep expression is permissive of NREM sleep; 2) mean NREM-sleep episode duration decreases after repeated brief REM-sleep episodes (< 30 s), also suggesting that discharge of REM-sleep propensity is essential for NREM-sleep expression; 3) REM-sleep episode duration is independent of prior sleep history, suggesting that REM-sleep maintenance is controlled by factors other than accumulated REM-sleep propensity; 4) brief REM-sleep episodes occur progressively more frequently over the course of the NREM-sleep interval between sustained REM-sleep episodes (> 30 s), suggesting that REM-sleep propensity increases progressively within episodes of NREM sleep; and 5) the diurnal cycle of REM-sleep expression primarily reflects modulation in the efficiency of REM-sleep maintenance. These findings support the hypothesis that REM-sleep timing is controlled by accumulation of REM-sleep propensity during NREM sleep.

scholarly journals Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

2014 ◽  
Vol 112 (2) ◽  
pp. 584-589 ◽  
Author(s):  
Christa J. Van Dort ◽  
Daniel P. Zachs ◽  
Jonathan D. Kenny ◽  
Shu Zheng ◽  
Rebecca R. Goldblum ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Cholinergic Neurons ◽  
Nrem Sleep ◽  
Sleep Regulation ◽  
Natural Sleep ◽  
Sleep Episode ◽  
Episode Duration ◽  
Laterodorsal Tegmentum ◽  
Mesopontine Tegmentum

Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.

scholarly journals A study on sleep apnea in patients with abnormal sewda type of depression

2020 ◽  
pp. 1-8
Author(s):  
Aman Gul ◽  
Nassirhadjy Memtily ◽  
Pirdun Mijit ◽  
Palidan Wushuer ◽  
Ainiwaer Talifu ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Sleep Onset ◽  
Sleep Time ◽  
Sleep Efficiency ◽  
Control Group ◽  
Poor Sleep ◽  
Sleep Structure ◽  
Maintenance Rate ◽  
Sleep Maintenance ◽  
Insomnia Symptoms

Objective: To preliminarily investigate the clinical features and PSG in abnormal sewda-type depressive insomnia. Methods: A total of 127 abnormal sewda-type depressive insomnia patients were evaluated with overnight PSG, and 32 normal participants were compared. Results: Patients with abnormal sewda-type depressive insomnia were compared with the control group; the sleep symptoms showed a long incubation period of sleep, low sleep maintenance rate, low sleep efficiency and poor sleep quality as well as daytime dysfunction. At process and continuity of sleep: Total sleep time, sleep efficiency, sleep maintenance rate in abnormal sewda-type depressive insomnia group were shorter than the control group. Wake after sleep onset, and sleep latency were longer than the control group. At sleep structure: N1 ratio and N2 ratio in depressive insomnia group were longer than the control group, N3 ratio and REM sleep ratio shorter than the control group. At REM index: REM latency, REM cycles, and REM sleep time were shorter than the control group. Conclusion: Insomnia symptoms in abnormal sewda-type depression comorbid insomnia patients were similar to the ordinary insomnia patients. The PSG characteristics had significant changes in sleep process, sleep structure and REM indicators. The severity of the abnormal sewda-type depression was closely related to REM indicators. Change of REM sleep characteristics may be the specificity, and these could be taken as reference in diagnosis and identification of abnormal sewda-type depressive insomnia.

scholarly journals Dream Generation and Recall in Daytime NREM Sleep of Patients With Narcolepsy Type 1

2020 ◽  
Vol 14 ◽  
Author(s):  
Carlo Cipolli ◽  
Fabio Pizza ◽  
Claudia Bellucci ◽  
Michela Mazzetti ◽  
Giovanni Tuozzi ◽  
...  
Keyword(s):  
Cognitive Processes ◽  
Rem Sleep ◽  
Healthy Subjects ◽  
Structural Organization ◽  
Sleep Onset ◽  
Negative Attitude ◽  
Nrem Sleep ◽  
The Difference ◽  
Multiple Sleep Latency

The less rigid architecture of sleep in patients with narcolepsy type 1 (NT1) compared with healthy subjects may provide new insights into some unresolved issues of dream experience (DE), under the assumption that their DE frequencies are comparable. The multiple transition from wakefulness to REM sleep (sleep onset REM period: SOREMP) during the five trials of the Multiple Sleep Latency Test (MSLT) appears of particular interest. In MSLT studies, NT1 patients reported a DE after about 80% of SOREMP naps (as often as after nighttime REM sleep of themselves and healthy subjects), but only after about 30% of NREM naps compared to 60% of daytime and nighttime NREM sleep of healthy subjects. To estimate accurately the “real” DE frequency, we asked participants to report DE (“dream”) after each MSLT nap and, in case of failure, to specify if they were unable to retrieve any content (“white dream”) or DE did not occur (“no-dream”). The proportions of dreams, white dreams, and no dreams and the indicators of structural organization of DEs reported after NREM naps by 17 adult NT1 patients were compared with those reported by 25 subjects with subjective complaints of excessive daytime sleepiness (sc-EDS), who take multiple daytime NREM naps. Findings were consistent with the hypothesis of a failure in recall after awakening rather than in generation during sleep: white dreams were more frequent in NT1 patients than in sc-EDS subjects (42.86 vs 17.64%), while their frequency of dreams plus white dreams were similar (67.86 and 61.78%) and comparable with that of NREM-DEs in healthy subjects. The longer and more complex NREM-DEs of NT1 patients compared with sc-EDS subjects suggest that the difficulty in DE reporting depends on their negative attitude toward recall of contents less vivid and bizarre than those they usually retrieve after daytime SOREMP and nighttime REM sleep. As this attitude may be reversed by some recall training before MSLT, collecting wider amounts of DE reports after NREM naps would cast light on both the across-stage continuity in the functioning of cognitive processes underlying DE and the difference in content and structural organization of SOREM-DEs preceded by N1 or also N2 sleep.

scholarly journals Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats

2008 ◽  
Vol 295 (6) ◽  
pp. R2041-R2049 ◽  
Author(s):  
Joshi John ◽  
Lalini Ramanathan ◽  
Jerome M. Siegel
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Glutamate Release ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Progressive Increase ◽  
High Temporal Resolution ◽  
Hypothalamic Region ◽  
Rapid Changes ◽  
Freely Behaving

The histamine-containing posterior hypothalamic region (PH-TMN) plays a key role in sleep-wake regulation. We investigated rapid changes in glutamate release in the PH-TMN across the sleep-wake cycle with a glutamate biosensor that allows the measurement of glutamate levels at 1- to 4-s resolution. In the PH-TMN, glutamate levels increased in active waking (AW) and rapid eye movement (REM) sleep compared with quiet waking and nonrapid eye movement (NREM) sleep. There was a rapid (0.6 ± 1.8 s) and progressive increase in glutamate levels at REM sleep onset. A reduction in glutamate levels consistently preceded the offset of REM sleep by 8 ± 3 s. Short-duration sleep deprivation resulted in a progressive increase in glutamate levels in the PH-TMN, perifornical-lateral hypothalamus (PF-LH), and cortex. We found that in the PF-LH, glutamate levels took a longer time to return to basal values compared with the time it took for glutamate levels to increase to peak values during AW onset. This is in contrast to other regions we studied in which the return to baseline values after AW was quicker than their rise with waking onset. In summary, we demonstrated an increase in glutamate levels in the PH-TMN with REM/AW onset and a drop in glutamate levels before the offset of REM. High temporal resolution measurement of glutamate levels reveals dynamic changes in release linked to the initiation and termination of REM sleep.

scholarly journals Vesicular GABA-transporter neurons in the zona incerta are maximally active during non rapid-eye movement (NREM) and rapid-eye movement (REM) sleep

2020 ◽  
Author(s):  
Carlos Blanco-Centurion ◽  
SiWei Luo ◽  
Aurelio Vidal-Ortiz ◽  
Priyattam J. Shiromani
Keyword(s):  
Eye Movement ◽  
Lateral Hypothalamus ◽  
Rem Sleep ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Zona Incerta ◽  
Imaging Method ◽  
Rapid Eye Movement ◽  
Gaba Transporter

AbstractSleep and wake are opposing behavioral states controlled by the activity of specific neurons. The neurons responsible for sleep/wake control have not been fully identifed due to the lack of in-vivo high throughput technology. We use the deep-brain calcium (Ca2+) imaging method to identify activity of hypothalamic neurons expressing the vesicular GABA transporter (vGAT), a marker of GABAergic neurons. vGAT-cre mice (n=5) were microinjected with rAAV-FLEX-GCaMP6M into the lateral hypothalamus and 21d later the Ca2+ influx in vGAT neurons (n=372) was recorded in freely-behaving mice during waking (W), NREM and REM sleep. Post-mortem analysis revealed the lens tip located in the zona incerta/lateral hypothalamus (ZI-LH) and the change in fluorescence of neurons in the field of view was as follows: 54.9% of the vGAT neurons had peak fluorescence during REM sleep (REM-max), 17.2% were NREM-max, 22.8% were wake-max while 5.1% were both wake+REM max. Thus, three quarters of the recorded vGAT neurons in the ZI-LH were most active during sleep. In the NREM-max group Ca2+ fluorescence anticipated the initiation of NREM sleep onset and remained high throughout sleep (NREM and REM sleep). In the REM-max neurons Ca2+fluorescence increased before the onset of REM sleep and stayed elevated during the episode. Activation of the vGAT NREM-max neurons in the zona incerta and dorsal lateral hypothalamus would inhibit the arousal neurons to initiate and maintain sleep.

scholarly journals 317 Sleep-wake survival dynamics in people with insomnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A127-A127
Author(s):  
Lieke Hermans ◽  
Marta Regis ◽  
Pedro Fonseca ◽  
Bertram Hoondert ◽  
Tim Leufkens ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Sleep Quality ◽  
Rem Sleep ◽  
Scale Parameter ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Sleep Fragmentation ◽  
Healthy Controls ◽  
Shape Parameters ◽  
Impaired Sleep

Abstract Introduction Assessing objective measures of sleep fragmentation could yield important features reflecting impaired sleep quality in people with insomnia. Survival analysis allows the specific examination of the stability of NREM sleep, REM sleep and wake. The objective of this study was to assess the differences between survival dynamics of NREM sleep, REM sleep and wake between people with insomnia and healthy controls. Methods We analyzed polysomnography recordings from 88 people with insomnia and 92 healthy controls. For each participant, survival dynamics of REM sleep, NREM sleep and wake were represented using Weibull distributions. We used lasso penalized linear regression to analyze the difference between participant groups with respect to the Weibull scale and shape parameters, while correcting for age, sex, total sleep time and relevant interaction effects. Because comparisons were done for scale and shape parameters of REM sleep, NREM sleep and wake, a Bonferroni correction was applied, resulting in an alpha value of 0.05/6 = 0.0083. Results Significant effects of group were found for the NREM scale parameter (unstandardized model coefficient B=-0.79, t=-3.0, p=0.0035), and for the scale and shape parameters of wake (scale parameter B=7.6, t=2.8, p=0.0065; shape parameter B=0.20, t=2.9, p=0.0048). Results indicated that people with insomnia had less stable NREM sleep and more stable wake after sleep onset compared to healthy controls. Additionally, the altered distribution of wake segment lengths indicated an increased difficulty to fall asleep after longer awakenings in the insomnia group. However, these differences were mainly observed in younger participants. Significant effects of group for the survival parameters of REM sleep were not found. Conclusion As illustrated by our results, survival analysis can be very useful for disentangling different types of sleep fragmentation in people with insomnia. For instance, the current findings suggest that people with insomnia have an increased fragmentation of NREM sleep, but not necessarily of REM sleep. Additional research into the underlying mechanisms of NREM sleep fragmentation could possibly lead to a better understanding of impaired sleep quality in people with insomnia, and consequently to improved treatment. Support (if any):

I. Time course of interventions and recovery sleep

2002 ◽  
Vol 283 (2) ◽  
pp. R521-R526 ◽  
Author(s):  
Esther Werth ◽  
Kimberly A. Cote ◽  
Eva Gallmann ◽  
Alexander A. Borbély ◽  
Peter Achermann
Keyword(s):  
Sleep Deprivation ◽  
Rem Sleep ◽  
Time Course ◽  
Early Morning ◽  
Adult Males ◽  
Sleep Regulation ◽  
Rem Sleep Deprivation ◽  
Sleep Episode ◽  
Recovery Sleep ◽  
Sleep Propensity

Although repeated selective rapid eye movement (REM) sleep deprivation by awakenings during nighttime has shown that the number of sleep interruptions required to prevent REM sleep increases within and across consecutive nights, the underlying regulatory processes remained unspecified. To assess the role of circadian and homeostatic factors in REM sleep regulation, REM sleep was selectively deprived in healthy young adult males during a daytime sleep episode (7–15 h) after a night without sleep. Circadian REM sleep propensity is known to be high in the early morning. The number of interventions required to prevent REM sleep increased from the first to the third 2-h interval by a factor of two and then leveled off. Only a minor REM sleep rebound (11.6%) occurred in the following undisturbed recovery night. It is concluded that the limited rise of interventions during selective daytime REM sleep deprivation may be due to the declining circadian REM sleep propensity, which may partly offset the homeostatic drive and the sleep-dependent disinhibition of REM sleep.

scholarly journals Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kun-Ming Ni ◽  
Xiao-Jun Hou ◽  
Ci-Hang Yang ◽  
Ping Dong ◽  
Yue Li ◽  
...  
Keyword(s):  
Eye Movement ◽  
Nicotinic Acetylcholine Receptors ◽  
Rem Sleep ◽  
Sleep Onset ◽  
Cholinergic Neurons ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Rapid Eye Movement

Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement (REM) sleep and arousal. Using transgenic mice in which channelrhdopsin-2 is selectively expressed in cholinergic neurons, we show that optical stimulation of cholinergic inputs to the thalamic reticular nucleus (TRN) activates local GABAergic neurons to promote sleep and protect non-rapid eye movement (NREM) sleep. It does not affect REM sleep. Instead, direct activation of cholinergic input to the TRN shortens the time to sleep onset and generates spindle oscillations that correlate with NREM sleep. It does so by evoking excitatory postsynaptic currents via α7-containing nicotinic acetylcholine receptors and inducing bursts of action potentials in local GABAergic neurons. These findings stand in sharp contrast to previous reports of cholinergic activity driving arousal. Our results provide new insight into the mechanisms controlling sleep.

scholarly journals 0418 Effect of Acute Administration of DORA-12 on Sleep Impairment in the Aged PS19 Mouse Model of Tauopathy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A160-A160
Author(s):  
K Kam ◽  
M Vetter ◽  
N Berryman ◽  
A Varga
Keyword(s):  
Mouse Model ◽  
Rem Sleep ◽  
Behavior Disorder ◽  
Nrem Sleep ◽  
Acute Effect ◽  
T Test ◽  
Acute Administration ◽  
Rem Behavior Disorder ◽  
Sleep Episode ◽  
Paired T Test

Abstract Introduction Aged PS19 mice (MAPT P301S), a mouse model of tauopathy and neurodegeneration, display reduced NREM and REM sleep starting around 8-9 months before death around 12 months. Here, we tested the acute effect of a dual orexin receptor antagonist (DORA-12) on sleep in 11 mice (5 male, 6 female) at 10.3±1.8 months. Methods Two consecutive 24-hour recordings (12/12hr L:D cycle) were scored semi-automatically for non-REM sleep, REM sleep, and wake in mice implanted with EEG/EMG. Mice were treated with either vehicle (day 1) or 100mg/kg of DORA-12 (day 2) by oral gavage at both ZT0 and ZT9. Results After the first dose at ZT0, both latency to the first NREM sleep episode (paired t-test p=0.002) and to the first REM sleep episode (paired t-test p=0.005) was significantly shorter with DORA-12 (NREM: 20.8±17.8 min.; REM: 23.5±21.2 min.) compared to vehicle (NREM: 49.2±22.3 min.; REM: 127.0±93.3 min.). There was no difference in NREM or REM sleep latency observed after the second dose at ZT9. DORA-12 treatment increased NREM duration across the 24hr period (DORA-12: 664±52 min.; Veh: 601±54 min., paired t-test p=0.007) and also after the 2nd dose (DORA-12: 311±65 min.; Veh: 263±84 min., paired t-test p=0.009). DORA-12 treatment also increased REM duration across 24hrs (DORA-12: 61±30 min.; Veh: 48±29 min., paired t-test p=0.014) but not after the 2nd dose alone (DORA-12: 22±14 min.; Veh: 20±15 min., paired t-test p=0.388). Notably in both vehicle and DORA-12 conditions, we observed apparent dream enactment behavior including mastication, paw grasp, and fore limb extension during REM in 3 of 11 PS19 mice (all male), not typically observed in younger PS19 or age-matched non-transgenic mice, suggestive of a possible REM behavior disorder (RBD) phenotype. Wake-like behaviors occurred during theta-dominant EEG but with an EMG amplitude &gt;4SD the preceding NREM sleep baseline for at least &gt; 1sec. Conclusion In aged PS19 mice, DORA-12 was found to decrease the latency to NREM and REM after the first dose while also increasing NREM and REM duration across the entire 24hr recording period. We also capture a heretofore undescribed RBD-like phenotype in aged PS19 tauopathy mice. Support Merck MISP

scholarly journals REM sleep-dependent short-term and long-term hourglass processes in the ultradian organization and recovery of REM sleep in the rat

SLEEP ◽  
2020 ◽  
Vol 43 (8) ◽  
Author(s):  
Adrián Ocampo-Garcés ◽  
Alejandro Bassi ◽  
Enzo Brunetti ◽  
Jorge Estrada ◽  
Ennio A Vivaldi
Keyword(s):  
Sleep Deprivation ◽  
Rem Sleep ◽  
Transition Probability ◽  
Nrem Sleep ◽  
Short Term ◽  
Rem Sleep Deprivation ◽  
Sleep Episode ◽  
Organization Of Sleep ◽  
Sleep Transition

Abstract Study Objectives To evaluate the contribution of long-term and short-term REM sleep homeostatic processes to REM sleep recovery and the ultradian organization of the sleep wake cycle. Methods Fifteen rats were sleep recorded under a 12:12 LD cycle. Animals were subjected during the rest phase to two protocols (2T2I or 2R2I) performed separately in non-consecutive experimental days. 2T2I consisted of 2 h of total sleep deprivation (TSD) followed immediately by 2 h of intermittent REM sleep deprivation (IRD). 2R2I consisted of 2 h of selective REM sleep deprivation (RSD) followed by 2 h of IRD. IRD was composed of four cycles of 20-min RSD intervals alternating with 10 min of sleep permission windows. Results REM sleep debt that accumulated during deprivation (9.0 and 10.8 min for RSD and TSD, respectively) was fully compensated regardless of cumulated NREM sleep or wakefulness during deprivation. Protocol 2T2I exhibited a delayed REM sleep rebound with respect to 2R2I due to a reduction of REM sleep transitions related to enhanced NREM sleep delta-EEG activity, without affecting REM sleep consolidation. Within IRD permission windows there was a transient and duration-dependent diminution of REM sleep transitions. Conclusions REM sleep recovery in the rat seems to depend on a long-term hourglass process activated by REM sleep absence. Both REM sleep transition probability and REM sleep episode consolidation depend on the long-term REM sleep hourglass. REM sleep activates a short-term REM sleep refractory period that modulates the ultradian organization of sleep states.

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