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Science (New York, N.Y.) Oct 2023Neural substrates of wakefulness, rapid eye movement sleep (REMS), and non-REMS (NREMS) in the mammalian hypothalamus overlap both anatomically and functionally with... (Review)
Review
Neural substrates of wakefulness, rapid eye movement sleep (REMS), and non-REMS (NREMS) in the mammalian hypothalamus overlap both anatomically and functionally with cellular networks that support physiological and behavioral homeostasis. Here, we review the roles of sleep neurons of the hypothalamus in the homeostatic control of thermoregulation or goal-oriented behaviors during wakefulness. We address how hypothalamic circuits involved in opposing behaviors such as core body temperature and sleep compute conflicting information and provide a coherent vigilance state. Finally, we highlight some of the key unresolved questions and challenges, and the promise of a more granular view of the cellular and molecular diversity underlying the integrative role of the hypothalamus in physiological and behavioral homeostasis.
Topics: Animals; Body Temperature Regulation; Electroencephalography; Hypothalamus; Sleep, REM; Wakefulness; Humans; Neurons; Sleep, Slow-Wave
PubMed: 37883555
DOI: 10.1126/science.adh8285 -
Neuron Oct 2023The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it...
The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATm) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATm population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATm neurons or multiple downstream pathways. In awake mice, ATm activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.
Topics: Mice; Animals; Arousal; Thalamus; Wakefulness; Neurons; Synaptic Transmission
PubMed: 37557180
DOI: 10.1016/j.neuron.2023.07.007 -
Cell Dec 2023Conscious perception is greatly diminished during sleep, but the underlying circuit mechanism is poorly understood. We show that cortical ignition-a brain process shown...
Conscious perception is greatly diminished during sleep, but the underlying circuit mechanism is poorly understood. We show that cortical ignition-a brain process shown to be associated with conscious awareness in humans and non-human primates-is strongly suppressed during non-rapid-eye-movement (NREM) sleep in mice due to reduced cholinergic modulation and rapid inhibition of cortical responses. Brain-wide functional ultrasound imaging and cell-type-specific calcium imaging combined with optogenetics showed that activity propagation from visual to frontal cortex is markedly reduced during NREM sleep due to strong inhibition of frontal pyramidal neurons. Chemogenetic activation and inactivation of basal forebrain cholinergic neurons powerfully increased and decreased visual-to-frontal activity propagation, respectively. Furthermore, although multiple subtypes of dendrite-targeting GABAergic interneurons in the frontal cortex are more active during wakefulness, soma-targeting parvalbumin-expressing interneurons are more active during sleep. Chemogenetic manipulation of parvalbumin interneurons showed that sleep/wake-dependent cortical ignition is strongly modulated by perisomatic inhibition of pyramidal neurons.
Topics: Animals; Mice; Cholinergic Neurons; Electroencephalography; Frontal Lobe; Parvalbumins; Sleep; Wakefulness
PubMed: 38070510
DOI: 10.1016/j.cell.2023.11.012 -
Anesthesiology Feb 2024
Topics: Humans; Neuromuscular Blockade; Anesthesiologists; Wakefulness; Anesthetics
PubMed: 38193736
DOI: 10.1097/ALN.0000000000004808 -
Nature Reviews. Neuroscience Jan 2024Sleep is considered essential for the brain and body. A predominant concept is that sleep is regulated by circadian rhythmicity and sleep homeostasis, processes that... (Review)
Review
Sleep is considered essential for the brain and body. A predominant concept is that sleep is regulated by circadian rhythmicity and sleep homeostasis, processes that were posited to be functionally and mechanistically separate. Here we review and re-evaluate this concept and its assumptions using findings from recent human and rodent studies. Alterations in genes that are central to circadian rhythmicity affect not only sleep timing but also putative markers of sleep homeostasis such as electroencephalogram slow-wave activity (SWA). Perturbations of sleep change the rhythmicity in the expression of core clock genes in tissues outside the central clock. The dynamics of recovery from sleep loss vary across sleep variables: SWA and immediate early genes show an early response, but the recovery of non-rapid eye movement and rapid eye movement sleep follows slower time courses. Changes in the expression of many genes in response to sleep perturbations outlast the effects on SWA and time spent asleep. These findings are difficult to reconcile with the notion that circadian- and sleep-wake-driven processes are mutually independent and that the dynamics of sleep homeostasis are reflected in a single variable. Further understanding of how both sleep and circadian rhythmicity contribute to the homeostasis of essential physiological variables may benefit from the assessment of multiple sleep and molecular variables over longer time scales.
Topics: Humans; Wakefulness; Sleep; Circadian Rhythm; Sleep, REM; Electroencephalography; Homeostasis
PubMed: 38040815
DOI: 10.1038/s41583-023-00764-z -
Continuum (Minneapolis, Minn.) Aug 2023Non-rapid eye movement (non-REM) parasomnias are common across the lifespan. This article describes the manifestations, diagnosis, and management of non-REM parasomnias...
OBJECTIVE
Non-rapid eye movement (non-REM) parasomnias are common across the lifespan. This article describes the manifestations, diagnosis, and management of non-REM parasomnias in adults and discusses the social implications of these conditions.
LATEST DEVELOPMENTS
Non-REM parasomnias represent a hybrid state of wakefulness and sleep, often triggered by events that increase the frequency of arousals or make it more difficult to fully arouse from sleep. Sleep deprivation, certain medications, and untreated obstructive sleep apnea are known to provoke parasomnias, particularly in those who are genetically predisposed. Non-REM parasomnias include disorders of arousal (ie, sleepwalking, sleep terrors, and confusional arousals), sleep-related eating disorder, and exploding head syndrome. Clinical overlap exists between sleep-related eating disorder and disorders of arousal, suggesting that sleep-related eating disorder may be a fourth disorder of arousal or a manifestation of sleepwalking. Exploding head syndrome is a unique parasomnia of uncertain etiology.
ESSENTIAL POINTS
Non-REM parasomnias can range from minor nuisances to severe, life-altering events. While some patients with non-REM parasomnia experience significant consequences during sleep, wakefulness, or both, non-REM parasomnias do not pose a major risk to most patients. For all patients with non-REM parasomnias, safety should be explicitly discussed and addressed. Nonpharmacologic treatment should be prioritized, as increasing total sleep time, avoiding triggering substances, and treating comorbid sleep disorders is often sufficient for the management of non-REM parasomnias. If symptoms persist despite these interventions, treatment with clonazepam or other medications can be considered.
Topics: Adult; Humans; Somnambulism; Parasomnias; Sleep; Wakefulness; Sleep Duration
PubMed: 37590825
DOI: 10.1212/CON.0000000000001261 -
Trends in Neurosciences Apr 2024Sleep is crucial for many vital functions and has been extensively studied. By contrast, the sleep-onset period (SOP), often portrayed as a mere prelude to sleep, has... (Review)
Review
Sleep is crucial for many vital functions and has been extensively studied. By contrast, the sleep-onset period (SOP), often portrayed as a mere prelude to sleep, has been largely overlooked and remains poorly characterized. Recent findings, however, have reignited interest in this transitional period and have shed light on its neural mechanisms, cognitive dynamics, and clinical implications. This review synthesizes the existing knowledge about the SOP in humans. We first examine the current definition of the SOP and its limits, and consider the dynamic and complex electrophysiological changes that accompany the descent to sleep. We then describe the interplay between internal and external processing during the wake-to-sleep transition. Finally, we discuss the putative cognitive benefits of the SOP and identify novel directions to better diagnose sleep-onset disorders.
Topics: Humans; Electroencephalography; Wakefulness; Sleep
PubMed: 38519370
DOI: 10.1016/j.tins.2024.02.002 -
Pharmacology & Therapeutics Sep 2023Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABA receptor. This underscores the significance... (Review)
Review
Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABA receptor. This underscores the significance of GABAergic neurotransmission in both the initiation and maintenance of sleep. Nevertheless, an increasing body of evidence substantiates the notion that GABA-mediated neurotransmission also assumes a vital role in promoting wakefulness in specific neuronal circuits. Despite the longstanding belief in the pivotal function of GABA in regulating the sleep-wake cycle, there exists a dearth of comprehensive documentation regarding the specific regions within the central nervous system where GABAergic neurons are crucial for these functions. In this review, we delve into the involvement of GABAergic neurons in the regulation of sleep-wake cycles, with particular focus on those located in the preoptic area (POA) and ventral tegmental area (VTA). Recent research, including our own, has further underscored the importance of GABAergic neurotransmission in these areas for the regulation of sleep-wake cycles.
Topics: Humans; Sleep; Wakefulness; GABAergic Neurons; Central Nervous System; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 37541595
DOI: 10.1016/j.pharmthera.2023.108505 -
Neuron Jul 2023The classic view of sleep and vigilance states is a global stationary perspective driven by the interaction between neuromodulators and thalamocortical systems.... (Review)
Review
The classic view of sleep and vigilance states is a global stationary perspective driven by the interaction between neuromodulators and thalamocortical systems. However, recent data are challenging this view by demonstrating that vigilance states are highly dynamic and regionally complex. Spatially, sleep- and wake-like states often co-occur across distinct brain regions, as in unihemispheric sleep, local sleep in wakefulness, and during development. Temporally, dynamic switching prevails around state transitions, during extended wakefulness, and in fragmented sleep. This knowledge, together with methods monitoring brain activity across multiple regions simultaneously at millisecond resolution with cell-type specificity, is rapidly shifting how we consider vigilance states. A new perspective incorporating multiple spatial and temporal scales may have important implications for considering the governing neuromodulatory mechanisms, the functional roles of vigilance states, and their behavioral manifestations. A modular and dynamic view highlights novel avenues for finer spatiotemporal interventions to improve sleep function.
Topics: Wakefulness; Sleep; Brain; Electroencephalography
PubMed: 37148873
DOI: 10.1016/j.neuron.2023.04.012 -
Sleep Medicine Clinics Mar 2024Recurrent isolated sleep paralysis has a 7.6% lifetime prevalence of at least one episode in the general population. Episodes resolve spontaneously and are benign. Sleep... (Review)
Review
Recurrent isolated sleep paralysis has a 7.6% lifetime prevalence of at least one episode in the general population. Episodes resolve spontaneously and are benign. Sleep paralysis represents a dissociate state, with persistence of the rapid eye movement (REM)-sleep muscle atonia in the waking state. The intrusion of alpha electroencephalogram into REM sleep is followed by an arousal response and then by persistence of REM atonia into wakefulness. Predisposing factors include irregular sleep-wake schedules, sleep deprivation, and jetlag. No drug treatment is required. Patients should be informed about sleep hygiene. Cognitive behavioral therapy may be useful in cases accompanied by anxiety and frightening hallucinations.
Topics: Humans; Sleep Paralysis; Sleep, REM; Sleep; Wakefulness; Arousal
PubMed: 38368058
DOI: 10.1016/j.jsmc.2023.10.006