scholarly journals REM sleep: unique associations with behavior, corticosterone regulation and apoptotic pathways in chronic stress in mice

2018 ◽  
Author(s):  
Mathieu Nollet ◽  
Harriet Hicks ◽  
Andrew P. McCarthy ◽  
Huihai Wu ◽  
Carla S. Möller-Levet ◽  
...  
Keyword(s):  
Machine Learning ◽  
Eye Movement ◽  
Chronic Stress ◽  
Rem Sleep ◽  
Chronic Mild Stress ◽  
Specific Aspect ◽  
Mild Stress ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Apoptotic Pathways

AbstractOne of sleep’s putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience, however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine and behavioral variables and the brain and blood transcriptome in mice exposed to nine weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypical variables revealed that rapid-eye-movement sleep (REMS), corticosterone regulation and coat state were most responsive to UCMS. REMS theta oscillations were enhanced whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus and blood were associated with inflammatory and immune responses. A machine learning approach controlling for unspecific UCMS effects identified transcriptomic predictors for specific phenotypes and their overlap. Transcriptomic predictor sets for the inter-individual variation in REMS continuity and theta activity shared many pathways with corticosterone regulation and in particular pathways implicated in apoptosis, including mitochondrial pathways. Predictor sets for REMS and anhedonia, one of the behavioral changes following UCMS, shared pathways involved in oxidative stress, cell proliferation and apoptosis. RNA predictor sets for non-NREMS parameters showed no overlap with other phenotypes. These novel data identify REMS as a core and early element of the response to chronic stress, and identify apoptotic pathways as a putative mechanism by which REMS mediates adaptation to stressful waking experiences.Significance StatementSleep is responsive to experiences during wakefulness and is altered in stress-related disorders. Whether sleep changes primarily concern rapid-eye-movement sleep (REMS) or non-REM sleep, and how they correlate with stress hormones, behavioral and transcriptomic responses remained unknown. We demonstrate using unpredictable chronic (9-weeks) mild stress that REMS is the most responsive of all the measured sleep characteristics, and correlates with deficiency in corticosterone regulation. An unbiased machine learning, controlling for unspecific effects of stress, revealed that REMS correlated with RNA predictor sets enriched in apoptosis including mitochondrial pathways. Several pathways were shared with predictors of corticosterone and behavioral responses. This unbiased approach point to apoptosis as a molecular mechanism by which REMS mediates adaptation to an ecologically relevant waking experience.

scholarly journals REM sleep’s unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice

2019 ◽  
Vol 116 (7) ◽  
pp. 2733-2742 ◽  
Author(s):  
Mathieu Nollet ◽  
Harriet Hicks ◽  
Andrew P. McCarthy ◽  
Huihai Wu ◽  
Carla S. Möller-Levet ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Specific Aspect ◽  
Mild Stress ◽  
Behavioral Disturbances ◽  
Survival Pathways ◽  
Proliferation And Apoptosis ◽  
Machine Learning Approach ◽  
Apoptotic Pathways ◽  
And Behavior

One of sleep’s putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience; however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine, and behavioral variables, as well as the brain and blood transcriptome in mice exposed to 9 weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypic variables revealed that rapid–eye-movement sleep (REMS), corticosterone regulation, and coat state were most responsive to UCMS. REMS theta oscillations were enhanced, whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus, and blood were associated with inflammatory and immune responses. A machine-learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters that were enriched in 193 pathways, including some involved in stem cells, immune response, and apoptosis and survival. Only three pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS and anhedonia shared pathways involved in oxidative stress, cell proliferation, and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences.

High-throughput visual assessment of sleep stages in mice using machine learning

SLEEP ◽  
2021 ◽  
Author(s):  
Brian Geuther ◽  
Mandy Chen ◽  
Raymond J Galante ◽  
Owen Han ◽  
Jie Lian ◽  
...  
Keyword(s):  
Machine Learning ◽  
Eye Movement ◽  
High Throughput ◽  
Data Augmentation ◽  
Sleep Stage ◽  
Visual Assessment ◽  
Video Data ◽  
Sleep Stages ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep

Abstract Study Objectives Sleep is an important biological process that is perturbed in numerous diseases, and assessment its substages currently requires implantation of electrodes to carry out electroencephalogram/electromyogram (EEG/EMG) analysis. Although accurate, this method comes at a high cost of invasive surgery and experts trained to score EEG/EMG data. Here, we leverage modern computer vision methods to directly classify sleep substages from video data. This bypasses the need for surgery and expert scoring, provides a path to high-throughput studies of sleep in mice. Methods We collected synchronized high-resolution video and EEG/EMG data in 16 male C57BL/6J mice. We extracted features from the video that are time and frequency-based and used the human expert-scored EEG/EMG data to train a visual classifier. We investigated several classifiers and data augmentation methods. Results Our visual sleep classifier proved to be highly accurate in classifying wake, non-rapid eye movement sleep (NREM), and rapid eye movement sleep (REM) states, and achieves an overall accuracy of 0.92 +/- 0.05 (mean +/- SD). We discover and genetically validate video features that correlate with breathing rates, and show low and high variability in NREM and REM sleep, respectively. Finally, we apply our methods to non-invasively detect that sleep stage disturbances induced by amphetamine administration. Conclusions We conclude that machine learning based visual classification of sleep is a viable alternative to EEG/EMG based scoring. Our results will enable non-invasive high-throughput sleep studies and will greatly reduce the barrier to screening mutant mice for abnormalities in sleep.

GABAergic Regulation of REM Sleep in Reticularis Pontis Oralis and Caudalis in Rats

2003 ◽  
Vol 90 (2) ◽  
pp. 938-945 ◽  
Author(s):  
Larry D. Sanford ◽  
Xiangdong Tang ◽  
Jihua Xiao ◽  
Richard J. Ross ◽  
Adrian R. Morrison
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Escape Behavior ◽  
Aminobutyric Acid ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sprague Dawley ◽  
Site Specific ◽  
Guide Cannulae ◽  
Nucleus Reticularis

The nucleus reticularis pontis oralis (RPO) and nucleus reticularis pontis caudalis (RPC) are implicated in the generation of rapid eye movement sleep (REM). Work in cats has indicated that GABA in RPO plays a role in the regulation of REM. We assessed REM after local microinjections into RPO and RPC of the γ-aminobutyric acid-A (GABAA) agonist, muscimol (MUS), and the GABAA antagonist, bicuculline (BIC). Rats (90-day-old male Sprague-Dawley) were implanted with electrodes for recording electroencephalographs (EEG) and electromyographs (EMG). Guide cannulae were aimed into RPO ( n = 9) and RPC ( n = 8) for microinjecting MUS (200, 1,000.0 μM) and BIC (0.056, 0.333, 1.0, 1,000.0, and 10,000.0 μM). Animals received bilateral microinjections of saline, MUS, and BIC (0.2 μl microinjected at 0.1 μl/min) into each region followed by 6-h sleep recordings. In RPO, MUS (1,000.0 μM) suppressed REM and BIC (1,000.0 μM) enhanced REM. In RPC, MUS (200, 1,000.0 μM) suppressed REM, but BIC (1,000.0 μM and less) did not significantly affect REM. Higher concentrations of BIC (10,000.0 μM) injected into RPO ( n = 9) and RPC ( n = 4) produced wakefulness and escape behavior. The results indicate that GABA in RPO/RPC is involved in the regulation of REM and suggest site-specific differences in this regulation.

scholarly journals Predicting stress resilience and vulnerability: brain-derived neurotrophic factor and rapid eye movement sleep as potential biomarkers of individual stress responses

SLEEP ◽  
2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Brook L W Sweeten ◽  
Amy M Sutton ◽  
Laurie L Wellman ◽  
Larry D Sanford
Keyword(s):  
Eye Movement ◽  
Stress Responses ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Mild Stress ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Stress Resilience ◽  
Potential Biomarker ◽  
Sleep Recording

Abstract Study Objectives To examine the rapid eye movement sleep (REM) response to mild stress as a predictor of the REM response to intense stress and brain-derived neurotrophic factor (BDNF) as a potential biomarker of stress resilience and vulnerability. Methods Outbred Wistar rats were surgically implanted with electrodes for recording electroencephalography (EEG) and electromyogram (EMG) and intraperitoneal Data loggers to record body temperature. Blood was also obtained to measure circulating BDNF. After recovery, rats were exposed to mild stress (novel chamber, NC) and later intense stress (shock training, ST), followed by sleep recording. Subsequently, rats were separated into resilient (Res; n=27) or vulnerable (Vul; n = 15) based on whether or not there was a 50% or greater decrease in REM after ST compared to baseline. We then compared sleep, freezing, and the stress response (stress-induced hyperthermia, SIH) across groups to determine the effects of mild and intense stress to determine if BDNF was predictive of the REM response. Results REM totals in the first 4 hours of sleep after exposure to NC predicted REM responses following ST with resilient animals having higher REM and vulnerable animals having lower REM. Resilient rats had significantly higher baseline peripheral BDNF compared to vulnerable rats. Conclusions These results show that outbred rats display significant differences in post-stress sleep and peripheral BDNF identifying these factors as potential markers of resilience and vulnerability prior to traumatic stress.

Ventilation during early and late rapid-eye-movement sleep in normal humans

1991 ◽  
Vol 71 (4) ◽  
pp. 1201-1215 ◽  
Author(s):  
J. B. Neilly ◽  
E. A. Gaipa ◽  
G. Maislin ◽  
A. I. Pack
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Minute Ventilation ◽  
Inspiratory Flow ◽  
Respiratory Frequency ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Rib Cage ◽  
Ventilatory Parameters ◽  
Normal Humans

Because successive rapid-eye-movement (REM) sleep periods in the night are longer in duration and have more phasic events, ventilation during late REM sleep might be more affected than in earlier episodes. Despite the increase in eye movement density (EMD) in late REM sleep, average minute ventilation was, however, not reduced compared with that in early REM sleep. Decreases in rib cage motion (mean inspiratory flow of the rib cage) in association with increasing EMD were offset by increments in respiratory frequency. Apart from expiratory time, there were no significant changes in the slopes of the relationships between EMD and specific ventilatory components, from early to late REM sleep periods. However, there was an increase in the number of episodes when ventilation was reduced during late REM sleep. Changes in ventilatory pattern during late REM sleep are due to changes in the underlying nature of REM sleep. The ventilatory response during eye movements is, however, subject specific. Some subjects exhibit large decrements in mean inspiratory flow of the rib cage and increments in respiratory frequency during bursts of eye movement, whereas other individuals demonstrate only small changes in these ventilatory parameters.

scholarly journals MATHEMATICAL PHASE MODEL OF NEURAL POPULATIONS INTERACTION IN MODULATION OF REM/NREM SLEEP

2016 ◽  
Vol 21 (6) ◽  
pp. 794-810 ◽  
Author(s):  
Paolo Acquistapace ◽  
Anna P. Candeloro ◽  
Vladimir Georgiev ◽  
Maria L. Manca
Keyword(s):  
Experimental Data ◽  
Eye Movement ◽  
Rem Sleep ◽  
Reaction Diffusion ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Neuronal Populations ◽  
Neural Populations ◽  
Cyclic Oscillation

Aim of the present study is to compare the synchronization of the classical Kuramoto system and the reaction - diffusion space time Landau - Ginzburg model, in order to describe the alternation of REM (rapid eye movement) and NREM (non-rapid eye movement) sleep across the night. These types of sleep are considered as produced by the cyclic oscillation of two neuronal populations that, alternatively, promote and inhibit the REM sleep. Even if experimental data will be necessary, a possible interpretation of the results has been proposed.

scholarly journals Rapid Eye Movement Sleep Debt Accrues in Mice Exposed to Volatile Anesthetics

2011 ◽  
Vol 115 (4) ◽  
pp. 702-712 ◽  
Author(s):  
Jeremy Pick ◽  
Yihan Chen ◽  
Jason T. Moore ◽  
Yi Sun ◽  
Abraham J. Wyner ◽  
...  
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Volatile Anesthetics ◽  
Dark Phase ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Oxygen Control ◽  
Dark Cycle ◽  
Sleep Debt ◽  
Anesthetic Exposure

Background General anesthesia has been likened to a state in which anesthetized subjects are locked out of access to both rapid eye movement (REM) sleep and wakefulness. Were this true for all anesthetics, a significant REM rebound after anesthetic exposure might be expected. However, for the intravenous anesthetic propofol, studies demonstrate that no sleep debt accrues. Moreover, preexisting sleep debts dissipate during propofol anesthesia. To determine whether these effects are specific to propofol or are typical of volatile anesthetics, the authors tested the hypothesis that REM sleep debt would accrue in rodents anesthetized with volatile anesthetics. Methods Electroencephalographic and electromyographic electrodes were implanted in 10 mice. After 9-11 days of recovery and habituation to a 12 h:12 h light-dark cycle, baseline states of wakefulness, nonrapid eye movement sleep, and REM sleep were recorded in mice exposed to 6 h of an oxygen control and on separate days to 6 h of isoflurane, sevoflurane, or halothane in oxygen. All exposures were conducted at the onset of light. Results Mice in all three anesthetized groups exhibited a significant doubling of REM sleep during the first 6 h of the dark phase of the circadian schedule, whereas only mice exposed to halothane displayed a significant increase in nonrapid eye movement sleep that peaked at 152% of baseline. Conclusion REM sleep rebound after exposure to volatile anesthetics suggests that these volatile anesthetics do not fully substitute for natural sleep. This result contrasts with the published actions of propofol for which no REM sleep rebound occurred.

scholarly journals Targeted memory reactivation in human REM sleep elicits recurrent, temporally compressed reactivation

2021 ◽  
Author(s):  
Mahmoud E. A. Abdellahi ◽  
Anne C. M. Koopman ◽  
Matthias S. Treder ◽  
Penelope A. Lewis
Keyword(s):  
Machine Learning ◽  
Eye Movement ◽  
Performance Improvement ◽  
Rem Sleep ◽  
Strong Evidence ◽  
Nrem Sleep ◽  
Theta Activity ◽  
Rapid Eye Movement ◽  
Memory Reactivation ◽  
Machine Learning Classifiers

AbstractMemories are reactivated during non-rapid eye movement (NREM) sleep, but the question of whether equivalent reactivation also occurs in rapid eye movement (REM) sleep is hotly debated. To examine this, we used a technique called targeted memory reactivation (TMR) in which sounds are paired with learned material in wake, and then re-presented in subsequent sleep to trigger reactivation. We then used machine learning classifiers to identify TMR-induced reactivation in REM. The reactivation we measured was temporally compressed by approximately five times during REM compared to wakeful performance of the task, and often occurred twice after a single TMR cue. Reactivation strength positively predicted overnight performance improvement and was only apparent in trials with high theta activity. These findings provide strong evidence for memory reactivation in human REM sleep after TMR as well as an initial characterisation of this reactivation.

scholarly journals Regulation of REM Sleep by Inhibitory Neurons in the Dorsomedial Medulla

2020 ◽  
Author(s):  
Joseph A. Stucynski ◽  
Amanda L. Schott ◽  
Justin Baik ◽  
Shinjae Chung ◽  
Franz Weber
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Sleep Stages ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Brain Rhythms ◽  
Slow Activity ◽  
Raphé Nuclei

ABSTRACTThe two major stages of mammalian sleep – rapid eye movement sleep (REMs) and non-REM sleep (NREMs) – are characterized by distinct brain rhythms ranging from millisecond to minute-long (infraslow) oscillations. The mechanisms controlling transitions between sleep stages and how they are synchronized with infraslow rhythms remain poorly understood. Using opto- and chemogenetic manipulation, we show that GABAergic neurons in the dorsomedial medulla (dmM) promote the initiation and maintenance of REMs, in part through their projections to the dorsal and median raphe nuclei. Fiber photometry revealed that dmM GABAergic neurons are strongly activated during REMs. During NREMs, their activity fluctuated in close synchrony with infraslow oscillations in the spindle band of the electroencephalogram, and the phase of this rhythm modulated the latency of optogenetically induced REMs episodes. Thus, dmM inhibitory neurons powerfully promote REMs, and their slow activity fluctuations may coordinate transitions from NREMs to REMs with infraslow brain rhythms.

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