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Molecular Circuits Regulating Sleep and Wakeful Consciousness
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Molecular Circuits Regulating Sleep and Wakeful Consciousness

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 29556

Special Issue Editors

Prof. Dr. Michael Lazarus

E-Mail Website
Guest Editor
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba 305-8575, Japan
Interests: sleep; motivation; arousal; sleep function; neural circuits; opto-biology/pharmacology
Special Issues, Collections and Topics in MDPI journals
Dr. Wang Yi-Qun

E-Mail Website
Guest Editor
Department of Pharmacology, School of Basic Medical Sciences of Fudan University, Fudan University, Shanghai, China
Interests: REM sleep regulation; REM sleep function; sleep-related olfaction

Special Issue Information

Dear Colleagues,

The sleep field has recently witnessed an exponential increase in the understanding of brain circuitries regulating sleep/wake behavior. However, it remains puzzling that brain circuits’ switching occurs within seconds, while sleep regulation (i.e., the process of the accumulation/dissipation of sleep need) takes hours. The teleological problem of sleep regulation and function arises from the presumption of sleep’s evolution from a default state of waking. Humans are likely biased towards this presumption by the egocentricity of waking consciousness. The goal of the Special Issue is to gather original research and review articles relevant to the control of non-rapid eye movement (non-REM), REM sleep, or wakeful consciousness. We are especially seeking contributions that shed light on mechanisms underlying key aspects of the sleep states, such as sleep need; the circadian, ultradian, or behavioral gating of sleep; and REM sleep homeostasis. We are open to articles that use innovative techniques to study the detailed circuit and synaptic basis of sleep/wake control, for example, electrophysiological recording or imaging used in combination with pharmacologic or the genetically driven perturbation of defined sets of neurons or glial cells in all animals that have the ability to sleep or exhibit a sleep-like behavior. We also welcome studies on the molecular profiling of sleep and wake states or the crosstalk between sleep and peripheral physiological systems (e.g., immune system or metabolism), as well as studies about physical and chemical factors that influence sleep and wakefulness.

Prof. Dr. Michael Lazarus
Dr. Wang Yi-Qun
Guest Editors

Manuscript Submission Information

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Keywords

  • sleep
  • sleep function
  • glia–neuron interaction
  • molecular circuits
  • sleep homeostasis
  • arousal
  • slow-wave sleep
  • REM sleep
  • physical or chemical sleep/wake factors

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Published Papers (5 papers)

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Research

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25 pages, 4383 KiB  
Article
Role of Dorsomedial Hypothalamus GABAergic Neurons in Sleep–Wake States in Response to Changes in Ambient Temperature in Mice
by Lei Li, Meng-Qi Zhang, Xiao Sun, Wen-Ying Liu, Zhi-Li Huang and Yi-Qun Wang
Int. J. Mol. Sci. 2022, 23(3), 1270; https://doi.org/10.3390/ijms23031270 - 23 Jan 2022
Cited by 8 | Viewed by 3774
Abstract
Good sleep quality is essential for maintaining the body’s attention during wakefulness, which is easily affected by external factors such as an ambient temperature. However, the mechanism by which an ambient temperature influences sleep–wake behaviors remains unclear. The dorsomedial hypothalamus (DMH) has been [...] Read more.
Good sleep quality is essential for maintaining the body’s attention during wakefulness, which is easily affected by external factors such as an ambient temperature. However, the mechanism by which an ambient temperature influences sleep–wake behaviors remains unclear. The dorsomedial hypothalamus (DMH) has been reported to be involved in thermoregulation. It also receives projection from the preoptic area, which is an important region for sleep and energy homeostasis and the suprachiasmatic nucleus—a main control area of the clock rhythm. Therefore, we hypothesized that the DMH plays an important role in the regulation of sleep related to ambient temperatures. In this study, we found that cold exposure (24/20/16/12 °C) increased wakefulness and decreased non–rapid eye movement (NREM) sleep, while warm exposure (32/36/40/44 °C) increased NREM sleep and decreased wakefulness compared to 28 °C conditions in wild-type mice. Then, using non-specific and specific apoptosis, we found that lesions of whole DMH neurons and DMH γ–aminobutyric acid (GABA)-ergic neurons induced by caspase-3 virus aggravated the fluctuation of core body temperature after warm exposure and attenuated the change in sleep–wake behaviors during cold and warm exposure. However, chemogenetic activation or inhibition of DMH GABAergic neurons did not affect the sleep–wake cycle. Collectively, our findings reveal an essential role of DMH GABAergic neurons in the regulation of sleep–wake behaviors elicited by a change in ambient temperature. Full article
(This article belongs to the Special Issue Molecular Circuits Regulating Sleep and Wakeful Consciousness)
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Review

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23 pages, 1117 KiB  
Review
When the Locus Coeruleus Speaks Up in Sleep: Recent Insights, Emerging Perspectives
by Alejandro Osorio-Forero, Najma Cherrad, Lila Banterle, Laura M. J. Fernandez and Anita Lüthi
Int. J. Mol. Sci. 2022, 23(9), 5028; https://doi.org/10.3390/ijms23095028 - 30 Apr 2022
Cited by 35 | Viewed by 6628
Abstract
For decades, numerous seminal studies have built our understanding of the locus coeruleus (LC), the vertebrate brain’s principal noradrenergic system. Containing a numerically small but broadly efferent cell population, the LC provides brain-wide noradrenergic modulation that optimizes network function in the context of [...] Read more.
For decades, numerous seminal studies have built our understanding of the locus coeruleus (LC), the vertebrate brain’s principal noradrenergic system. Containing a numerically small but broadly efferent cell population, the LC provides brain-wide noradrenergic modulation that optimizes network function in the context of attentive and flexible interaction with the sensory environment. This review turns attention to the LC’s roles during sleep. We show that these roles go beyond down-scaled versions of the ones in wakefulness. Novel dynamic assessments of noradrenaline signaling and LC activity uncover a rich diversity of activity patterns that establish the LC as an integral portion of sleep regulation and function. The LC could be involved in beneficial functions for the sleeping brain, and even minute alterations in its functionality may prove quintessential in sleep disorders. Full article
(This article belongs to the Special Issue Molecular Circuits Regulating Sleep and Wakeful Consciousness)
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17 pages, 1585 KiB  
Review
Roles of Neuropeptides in Sleep–Wake Regulation
by Yi-Chen Shen, Xiao Sun, Lei Li, Hu-Yunlong Zhang, Zhi-Li Huang and Yi-Qun Wang
Int. J. Mol. Sci. 2022, 23(9), 4599; https://doi.org/10.3390/ijms23094599 - 21 Apr 2022
Cited by 13 | Viewed by 4890
Abstract
Sleep and wakefulness are basic behavioral states that require coordination between several brain regions, and they involve multiple neurochemical systems, including neuropeptides. Neuropeptides are a group of peptides produced by neurons and neuroendocrine cells of the central nervous system. Like traditional neurotransmitters, neuropeptides [...] Read more.
Sleep and wakefulness are basic behavioral states that require coordination between several brain regions, and they involve multiple neurochemical systems, including neuropeptides. Neuropeptides are a group of peptides produced by neurons and neuroendocrine cells of the central nervous system. Like traditional neurotransmitters, neuropeptides can bind to specific surface receptors and subsequently regulate neuronal activities. For example, orexin is a crucial component for the maintenance of wakefulness and the suppression of rapid eye movement (REM) sleep. In addition to orexin, melanin-concentrating hormone, and galanin may promote REM sleep. These results suggest that neuropeptides play an important role in sleep–wake regulation. These neuropeptides can be divided into three categories according to their effects on sleep–wake behaviors in rodents and humans. (i) Galanin, melanin-concentrating hormone, and vasoactive intestinal polypeptide are sleep-promoting peptides. It is also noticeable that vasoactive intestinal polypeptide particularly increases REM sleep. (ii) Orexin and neuropeptide S have been shown to induce wakefulness. (iii) Neuropeptide Y and substance P may have a bidirectional function as they can produce both arousal and sleep-inducing effects. This review will introduce the distribution of various neuropeptides in the brain and summarize the roles of different neuropeptides in sleep–wake regulation. We aim to lay the foundation for future studies to uncover the mechanisms that underlie the initiation, maintenance, and end of sleep–wake states. Full article
(This article belongs to the Special Issue Molecular Circuits Regulating Sleep and Wakeful Consciousness)
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16 pages, 752 KiB  
Review
The Sleep-Promoting Ventrolateral Preoptic Nucleus: What Have We Learned over the Past 25 Years?
by Elda Arrigoni and Patrick M. Fuller
Int. J. Mol. Sci. 2022, 23(6), 2905; https://doi.org/10.3390/ijms23062905 - 8 Mar 2022
Cited by 20 | Viewed by 5446
Abstract
For over a century, the role of the preoptic hypothalamus and adjacent basal forebrain in sleep–wake regulation has been recognized. However, for years, the identity and location of sleep- and wake-promoting neurons in this region remained largely unresolved. Twenty-five years ago, Saper and [...] Read more.
For over a century, the role of the preoptic hypothalamus and adjacent basal forebrain in sleep–wake regulation has been recognized. However, for years, the identity and location of sleep- and wake-promoting neurons in this region remained largely unresolved. Twenty-five years ago, Saper and colleagues uncovered a small collection of sleep-active neurons in the ventrolateral preoptic nucleus (VLPO) of the preoptic hypothalamus, and since this seminal discovery the VLPO has been intensively investigated by labs around the world, including our own. Herein, we first review the history of the preoptic area, with an emphasis on the VLPO in sleep–wake control. We then attempt to synthesize our current understanding of the circuit, cellular and synaptic bases by which the VLPO both regulates and is itself regulated, in order to exert a powerful control over behavioral state, as well as examining data suggesting an involvement of the VLPO in other physiological processes. Full article
(This article belongs to the Special Issue Molecular Circuits Regulating Sleep and Wakeful Consciousness)
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21 pages, 5207 KiB  
Review
Allosteric Modulation of Adenosine A2A Receptors as a New Therapeutic Avenue
by Mustafa Korkutata, Lokesh Agrawal and Michael Lazarus
Int. J. Mol. Sci. 2022, 23(4), 2101; https://doi.org/10.3390/ijms23042101 - 14 Feb 2022
Cited by 10 | Viewed by 7219
Abstract
The therapeutic potential of targeting adenosine A2A receptors (A2ARs) is immense due to their broad expression in the body and central nervous system. The role of A2ARs in cardiovascular function, inflammation, sleep/wake behaviors, cognition, and other primary nervous [...] Read more.
The therapeutic potential of targeting adenosine A2A receptors (A2ARs) is immense due to their broad expression in the body and central nervous system. The role of A2ARs in cardiovascular function, inflammation, sleep/wake behaviors, cognition, and other primary nervous system functions has been extensively studied. Numerous A2AR agonist and antagonist molecules are reported, many of which are currently in clinical trials or have already been approved for treatment. Allosteric modulators can selectively elicit a physiologic response only where and when the orthosteric ligand is released, which reduces the risk of an adverse effect resulting from A2AR activation. Thus, these allosteric modulators have a potential therapeutic advantage over classical agonist and antagonist molecules. This review focuses on the recent developments regarding allosteric A2AR modulation, which is a promising area for future pharmaceutical research because the list of existing allosteric A2AR modulators and their physiologic effects is still short. Full article
(This article belongs to the Special Issue Molecular Circuits Regulating Sleep and Wakeful Consciousness)
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