Role Of Rapid Eye Movement Sleep Research Articles

Howard P. Roffwarg: sleep pioneer, legend, and ontogenetic hypothesis author.

Narrated in this article are accounts of the many contributions Howard P. Roffwarg, MD, made to the field of sleep research and sleep medicine across his entire professional career as a student, a mentor, a leader in the Sleep Research Society, a sleep medicine clinician, and a scientist who performed experimental investigations in humans and animals. Dr Roffwarg was the originator of what is known as the "Ontogenetic Hypothesis" of sleep. His research over many years on physiology has contributed greatly to much of the experimental support substantiating a role for rapid eye-movement sleep (REMS) in the early development of the brain. Though much is still unknown, the Ontogenetic Hypothesis, still to this day, inspires many neuroscientists in their investigations. These studies have demonstrated roles for both REMS and NREMS in development as well as on brain function throughout his life span. Dr Howard P. Roffwarg, is one of the legends in the field of sleep research.

Increased Rapid Eye Movement Sleep Is Associated With a Reduced Risk of Heart Failure in Middle-Aged and Older Adults.

ObjectivesRapid eye movement (REM) sleep is closely related to all-cause mortality. The aim of this study is to explore the role of REM sleep on the incident heart failure (HF).MethodsWe selected 4490 participants (2480 women and 2010 men; mean age, 63.2 ± 11.0 years) from the Sleep Heart Health Study. HF was identified as the first occurrence during a mean follow-up period of 10.9 years. REM sleep including percentage of REM sleep and total REM sleep time were monitored using in-home polysomnography at baseline. Multivariable Cox regression analysis was utilized to explore the relationship between REM sleep and HF.ResultsIn total, 436 (9.7%) cases of HF were observed during the entire follow-up period. After adjusting for potential covariates, an increased percentage of REM sleep (per 5%) was independently associated with a reduced incidence of HF [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.82–0.94, P < 0.001]. A similar result was also found between total REM sleep time (increased per 5 min) and incident HF (HR 0.97, 95% CI 0.95–0.99, P < 0.001). Moreover, the fourth quartile of both percentage of REM sleep (HR 0.65, 95% CI 0.48–0.88, P = 0.005) and total REM sleep time (HR 0.64, 95% CI 0.45–0.90, P = 0.010) had lower risk of incident HF when compared with the first quartile.ConclusionAn increased percentage of REM sleep and total REM sleep time were associated with a reduced risk of HF. REM sleep may be a predictor of the incident HF.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT00005275].

REM Sleep Deprivation Alters Learning-Induced Cell Proliferation and Generation of Newborn Young Neurons in the Dentate Gyrus of the Dorsal Hippocampus.

The hippocampus-dependent "trace-appetitive conditioning task" increases cell proliferation and the generation of newborn young neurons. Evidence suggests that adult hippocampal neurogenesis and rapid eye movement (REM) sleep play an essential role in memory consolidation. On the other hand, REM sleep deprivation (REM-SD) induces detrimental effects on training-induced cell proliferation in the hippocampus's dentate gyrus (DG). Nonetheless, the role of REM sleep in the trace-appetitive memory and fate determination of the newly proliferated cells is not known. Here, we have studied the following: (I) the effects of 24 h of REM-SD (soon after training) on trace- and delay-appetitive memory and cell proliferation in the adult DG and (II) the effects of chronic (96 h) REM-SD (3 days after the training, the period in which newly generated cells progressed toward the neuronal lineage) on trace-appetitive memory and the generation of newborn young neurons. We used a modified multiple platform method for the selective REM-SD without altering non-REM (NREM) sleep. We found that 24 h of REM-SD, soon after trace-conditioning, impaired the trace-appetitive memory and the training-induced cell proliferation. Nevertheless, 96 h of REM-SD (3 days after the training) did not impair trace memory. Interestingly, 96 h of REM-SD altered the generation of newborn young neurons. These results suggest that REM sleep plays an essential role in training-induced cell proliferation and the fate determination of the newly generated cells toward the neuronal lineage.

Sparse Activity of Hippocampal Adult-Born Neurons during REM Sleep Is Necessary for Memory Consolidation

The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown. Here, we investigate whether young ABN activity contributes to memory consolidation during sleep using Ca2+ imaging in freely moving mice. We found that contextual fear learning recruits a population of young ABNs that are reactivated during subsequent REM sleep against a backdrop of overall reduced ABN activity. Optogenetic silencing of this sparse ABN activity during REM sleep alters the structural remodeling of spines on ABN dendrites and impairs memory consolidation. These findings provide a causal link between ABN activity during REM sleep and memory consolidation.

Remembering specific features of emotional events across time: The role of REM sleep and prefrontal theta oscillations.

When an episode of emotional significance is encountered, it often results in the formation of a highly resistant memory representation that is easily retrieved for many succeeding years. Recent research shows that beyond generic consolidation processes, rapid eye movement (REM) sleep importantly contributes to this effect. However, the boundary conditions of consolidation processes during REM sleep, specifically whether these extend to source memory, have not been examined extensively. The current study tested the effects of putative consolidation processes emerging during REM sleep and slow wave sleep (SWS) on item and source memory of negative and neutral images, respectively. Results demonstrate superior emotional relative to neutral item memory retention after both late night REM sleep and early night SWS. Emotional source memory, on the other hand, exhibited an attenuated decline following late night REM sleep, whereas neutral source memory was selectively preserved across early night SWS. This pattern of results suggests a selective preservation of emotional source memory during REM sleep that is functionally dissociable from SWS-dependent reprocessing of neutral source memory. This was further substantiated by a neurophysiological dissociation: Postsleep emotional source memory was selectively correlated with frontal theta lateralization (REM sleep), whereas postsleep neutral item memory was correlated with SWS spindle power. As such, the present results contribute to a more comprehensive characterization of sleep-related consolidation mechanisms underlying emotional and neutral memory retention. Subsidiary analysis of emotional reactivity to previously encoded material revealed an enhancing rather than attenuating effect of late night REM sleep on emotional responses.

REM sleep selectively prunes and maintains new synapses in development and learning.

The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.

Sex differences in sleep-dependent perceptual learning.

Sex differences in learning and memory suggest differences between men and women in mechanisms of neural plasticity. Such differences have been reported in a variety of explicit memory tasks, but implicit memory has not been studied in this context. We investigated differences between men and women in offline consolidation of perceptual learning (PL) of motion direction discrimination. Initially, discrimination thresholds were measured for two opposite directions of motion, followed by approximately 40 minutes of training on one of the directions. During a post-training consolidation period, subjects either took a nap or remained awake. Thresholds were then reassessed for both directions of motion. We found that rapid eye movement (REM) sleep facilitates consolidation of PL but that the pattern of specificity in the REM condition differed between men and women. PL for men whose naps contained REM sleep was highly specific to the trained direction of motion, whereas REM sleep in women resulted in generalized learning to the untrained direction as well as to a novel direction that was not previously tested. Moreover, for subjects in the REM condition, men exhibited greater PL than women for the trained direction. Our findings provide the first evidence of sex differences in the magnitude and specificity of PL and in the role of REM sleep in implicit learning. Our results have important implications for optimization of educational and training strategies designed for males and females.

Declarative memory consolidation during the first night in a sleep lab: The role of REM sleep and cortisol

While the consolidation of declarative memory is supported by slow wave sleep (SWS) in healthy subjects, it has been shown to be associated with rapid eye movement (REM) sleep in patients with insomnia. Sleep during a subject's first night in an unfamiliar environment is often disturbed, and this so-called first-night effect (FNE) has often been used as a model of transient insomnia. Additionally, sleeping for the first time in an unfamiliar environment can lead to increased cortisol secretion, and declarative memory consolidation likely depends on low cortisol levels, especially during the early part of the night. Accounting for intersubject variability in the FNE, we examined the relationship between sleep stages, cortisol secretion and declarative memory performance in 27 healthy young men. Declarative memory performance improved significantly after sleep. Whereas memory performance during the learning session and retrieval testing was strongly associated with cortisol secretion, the overnight gain was not. Post hoc analyses indicated that the overnight gain appears to be modulated by the extent of the FNE: a significant overnight improvement in memory performance was found only in subjects with a weak FNE (n=12). In these subjects, no association was found between any sleep stage and the improvement observed in their memory performance. In subjects with a strong FNE (n=12), however, the overnight change in memory performance was associated with the proportion of REM sleep and the total number of REMs. Disturbed sleep in an unfamiliar environment therefore appears to affect the memory consolidation process.

The role of REM sleep in the processing of emotional memories: Evidence from behavior and event-related potentials

Emotional memories are vividly remembered for the long-term. Rapid eye movement (REM) sleep has been repeatedly proposed to support the superior retention of emotional memories. However, its exact contribution and, specifically, whether its effect is mainly on the consolidation of the contents or the processing of the affective component of emotional memories is not clear. Here, we investigated the effects of sleep rich in slow wave sleep (SWS) or REM sleep on the consolidation of emotional pictures and the accompanying changes in affective tone, using event-related potentials (ERPs) together with subjective ratings of valence and arousal. Sixteen healthy, young men learned 50 negative and 50 neutral pictures before 3-h retention sleep intervals that were filled with either SWS-rich early or REM sleep-rich late nocturnal sleep. In accordance with our hypothesis, recognition was better for emotional pictures than neutral pictures after REM compared to SWS-rich sleep. This emotional enhancement after REM-rich sleep expressed itself in an increased late positive potential of the ERP over the frontal cortex 300–500ms after stimulus onset for correctly classified old emotional pictures compared with new emotional and neutral pictures. Valence and arousal ratings of emotional pictures were not differentially affected by REM or SWS-rich sleep after learning. Our results corroborate that REM sleep contributes to the consolidation of emotional contents in memory, but suggest that the affective tone is preserved rather than reduced by the processing of emotional memories during REM sleep.

A Role for REM Sleep in Recalibrating the Sensitivity of the Human Brain to Specific Emotions

Although the impact of sleep on cognitive function is increasingly well established, the role of sleep in modulating affective brain processes remains largely uncharacterized. Using a face recognition task, here we demonstrate an amplified reactivity to anger and fear emotions across the day, without sleep. However, an intervening nap blocked and even reversed this negative emotional reactivity to anger and fear while conversely enhancing ratings of positive (happy) expressions. Most interestingly, only those subjects who obtained rapid eye movement (REM) sleep displayed this remodulation of affective reactivity for the latter 2 emotion categories. Together, these results suggest that the evaluation of specific human emotions is not static across a daytime waking interval, showing a progressive reactivity toward threat-related negative expressions. However, an episode of sleep can reverse this predisposition, with REM sleep depotentiating negative reactivity toward fearful expressions while concomitantly facilitating recognition and ratings of reward-relevant positive expressions. These findings support the view that sleep, and specifically REM neurophysiology, may represent an important factor governing the optimal homeostasis of emotional brain regulation.

Sleep in brain development.

With the discovery of rapid eye movement (REM) sleep, sleep was no longer considered a homogeneous state of passive rest for the brain. On the contrary, sleep, and especially REM sleep, appeared as an active condition of intense cerebral activity. The fact that we get large amounts of sleep in early life suggested that sleep may play a role in brain maturation. This idea has been investigated for many years through a large number of animal and human studies, but evidence remains fragmented. The hypothesis proposed was that REM sleep would provide an endogenous source of activation, possibly critical for structural maturation of the central nervous system. This proposal led to a series of experiments looking at the role of REM sleep in brain development. In particular, the influence of sleep in developing the visual system has been highlighted. More recently, non-REM (NREM) sleep state has become a major focus of attention. The current data underscore the importance of both REM sleep and NREM sleep states in normal synaptic development and lend support to their functional roles in brain maturation. Both sleep states appear to be important for neuronal development, but the corresponding contribution is likely to be different.

Sleep in brain development

With the discovery of rapid eye movement (REM) sleep, sleep was no longer considered a homogeneous state of passive rest for the brain. On the contrary, sleep, and especially REM sleep, appeared as an active condition of intense cerebral activity. The fact that we get large amounts of sleep in early life suggested that sleep may play a role in brain maturation. This idea has been investigated for many years through a large number of animal and human studies, but evidence remains fragmented. The hypothesis proposed was that REM sleep would provide an endogenous source of activation, possibly critical for structural maturation of the central nervous system. This proposal led to a series of experiments looking at the role of REM sleep in brain development. In particular, the influence of sleep in developing the visual system has been highlighted. More recently, non-REM (NREM) sleep state has become a major focus of attention. The current data underscore the importance of both REM sleep and NREM sleep states in normal synaptic development and lend support to their functional roles in brain maturation. Both sleep states appear to be important for neuronal development, but the corresponding contribution is likely to be different.

Rapid eye movement (rem) sleep deprivation: effect on acid mucopolysaccharides in rat brain.

The effect of rapid eye movement (REM) sleep deprivation on the total content and proportion of different mucopolysaccharides (AMPS) containing uronic acid in rat brain was studied. REM sleep deprivation was induced by the water tank methods. Five experimental groups of animals were used: control, stressed, REM sleep deprived, post-stress sleeping and post-deprivation sleeping rats. No changes of AMPS were observed in any of the experimental groups when the whole brain was analysed. A significant increase of AMPS was found in the cerebral hemispheres of stressed and REM deprived rats. A significant decrease of AMPS was observed in the cerebellum and brain stem. A further increase of AMPS was found in the cerebral hemispheres after the rebound of REM sleep following its deprivation, and after the recovery sleep following the stress. A significant increase of AMPS was found in the brain stem of rats allowed to recuperate after REM deprivation or stress as compared with the stressed and REM deprived animals. Recovery sleep induced a significant increase of AMPS in the cerebellum in previously stressed rats, while previously REM deprived rats exhibited a further decrease of AMPS from control values. The possible functional meaning of these results is discussed in relation to the role of REM sleep in protein synthesis and learning and memory processes. Intriguing, well-controlled positive findings and the fact that no experimental design is known where stress is minimal while REM deprivation is 100 per cent, justify and encourage continued efforts in studying the biochemical state of the brain during sleep and/or its alterations.