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Current Neuropharmacology 2022General anesthesia has been successfully used in clinics for over 170 years, but its mechanisms of effect remain unclear. Behaviorally, general anesthesia is similar to... (Review)
Review
General anesthesia has been successfully used in clinics for over 170 years, but its mechanisms of effect remain unclear. Behaviorally, general anesthesia is similar to sleep as it produces a reversible transition between wakefulness and the state of being unaware of one's surroundings. A discussion regarding the common circuits of sleep and general anesthesia has been ongoing as an increasing number of sleep-arousal regulatory nuclei are reported to participate in the consciousness shift occurring during general anesthesia. Recently, with progress in research technology, both positive and negative evidence for overlapping neural circuits between sleep and general anesthesia has emerged. This article provides a review of the latest evidence on the neural substrates for sleep and general anesthesia regulation by comparing the roles of pivotal nuclei in sleep and anesthesia.
Topics: Anesthesia, General; Humans; Sleep; Wakefulness
PubMed: 34906058
DOI: 10.2174/1570159X19666211214144639 -
The Journal of Clinical Psychiatry Aug 2015Research into the sleep-wake cycle has provided new treatment targets for patients with insomnia as well as a better understanding of how medications affect sleep... (Review)
Review
Research into the sleep-wake cycle has provided new treatment targets for patients with insomnia as well as a better understanding of how medications affect sleep processes. Current insomnia medications, including benzodiazepines and nonbenzodiazepines, focus on enhancing sleep-promoting systems through broad antagonism of GABA. Other medications that promote sleep by blocking wake-promoting systems include antidepressants, antipsychotics, and antihistamines, but adverse effects and nonspecific therapeutic effects limit their use. New and emerging insomnia medications are focusing on blocking wake-promoting systems via more selective antagonism of orexin, serotonin, and norepinephrine. These medications may offer improved efficacy with fewer adverse effects.
Topics: Humans; Sleep; Sleep Initiation and Maintenance Disorders; Wakefulness
PubMed: 26335094
DOI: 10.4088/JCP.14046tx2c -
BMC Neurology Jul 2023The wakefulness-sleep cycle sets the pace of our life. Sleep research examines the transition between wakefulness and sleep, its hormonal regulation, and its...
The wakefulness-sleep cycle sets the pace of our life. Sleep research examines the transition between wakefulness and sleep, its hormonal regulation, and its pathological disruption. Understanding sleep mechanisms would improve quality-of-life well beyond sleep itself. To this aim, we invite contributions for the Collection "sleep physiology and circadian rhythms".
Topics: Humans; Sleep; Circadian Rhythm; Wakefulness; Quality of Life
PubMed: 37507691
DOI: 10.1186/s12883-023-03330-3 -
Neuron May 2022Functional ultrasound (fUS) is an emerging technique that measures blood flow to report brain activity. In this issue of Neuron, Nunez-Elizalde et al. (2022) use...
Functional ultrasound (fUS) is an emerging technique that measures blood flow to report brain activity. In this issue of Neuron, Nunez-Elizalde et al. (2022) use simultaneous electrophysiological and fUS measurements to quantify the relationship between firing and fUS signals in awake mice.
Topics: Animals; Electrophysiological Phenomena; Mice; Neurons; Sound; Wakefulness
PubMed: 35588709
DOI: 10.1016/j.neuron.2022.04.025 -
Current Biology : CB Apr 2023Waking behaviors such as sitting or standing require suitable levels of muscle tone. But it is unclear how arousal and motor circuits communicate with one another so...
Waking behaviors such as sitting or standing require suitable levels of muscle tone. But it is unclear how arousal and motor circuits communicate with one another so that appropriate motor tone occurs during wakefulness. Cataplexy is a peculiar condition in which muscle tone is involuntarily lost during normal periods of wakefulness. Cataplexy therefore provides a unique opportunity for identifying the signaling mechanisms that synchronize motor and arousal behaviors. Cataplexy occurs when hypothalamic orexin neurons are lost in narcolepsy; however, it is unclear if motor-arousal decoupling in cataplexy is directly or indirectly caused by orexin cell loss. Here, we used genomic, proteomic, chemogenetic, electrophysiological, and behavioral assays to determine if grafting orexin cells into the brain of cataplectic (i.e., orexin) mice restores normal motor-arousal behaviors by preventing cataplexy. First, we engineered immortalized orexin cells and found that they not only produce and release orexin but also exhibit a gene profile that mimics native orexin neurons. Second, we show that engineered orexin cells thrive and integrate into host tissue when transplanted into the brain of mice. Next, we found that grafting only 200-300 orexin cells into the dorsal raphe nucleus-a region densely innervated by native orexin neurons-reduces cataplexy. Last, we show that real-time chemogenetic activation of orexin cells restores motor-arousal synchrony by preventing cataplexy. We suggest that orexin signaling is critical for arousal-motor synchrony during wakefulness and that the dorsal raphe plays a pivotal role in coupling arousal and motor behaviors.
Topics: Mice; Animals; Cataplexy; Orexins; Proteomics; Arousal; Wakefulness; Dorsal Raphe Nucleus; Cell Transplantation
PubMed: 37044089
DOI: 10.1016/j.cub.2023.03.077 -
Nature Jul 2023While sleeping, many vertebrate groups alternate between at least two sleep stages: rapid eye movement and slow wave sleep, in part characterized by wake-like and... (Comparative Study)
Comparative Study
While sleeping, many vertebrate groups alternate between at least two sleep stages: rapid eye movement and slow wave sleep, in part characterized by wake-like and synchronous brain activity, respectively. Here we delineate neural and behavioural correlates of two stages of sleep in octopuses, marine invertebrates that evolutionarily diverged from vertebrates roughly 550 million years ago (ref. ) and have independently evolved large brains and behavioural sophistication. 'Quiet' sleep in octopuses is rhythmically interrupted by approximately 60-s bouts of pronounced body movements and rapid changes in skin patterning and texture. We show that these bouts are homeostatically regulated, rapidly reversible and come with increased arousal threshold, representing a distinct 'active' sleep stage. Computational analysis of active sleep skin patterning reveals diverse dynamics through a set of patterns conserved across octopuses and strongly resembling those seen while awake. High-density electrophysiological recordings from the central brain reveal that the local field potential (LFP) activity during active sleep resembles that of waking. LFP activity differs across brain regions, with the strongest activity during active sleep seen in the superior frontal and vertical lobes, anatomically connected regions associated with learning and memory function. During quiet sleep, these regions are relatively silent but generate LFP oscillations resembling mammalian sleep spindles in frequency and duration. The range of similarities with vertebrates indicates that aspects of two-stage sleep in octopuses may represent convergent features of complex cognition.
Topics: Animals; Mammals; Octopodiformes; Sleep; Sleep, REM; Wakefulness; Integumentary System; Movement; Time Factors; Local Field Potential Measurement; Learning; Central Nervous System; Arousal
PubMed: 37380770
DOI: 10.1038/s41586-023-06203-4 -
Revista de Neurologia Mar 2017Distributed neural networks in the brain sustain generation of wakefulness and two sleep states: non-REM sleep and REM sleep. These three behavioral states are jointly... (Review)
Review
Distributed neural networks in the brain sustain generation of wakefulness and two sleep states: non-REM sleep and REM sleep. These three behavioral states are jointly ingrained in a rhythmic sequence that constitutes the sleep-wakefulness cycle. This paper reviews and updates knowledge about the involvement of the histaminergic system in sleep-wakefulness cycle organization. Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, but are the source of a widespread projection system to many brain regions. Histamine neurons are active during waking, especially with high attention need, and remain silent in both non-REM and REM sleep. There have been described four metabotropic histamine receptors, of which H1R, H2R and H3R are present in the nervous system. H1R and H2R are mainly postsynaptic heteroreceptors, whereas H3R is thought to be mostly a presynaptic auto- and hetero-receptor. Histaminergic neurons are excited by hypocretinergic neurons and most of the arousing hypocretin effects are thought to depend on histaminergic actions. Interactions among histaminergic axons and cholinergic nuclei within forebrain and brainstem are particularly important for cortical activation. In contrast, histaminergic tuberomammillary neurons, similarly to other aminergic neurons in locus coeruleus or dorsal raphe nucleus, are inhibited by non-REM sleep-promoting neurons of the preoptic region. Further inhibitory actions on histamine neurons come from adenosine release on tuberomammillary region. Finally, histaminergic neurons inhibit REM-on hypothalamic neurons containing melanine-concentrating hormone, thus supporting a permissive role of tuberomammillary nucleus in REM sleep. Actually, knockout mice for histidine decarboxylase, the enzyme synthetizing histamine, show a significant REM sleep increase.
Topics: Animals; Histamine; Humans; Mice; Neurons; Receptors, Histamine; Sleep; Wakefulness
PubMed: 28272728
DOI: No ID Found -
Nature Communications Feb 2022Consciousness can be defined by two components: arousal (wakefulness) and awareness (subjective experience). However, neurophysiological consciousness metrics able to...
Consciousness can be defined by two components: arousal (wakefulness) and awareness (subjective experience). However, neurophysiological consciousness metrics able to disentangle between these components have not been reported. Here, we propose an explainable consciousness indicator (ECI) using deep learning to disentangle the components of consciousness. We employ electroencephalographic (EEG) responses to transcranial magnetic stimulation under various conditions, including sleep (n = 6), general anesthesia (n = 16), and severe brain injury (n = 34). We also test our framework using resting-state EEG under general anesthesia (n = 15) and severe brain injury (n = 34). ECI simultaneously quantifies arousal and awareness under physiological, pharmacological, and pathological conditions. Particularly, ketamine-induced anesthesia and rapid eye movement sleep with low arousal and high awareness are clearly distinguished from other states. In addition, parietal regions appear most relevant for quantifying arousal and awareness. This indicator provides insights into the neural correlates of altered states of consciousness.
Topics: Anesthesia, General; Arousal; Brain Injuries; Consciousness; Deep Learning; Electroencephalography; Humans; Wakefulness
PubMed: 35217645
DOI: 10.1038/s41467-022-28451-0 -
Scientific Reports Mar 2022In a recent experiment, we showed that horses are sensitive to pet-directed speech (PDS), a kind of speech used to talk to companion animals that is characterized by...
In a recent experiment, we showed that horses are sensitive to pet-directed speech (PDS), a kind of speech used to talk to companion animals that is characterized by high pitch and wide pitch variations. When talked to in PDS rather than adult-directed speech (ADS), horses reacted more favorably during grooming and in a pointing task. However, the mechanism behind their response remains unclear: does PDS draw horses' attention and arouse them, or does it make their emotional state more positive? In this study, we used an innovative paradigm in which female horses watched videos of humans speaking in PDS or ADS to better understand this phenomenon. Horses reacted differently to the videos of PDS and ADS: they were significantly more attentive and their heart rates increased significantly more during PDS than during ADS. We found no difference in the expressions of negative or positive emotional states during PDS and ADS videos. Thus, we confirm that horses' perception of humans can be studied by means of video projections, and we conclude that PDS attracts attention and has an arousing effect in horses, with consequences on the use of PDS in daily interactions with them.
Topics: Animals; Attention; Emotions; Female; Grooming; Horses; Humans; Speech; Wakefulness
PubMed: 35277552
DOI: 10.1038/s41598-022-08109-z -
Neuroscience and Biobehavioral Reviews Sep 2016Why do animals and humans do anything at all? Arousal is the most powerful and essential function of the brain, a continuous function that accounts for the ability of... (Review)
Review
Why do animals and humans do anything at all? Arousal is the most powerful and essential function of the brain, a continuous function that accounts for the ability of animals and humans to respond to stimuli in the environment by producing muscular responses. Following decades of psychological, neurophysiological and molecular investigations, generalized CNS arousal can now be analyzed using approaches usually applied to physical systems. The concept of "criticality" is a state that illustrates an advantage for arousal systems poised near a phase transition. This property provides speed and sensitivity and facilitates the transition of the system into different brain states, especially as the brain crosses a phase transition from less aroused to more aroused states. In summary, concepts derived from applied mathematics of physical systems will now find their application in this area of neuroscience, the neurobiology of CNS arousal.
Topics: Animals; Arousal; Brain; Central Nervous System; Humans; Neurobiology; Vertebrates; Wakefulness
PubMed: 27216213
DOI: 10.1016/j.neubiorev.2016.05.014