Phase-locked auditory stimulation of theta oscillations during rapid eye movement sleep

Abstract Auditory closed-loop stimulation is a non-invasive technique that has been widely used to augment slow oscillations during non-rapid eye movement sleep. Based on the principles of closed-loop stimulation, we developed a novel protocol for manipulating theta activity (3–7 Hz) in rapid eye movement (REM) sleep. Sixteen healthy young adults were studied in two overnight conditions: Stimulation and Sham. In the Stimulation condition, 1 s of 5 Hz amplitude-modulated white noise was delivered upon detection of two supra-threshold theta cycles throughout REM sleep. In the Sham condition, corresponding time points were marked but no stimulation was delivered. Auditory stimulation entrained EEG activity to 5 Hz and evoked a brief (~0.5 s) increase in theta power. Interestingly, this initial theta surge was immediately followed by a prolonged (~3 s) period of theta suppression. Stimulation also induced a prolonged (~2 s) increase in beta power. Our results provide the first demonstration that the REM sleep theta rhythm can be manipulated in a targeted manner via auditory stimulation. Accordingly, auditory stimulation might offer a fruitful avenue for investigating REM sleep electrophysiology and its relationship to behavior.

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Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep

Scientific Reports ◽

10.1038/s41598-020-67392-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Elena Krugliakova ◽

Carina Volk ◽

Valeria Jaramillo ◽

Georgia Sousouri ◽

Reto Huber

Keyword(s):

Eye Movement ◽

Closed Loop ◽

Auditory Stimulation ◽

Rapid Eye Movement ◽

Rapid Eye Movement Sleep ◽

Frequency Coupling ◽

Cross Frequency Coupling

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

Journal of Neurophysiology ◽

10.1152/jn.00993.2002 ◽

2003 ◽

Vol 90 (2) ◽

pp. 938-945 ◽

Cited By ~ 62

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.

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Dream Recall upon Awakening from Non-Rapid Eye Movement Sleep in Older Adults: Electrophysiological Pattern and Qualitative Features

Brain Sciences ◽

10.3390/brainsci10060343 ◽

2020 ◽

Vol 10 (6) ◽

pp. 343 ◽

Cited By ~ 3

Author(s):

Serena Scarpelli ◽

Aurora D’Atri ◽

Chiara Bartolacci ◽

Maurizio Gorgoni ◽

Anastasia Mangiaruga ◽

...

Keyword(s):

Eye Movement ◽

Sleep Stage ◽

Nrem Sleep ◽

Rapid Eye Movement ◽

Rapid Eye Movement Sleep ◽

Dream Recall ◽

Cortical Arousal ◽

Beta Power ◽

Dream Report

Several findings support the activation hypothesis, positing that cortical arousal promotes dream recall (DR). However, most studies have been carried out on young participants, while the electrophysiological (EEG) correlates of DR in older people are still mostly unknown. We aimed to test the activation hypothesis on 20 elders, focusing on the Non-Rapid Eye Movement (NREM) sleep stage. All the subjects underwent polysomnography, and a dream report was collected upon their awakening from NREM sleep. Nine subjects were recallers (RECs) and 11 were non-RECs (NRECs). The delta and beta EEG activity of the last 5 min and the total NREM sleep was calculated by Fast Fourier Transform. Statistical comparisons (RECs vs. NRECs) revealed no differences in the last 5 min of sleep. Significant differences were found in the total NREM sleep: the RECs showed lower delta power over the parietal areas than the NRECs. Consistently, statistical comparisons on the activation index (delta/beta power) revealed that RECs showed a higher level of arousal in the fronto-temporal and parieto-occipital regions than NRECs. Both visual vividness and dream length are positively related to the level of activation. Overall, our results are consistent with the view that dreaming and the storage of oneiric contents depend on the level of arousal during sleep, highlighting a crucial role of the temporo-parietal-occipital zone.

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

Journal of Applied Physiology ◽

10.1152/jappl.1991.71.4.1201 ◽

1991 ◽

Vol 71 (4) ◽

pp. 1201-1215 ◽

Cited By ~ 10

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.

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

Mathematical Modelling and Analysis ◽

10.3846/13926292.2016.1247302 ◽

2016 ◽

Vol 21 (6) ◽

pp. 794-810 ◽

Cited By ~ 1

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.

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

Anesthesiology ◽

10.1097/aln.0b013e31822ddd72 ◽

2011 ◽

Vol 115 (4) ◽

pp. 702-712 ◽

Cited By ~ 37

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.

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Regulation of REM Sleep by Inhibitory Neurons in the Dorsomedial Medulla

10.1101/2020.11.30.405530 ◽

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

10.1101/460600 ◽

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.

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