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Revue Neurologique Oct 2023All our lives, we alternate between wakefulness and sleep with direct consequences on our ability to interact with our environment, the dynamics and contents of our... (Review)
Review
All our lives, we alternate between wakefulness and sleep with direct consequences on our ability to interact with our environment, the dynamics and contents of our subjective experience, and our brain activity. Consequently, sleep has been extensively characterised in terms of behavioural, phenomenological, and physiological changes, the latter constituting the gold standard of sleep research. The common view is thus that sleep represents a collection of discrete states with distinct neurophysiological signatures. However, recent findings challenge such a monolithic view of sleep. Indeed, there can be sharp discrepancies in time and space in the activity displayed by different brain regions or networks, making it difficult to assign a global vigilance state to such a mosaic of contrasted dynamics. Viewing sleep as a multidimensional continuum rather than a succession of non-overlapping and mutually exclusive states could account for these local aspects of sleep. Moving away from the focus on sleep states, sleep can also be investigated through the brain processes that are present in sleep, if not necessarily specific to sleep. This focus on processes rather than states allows to see sleep for what it does rather than what it is, avoiding some of the limitations of the state perspective and providing a powerful heuristic to understand sleep. Indeed, what is sleep if not a process itself that makes up wake up every morning with a brain cleaner, leaner and less cluttered.
Topics: Humans; Sleep; Brain; Wakefulness; Electroencephalography
PubMed: 37625978
DOI: 10.1016/j.neurol.2023.08.007 -
Sleep Medicine Reviews Apr 2012The locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. State-dependent neuronal discharge activity of locus coeruleus... (Review)
Review
The locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. State-dependent neuronal discharge activity of locus coeruleus noradrenergic neurons has long-suggested a role of this system in the induction of an alert waking state. Work over the past two decades provides unambiguous evidence that the locus coeruleus, and likely other noradrenergic nuclei, exert potent wake-promoting actions via an activation of noradrenergic β- and α₁-receptors located within multiple subcortical structures, including the general regions of the medial septal area, the medial preoptic area and, most recently, the lateral hypothalamus. Conversely, global blockade of β- and α₁-receptors or suppression of norepinephrine release results in profound sedation. The wake-promoting action of central noradrenergic neurotransmission has clinical implications for treatment of sleep/arousal disorders, such as insomnia and narcolepsy, and clinical conditions associated with excessive arousal, such as post-traumatic stress disorder.
Topics: Adrenergic Neurons; Animals; Arousal; Humans; Locus Coeruleus; Norepinephrine; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, beta; Septal Nuclei; Wakefulness
PubMed: 22296742
DOI: 10.1016/j.smrv.2011.12.003 -
Neuropsychobiology 2015During the last few decades, much knowledge has been gained about sleep being a heterogeneous condition with several distinct sleep stages that represent fundamentally... (Review)
Review
During the last few decades, much knowledge has been gained about sleep being a heterogeneous condition with several distinct sleep stages that represent fundamentally different physiological states. The same applies for the wake state which also comprises distinct global functional states (called vigilance stages). However, various terms and concepts have been introduced describing different aspects of wakefulness, and accordingly several methods of assessment exist, e.g. sleep laboratory assessments (Multiple Sleep Latency Test, Maintenance of Wakefulness Test), questionnaires (Epworth Sleepiness Scale, Karolinska Sleepiness Scale), behavioural tasks (Psychomotor Vigilance Test) or electroencephalography (EEG)-based assessments (Alpha Attenuation Test, Karolinska Drowsiness Test). Furthermore, several theoretical concepts about the regulation of sleep and wakefulness have been put forward, and physiological correlates have been identified. Most relevant for healthy functioning is the regulation of brain arousal and the adaption of wakefulness to the environmental and situational needs so that the optimal balance between energy conservation and responsiveness can be obtained. Since one approach to the assessment of brain arousal regulation is the classification of EEG vigilance stages, a computer-based algorithm (Vigilance Algorithm Leipzig) has been introduced, allowing classification of EEG vigilance stages in EEG recordings under resting conditions. The time course of EEG vigilance stages in EEGs of 15-20 min duration allows estimation of the individual arousal regulation (hyperstable, adaptive, or unstable vigilance pattern). The vigilance model of affective disorders and attention-deficit/hyperactivity disorder links a disturbed arousal regulation to the pathogenesis of psychiatric disorders and accordingly helps to explain and possibly also predict treatment effects of pharmacological and non-pharmacological interventions for these conditions.
Topics: Animals; Arousal; Brain; Electroencephalography; Humans; Mental Disorders; Sleep; Wakefulness
PubMed: 26901462
DOI: 10.1159/000439384 -
Molecular Psychiatry Jul 2021The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits...
The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep-wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D and D/D receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light-dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.
Topics: Animals; Basal Forebrain; GABAergic Neurons; Mice; Motivation; Ventral Tegmental Area; Wakefulness
PubMed: 33057171
DOI: 10.1038/s41380-020-00906-0 -
The Journal of Neuroscience : the... Oct 2022Sustained attention describes our ability to keep a constant focus on a given task. This ability is modulated by our physiological state of arousal. Although lapses of... (Randomized Controlled Trial)
Randomized Controlled Trial
Sustained attention describes our ability to keep a constant focus on a given task. This ability is modulated by our physiological state of arousal. Although lapses of sustained attention have been linked with dysregulations of arousal, the underlying physiological mechanisms remain unclear. An emerging body of work proposes that the intrusion during wakefulness of sleep-like slow waves, a marker of the transition toward sleep, could mechanistically account for attentional lapses. This study aimed to expose, via pharmacological manipulations of the monoamine system, the relationship between the occurrence of sleep-like slow waves and the behavioral consequences of sustained attention failures. In a double-blind, randomized-control trial, 32 healthy human male participants received methylphenidate, atomoxetine, citalopram or placebo during four separate experimental sessions. During each session, electroencephalography (EEG) was used to measure neural activity while participants completed a visual task requiring sustained attention. Methylphenidate, which increases wake-promoting dopamine and noradrenaline across cortical and subcortical areas, improved behavioral performance whereas atomoxetine, which increases dopamine and noradrenaline predominantly over frontal cortices, led to more impulsive responses. Additionally, citalopram, which increases sleep-promoting serotonin, led to more missed trials. Based on EEG recording, citalopram was also associated with an increase in sleep-like slow waves. Importantly, compared with a classical marker of arousal such as α power, only slow waves differentially predicted both misses and faster responses in a region-specific fashion. These results suggest that a decrease in arousal can lead to local sleep intrusions during wakefulness which could be mechanistically linked to impulsivity and sluggishness. We investigated whether the modulation of attention and arousal could not only share the same neuromodulatory pathways but also rely on similar neuronal mechanisms; for example, the intrusion of sleep-like activity within wakefulness. To do so, we pharmacologically manipulated noradrenaline, dopamine, and serotonin in a four-arm, randomized, placebo-controlled trial and examined the consequences on behavioral and electroencephalography (EEG) indices of attention and arousal. We showed that sleep-like slow waves can predict opposite behavioral signatures: impulsivity and sluggishness. Slow waves may be a candidate mechanism for the occurrence of attentional lapses since the relationship between slow-wave occurrence and performance is region-specific and the consequences of these local sleep intrusions are in line with the cognitive functions carried by the underlying brain regions.
Topics: Male; Humans; Citalopram; Dopamine; Atomoxetine Hydrochloride; Serotonin; Sleep; Wakefulness; Electroencephalography; Attention; Norepinephrine; Methylphenidate
PubMed: 36109167
DOI: 10.1523/JNEUROSCI.0836-22.2022 -
Nature Communications Apr 2023Despite extensive research on astrocytic Ca in synaptic transmission, its contribution to the modulation of sensory transmission during different brain states remains...
Despite extensive research on astrocytic Ca in synaptic transmission, its contribution to the modulation of sensory transmission during different brain states remains largely unknown. Here, by using two-photon microscopy and whole-cell recordings, we show two distinct astrocytic Ca signals in the murine barrel cortex: a small, long-lasting Ca increase during sleep and a large, widespread but short-lasting Ca spike when aroused. The large Ca wave in aroused mice was inositol trisphosphate (IP3)-dependent, evoked by the locus coeruleus-norepinephrine system, and enhanced sensory input, contributing to reliable sensory transmission. However, the small Ca transient was IP3-independent and contributed to decreased extracellular K, hyperpolarization of the neurons, and suppression of sensory transmission. These events respond to different pharmacological inputs and contribute to distinct sleep and arousal functions by modulating the efficacy of sensory transmission. Together, our data demonstrate an important function for astrocytes in sleep and arousal states via astrocytic Ca waves.
Topics: Mice; Animals; Wakefulness; Astrocytes; Calcium Signaling; Arousal; Sleep
PubMed: 37069258
DOI: 10.1038/s41467-023-37974-z -
The Journal of Neuroscience : the... Feb 2023Arousal state affects neural activity and vascular dynamics in the cortex, with sleep associated with large changes in the local field potential and increases in...
Arousal state affects neural activity and vascular dynamics in the cortex, with sleep associated with large changes in the local field potential and increases in cortical blood flow. We investigated the relationship between pupil diameter and blink rate with neural activity and blood volume in the somatosensory cortex in male and female unanesthetized, head-fixed mice. We monitored these variables while the mice were awake, during periods of rapid eye movement (REM), and non-rapid eye movement (NREM) sleep. Pupil diameter was smaller during sleep than in the awake state. Changes in pupil diameter were coherent with both gamma-band power and blood volume in the somatosensory cortex, but the strength and sign of this relationship varied with arousal state. We observed a strong negative correlation between pupil diameter and both gamma-band power and blood volume during periods of awake rest and NREM sleep, although the correlations between pupil diameter and these signals became positive during periods of alertness, active whisking, and REM. Blinking was associated with increases in arousal and decreases in blood volume when the mouse was asleep. Bilateral coherence in gamma-band power and in blood volume dropped following awake blinking, indicating a reset of neural and vascular activity. Using only eye metrics (pupil diameter and eye motion), we could determine the arousal state of the mouse ('Awake,' 'NREM,' 'REM') with >90% accuracy with a 5 s resolution. There is a strong relationship between pupil diameter and hemodynamics signals in mice, reflecting the pronounced effects of arousal on cerebrovascular dynamics. Determining arousal state is a critical component of any neuroscience experiment. Pupil diameter and blinking are influenced by arousal state, as are hemodynamics signals in the cortex. We investigated the relationship between cortical hemodynamics and pupil diameter and found that pupil diameter was strongly related to the blood volume in the cortex. Mice were more likely to be awake after blinking than before, and blinking resets neural activity. Pupil diameter and eye motion can be used as a reliable, noninvasive indicator of arousal state. As mice transition from wake to sleep and back again over a timescale of seconds, monitoring pupil diameter and eye motion permits the noninvasive detection of sleep events during behavioral or resting-state experiments.
Topics: Male; Female; Mice; Animals; Blinking; Pupil; Arousal; Wakefulness; Hemodynamics; Electroencephalography
PubMed: 36517240
DOI: 10.1523/JNEUROSCI.1244-22.2022 -
Sleep Apr 2017The complexity of the brain is yielding to technology. In the area of sleep neurobiology, conventional neuroscience tools such as lesions, cell recordings, c-Fos, and... (Review)
Review
The complexity of the brain is yielding to technology. In the area of sleep neurobiology, conventional neuroscience tools such as lesions, cell recordings, c-Fos, and axon-tracing methodologies have been instrumental in identifying the complex and intermingled populations of sleep- and arousal-promoting neurons that orchestrate and generate wakefulness, NREM, and REM sleep. In the last decade, new technologies such as optogenetics, chemogenetics, and the CRISPR-Cas system have begun to transform how biologists understand the finer details associated with sleep-wake regulation. These additions to the neuroscience toolkit are helping to identify how discrete populations of brain cells function to trigger and shape the timing and transition into and out of different sleep-wake states, and how glia partner with neurons to regulate sleep. Here, we detail how some of the newest technologies are being applied to understand the neural circuits underlying sleep and wake.
Topics: Animals; Brain; CRISPR-Cas Systems; Humans; Neuroglia; Neurons; Neurosciences; Optogenetics; Sleep; Sleep, REM; Wakefulness
PubMed: 28329204
DOI: 10.1093/sleep/zsx032 -
Experimental Physiology Jan 1996This review has described the many behavioural and arousal-related influences on breathing and the extent of these influences in humans. The chief examples have included... (Review)
Review
This review has described the many behavioural and arousal-related influences on breathing and the extent of these influences in humans. The chief examples have included the effect on breathing of altered mental activity, wakefulness and sleep, and learned respiratory responses. Determining the precise neurological mechanisms underlying these effects represents a difficult challenge to respiratory physiologists who seek to understand the respiratory control system of awake behaving humans. Nevertheless, insight into the various forebrain and brainstem inputs to respiratory muscles has been gained by studies of breathing during particular behaviours (when either voluntary or reflex breathing predominates) or in particular neurological patients (in whom either voluntary or reflex breathing is defective). With developments in brain imaging techniques, such as functional magnetic resonance imaging, it may soon be possible to determine more precisely the various anatomical sources and timing of the motor commands to breathe during different behaviours, states of arousal and sleep.
Topics: Arousal; Behavior; Drive; Humans; Nervous System Physiological Phenomena; Respiration; Sleep; Wakefulness
PubMed: 8869137
DOI: 10.1113/expphysiol.1996.sp003911 -
Cell Reports Jan 2024Arousal and awareness are two components of consciousness whose neural mechanisms remain unclear. Spontaneous peaks of global (brain-wide)...
Arousal and awareness are two components of consciousness whose neural mechanisms remain unclear. Spontaneous peaks of global (brain-wide) blood-oxygenation-level-dependent (BOLD) signal have been found to be sensitive to changes in arousal. By contrasting BOLD signals at different arousal levels, we find decreased activation of the ventral posterolateral nucleus (VPL) during transient peaks in the global signal in low arousal and awareness states (non-rapid eye movement sleep and anesthesia) compared to wakefulness and in eyes-closed compared to eyes-open conditions in healthy awake individuals. Intriguingly, VPL-global co-activation remains high in patients with unresponsive wakefulness syndrome (UWS), who exhibit high arousal without awareness, while it reduces in rapid eye movement sleep, a state characterized by low arousal but high awareness. Furthermore, lower co-activation is found in individuals during N3 sleep compared to patients with UWS. These results demonstrate that co-activation of VPL and global activity is critical to arousal but not to awareness.
Topics: Humans; Ventral Thalamic Nuclei; Sleep; Arousal; Wakefulness; Brain; Electroencephalography
PubMed: 38159279
DOI: 10.1016/j.celrep.2023.113633