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Current Biology : CB Jan 2022The 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...
The 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 in mice, 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 their activity is strongly increased during REMs and fluctuates during NREMs in close synchrony with infraslow oscillations in the sleep spindle band of the electroencephalogram. The phase of this rhythm influenced the latency and probability with which dmM activation induced REMs. Thus, dmM inhibitory neurons strongly promote REMs, and their slow activity fluctuations may coordinate the timing of REMs episodes with infraslow brain rhythms.
Topics: Animals; Electroencephalography; GABAergic Neurons; Mammals; Mice; Sleep; Sleep Stages; Sleep, REM; Wakefulness
PubMed: 34735794
DOI: 10.1016/j.cub.2021.10.030 -
Nature Communications Jun 2023Mammalian sleep has been implicated in maintaining a healthy extracellular environment in the brain. During wakefulness, neuronal activity leads to the accumulation of...
Mammalian sleep has been implicated in maintaining a healthy extracellular environment in the brain. During wakefulness, neuronal activity leads to the accumulation of toxic proteins, which the glymphatic system is thought to clear by flushing cerebral spinal fluid (CSF) through the brain. In mice, this process occurs during non-rapid eye movement (NREM) sleep. In humans, ventricular CSF flow has also been shown to increase during NREM sleep, as visualized using functional magnetic resonance imaging (fMRI). The link between sleep and CSF flow has not been studied in birds before. Using fMRI of naturally sleeping pigeons, we show that REM sleep, a paradoxical state with wake-like brain activity, is accompanied by the activation of brain regions involved in processing visual information, including optic flow during flight. We further demonstrate that ventricular CSF flow increases during NREM sleep, relative to wakefulness, but drops sharply during REM sleep. Consequently, functions linked to brain activation during REM sleep might come at the expense of waste clearance during NREM sleep.
Topics: Humans; Mice; Animals; Sleep, REM; Brain; Sleep; Wakefulness; Columbidae; Electroencephalography; Mammals
PubMed: 37277328
DOI: 10.1038/s41467-023-38669-1 -
Proceedings of the National Academy of... Oct 2023Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye...
Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in "orexin intact" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.
Topics: Animals; Mice; Cataplexy; Narcolepsy; Orexins; Sleep; Sleep, REM; Wakefulness
PubMed: 37796986
DOI: 10.1073/pnas.2301951120 -
Journal of Neurology, Neurosurgery, and... Jul 2020The rapid eye movement sleep behavioural disorder (RBD) population is an ideal study population for testing disease-modifying treatments for synucleinopathies, since RBD... (Review)
Review
The rapid eye movement sleep behavioural disorder (RBD) population is an ideal study population for testing disease-modifying treatments for synucleinopathies, since RBD represents an early prodromal stage of synucleinopathy when neuropathology may be more responsive to treatment. While clonazepam and melatonin are most commonly used as symptomatic treatments for RBD, clinical trials of symptomatic treatments are also needed to identify evidence-based treatments. A comprehensive framework for both disease-modifying and symptomatic treatment trials in RBD is described, including potential treatments in the pipeline, cost-effective participant recruitment and selection, study design, outcomes and dissemination of results. For disease-modifying treatment clinical trials, the recommended primary outcome is phenoconversion to an overt synucleinopathy, and stratification features should be used to select a study population at high risk of phenoconversion, to enable more rapid clinical trials. For symptomatic treatment clinical trials, objective polysomnogram-based measurement of RBD-related movements and vocalisations should be the primary outcome measure, rather than subjective scales or diaries. Mobile technology to enable objective measurement of RBD episodes in the ambulatory setting, and advances in imaging, biofluid, tissue, and neurophysiological biomarkers of synucleinopathies, will enable more efficient clinical trials but are still in development. Increasing awareness of RBD among the general public and medical community coupled with timely diagnosis of these diseases will facilitate progress in the development of therapeutics for RBD and associated neurodegenerative disorders.
Topics: Clinical Trials as Topic; Humans; REM Sleep Behavior Disorder; Research Design; Sleep, REM
PubMed: 32404379
DOI: 10.1136/jnnp-2020-322875 -
Proceedings of the National Academy of... May 2023Rapid eye movement sleep (REM) is believed to have a binary temporal structure with "phasic" and "tonic" microstates, characterized by motoric activity versus...
Rapid eye movement sleep (REM) is believed to have a binary temporal structure with "phasic" and "tonic" microstates, characterized by motoric activity versus quiescence, respectively. However, we observed in mice that the frequency of theta activity (a marker of rodent REM) fluctuates in a nonbinary fashion, with the extremes of that fluctuation correlating with phasic-type and tonic-type facial motricity. Thus, phasic and tonic REM may instead represent ends of a continuum. These cycles of brain physiology and facial movement occurred at 0.01 to 0.06 Hz, or infraslow frequencies, and affected cross-frequency coupling and neuronal activity in the neocortex, suggesting network functional impact. We then analyzed human data and observed that humans also demonstrate nonbinary phasic/tonic microstates, with continuous 0.01 to 0.04-Hz respiratory rate cycles matching the incidence of eye movements. These fundamental properties of REM can yield insights into our understanding of sleep health.
Topics: Humans; Animals; Mice; Sleep, REM; Sleep; Eye Movements; Neocortex
PubMed: 37094161
DOI: 10.1073/pnas.2213438120 -
Sleep May 2021It has been reported that adult ostriches displayed the longest episodes of rapid eye movement (REM) sleep (up to 5 min) and more REM sleep (24% of the nighttime) than...
It has been reported that adult ostriches displayed the longest episodes of rapid eye movement (REM) sleep (up to 5 min) and more REM sleep (24% of the nighttime) than any other bird species. If the mammalian ontogenetic trend exists in the ostrich, then the amounts of REM and the duration of sleep episodes in young ostriches may be greater than those reported in adults. We investigated sleep in 1.5-3.5 month old ostrich chicks. Recordings were conducted during nighttime (20:00-08:00), the main sleep period in ostriches, which are diurnal. The polygrams were scored in 4-s epochs for waking, non-rapid eye movement (NREM) sleep and REM sleep, as in other bird studies. REM sleep in ostrich chicks occurred during both cortical EEG activation and during slow waves, as was described in adult ostriches. The chicks spent 69.3% ± 1.5% of the night in NREM sleep. REM sleep occupied 14.1% ± 1.8% of the night or 16.8% ± 2.0% of nighttime sleep. Episodes of REM sleep lasted on average 10 ± 1 s and ranged between 4 and 40 s. Therefore, the total amount and duration of REM sleep episodes in ostrich chicks were substantially smaller than reported in adult ostriches while the amounts of NREM sleep did not greatly differ. The developmental profile of REM sleep ontogenesis in the ostrich may be remarkably different from what has been reported in all studied mammals and birds.
Topics: Animals; Electroencephalography; Sleep; Sleep, REM; Sleep, Slow-Wave; Struthioniformes
PubMed: 33249508
DOI: 10.1093/sleep/zsaa259 -
Biological Research 2007With 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... (Review)
Review
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.
Topics: Brain; Humans; Neuronal Plasticity; Sleep, REM
PubMed: 18575679
DOI: No ID Found -
Current Neurology and Neuroscience... Feb 2022Rapid eye movement (REM) sleep behaviour disorder (RBD) is considered the expression of the initial neurodegenerative process underlying synucleinopathies and... (Review)
Review
PURPOSE OF REVIEW
Rapid eye movement (REM) sleep behaviour disorder (RBD) is considered the expression of the initial neurodegenerative process underlying synucleinopathies and constitutes the most important marker of their prodromal phase. This article reviews recent research from longitudinal research studies in isolated RBD (iRBD) aiming to describe the most promising progression biomarkers of iRBD and to delineate the current knowledge on the level of prediction of future outcome in iRBD patients at diagnosis.
RECENT FINDINGS
Longitudinal studies revealed the potential value of a variety of biomarkers, including clinical markers of motor, autonomic, cognitive, and olfactory symptoms, neurophysiological markers such as REM sleep without atonia and electroencephalography, genetic and epigenetic markers, cerebrospinal fluid and serum markers, and neuroimaging markers to track the progression and predict phenoconversion. To-date the most promising neuroimaging biomarker in iRBD to aid the prediction of phenoconversion is striatal presynaptic striatal dopaminergic dysfunction. There is a variety of potential biomarkers for monitoring disease progression and predicting iRBD conversion into synucleinopathies. A combined multimodal biomarker model could offer a more sensitive and specific tool. Further longitudinal studies are warranted to iRBD as a high-risk population for early neuroprotective interventions and disease-modifying therapies.
Topics: Biomarkers; Humans; Neuroimaging; REM Sleep Behavior Disorder; Sleep, REM; Synucleinopathies
PubMed: 35274191
DOI: 10.1007/s11910-022-01171-0 -
Journal of Sleep Research Aug 2022This manuscript presents an overview of REM sleep behaviour disorder (RBD) with a special focus on European contributions. After an introduction examining the history of... (Review)
Review
This manuscript presents an overview of REM sleep behaviour disorder (RBD) with a special focus on European contributions. After an introduction examining the history of the disorder, we address the pathophysiological and clinical aspects, as well as the diagnostic issues. Further, implications of RBD diagnosis and biomarkers are discussed. Contributions of European researchers to this field are highlighted.
Topics: Humans; Polysomnography; REM Sleep Behavior Disorder; Sleep, REM
PubMed: 35470494
DOI: 10.1111/jsr.13612 -
Annual Review of Vision Science Sep 2019Recent data have shown that sleep plays a beneficial role for cognitive functions such as declarative memory consolidation and perceptual learning. In this article, we... (Review)
Review
Recent data have shown that sleep plays a beneficial role for cognitive functions such as declarative memory consolidation and perceptual learning. In this article, we review recent findings on the role of sleep in promoting adaptive visual response changes in the lateral geniculate nucleus and primary visual cortex following novel visual experiences. We discuss these findings in the context of what is currently known about how sleep affects the activity and function of thalamocortical circuits and current hypotheses regarding how sleep facilitates synaptic plasticity.
Topics: Animals; Geniculate Bodies; Humans; Neuronal Plasticity; Sleep, REM; Thalamic Nuclei; Visual Cortex; Visual Pathways
PubMed: 31283451
DOI: 10.1146/annurev-vision-091718-014715