Review

Authors: Sebastian C Holst, Hans-Peter Landolt

The regulated alternations between wakefulness and sleep states reflect complex behavioral processes, orchestrated by distinct neurochemical changes in brain parenchyma. No single neurotransmitter or neuromodulator controls the sleep-wake states in isolation. Rather, fine-tuned interactions within organized neuronal circuits regulate waking and sleep states and drive their transitions. Structural or functional dysregulation and medications interfering with these ensembles can lead to sleep-wake disorders and exert wanted or unwanted pharmacological actions on sleep-wake states. Knowledge of the neurochemical bases of sleep-wake states, which will be discussed in this article, provides the conceptual framework for understanding pharmacological effects on sleep and wake.

Topics: Animals; Brain Chemistry; Humans; Neurotransmitter Agents; Sleep; Sleep Wake Disorders; Wakefulness

PubMed: 29759265
DOI: 10.1016/j.jsmc.2018.03.002

Review

Authors: William J Schwartz, Elizabeth B Klerman

Endogenous central and peripheral circadian oscillators are key to organizing multiple aspects of mammalian physiology; this clock tracks the day-night cycle and governs behavioral and physiologic rhythmicity. Flexibility in the timing and duration of sleep and wakefulness, critical to the survival of species, is the result of a complex, dynamic interaction between 2 regulatory processes: the clock and a homeostatic drive that increases with wake duration and decreases during sleep. When circadian rhythmicity and sleep homeostasis are misaligned-as in shifted schedules, time zone transitions, aging, or disease-sleep, metabolic, and other disorders may ensue.

Topics: Animals; Circadian Rhythm; Homeostasis; Humans; Sleep; Wakefulness

PubMed: 31256784
DOI: 10.1016/j.ncl.2019.03.001

Review

Authors: Zachary Zamore, Sigrid C Veasey

Recent studies in both humans and animal models call into question the completeness of recovery after chronic sleep disruption. Studies in humans have identified cognitive domains particularly vulnerable to delayed or incomplete recovery after chronic sleep disruption, including sustained vigilance and episodic memory. These findings, in turn, provide a focus for animal model studies to critically test the lasting impact of sleep loss on the brain. Here, we summarize the human response to sleep disruption and then discuss recent findings in animal models examining recovery responses in circuits pertinent to vigilance and memory. We then propose pathways of injury common to various forms of sleep disruption and consider the implications of this injury in aging and in neurodegenerative disorders.

Topics: Aging; Animals; Brain; Humans; Memory, Episodic; Sleep; Wakefulness

PubMed: 35691776
DOI: 10.1016/j.tins.2022.05.007

Review

Authors: Mandeep Rana, Claudia Riffo Allende, Tomás Mesa Latorre...

Sleep is an active and cyclic physiological process that has a critical impact on health. Its functions are numerous: growth, development, learning, memory, synaptic efficiency, regulation of behavior, emotion, immune strengthening and cleaning time of neurotoxic substances. During the first years of life, there are a number of important changes in development, which lead to the expected pattern of sleep and wakefulness in adults. The sleep occupies a third of the adult's life. However, sleeping during the first months of life takes up more than 50% of time. This review of the topic will describe normal sleep patterns in childhood.

Topics: Child; Humans; Sleep; Wakefulness

PubMed: 31603839
DOI: No ID Found

Authors: Amir Segev, Francisco Garcia-Oscos, Saïd Kourrich...

Whole-cell patch-clamp recording is an electrophysiological technique that allows the study of the electrical properties of a substantial part of the neuron. In this configuration, the micropipette is in tight contact with the cell membrane, which prevents current leakage and thereby provides more accurate ionic current measurements than the previously used intracellular sharp electrode recording method. Classically, whole-cell recording can be performed on neurons in various types of preparations, including cell culture models, dissociated neurons, neurons in brain slices, and in intact anesthetized or awake animals. In summary, this technique has immensely contributed to the understanding of passive and active biophysical properties of excitable cells. A major advantage of this technique is that it provides information on how specific manipulations (e.g., pharmacological, experimenter-induced plasticity) may alter specific neuronal functions or channels in real-time. Additionally, significant opening of the plasma membrane allows the internal pipette solution to freely diffuse into the cytoplasm, providing means for introducing drugs, e.g., agonists or antagonists of specific intracellular proteins, and manipulating these targets without altering their functions in neighboring cells. This article will focus on whole-cell recording performed on neurons in brain slices, a preparation that has the advantage of recording neurons in relatively well preserved brain circuits, i.e., in a physiologically relevant context. In particular, when combined with appropriate pharmacology, this technique is a powerful tool allowing identification of specific neuroadaptations that occurred following any type of experiences, such as learning, exposure to drugs of abuse, and stress. In summary, whole-cell patch-clamp recordings in brain slices provide means to measure in ex vivo preparation long-lasting changes in neuronal functions that have developed in intact awake animals.

Topics: Animals; Brain; Mice; Neural Pathways; Neurons; Patch-Clamp Techniques; Wakefulness

PubMed: 27341060
DOI: 10.3791/54024

Authors: Georgia Trakada

Various hormones and neuropeptides implicated in energy metabolism also regulate sleep cycles and wakefulness and promote adequate and restorative sleep [...].

Topics: Sleep; Neuropeptides; Eating; Energy Intake; Diet; Wakefulness

PubMed: 37242158
DOI: 10.3390/nu15102276

Authors: Roberto De Luca, Stefano Nardone, Kevin P Grace...

Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.

Topics: Animals; Arousal; Humans; Neurons; Orexins; Sleep; Wakefulness

PubMed: 35851580
DOI: 10.1038/s41467-022-31591-y

Review

Authors: Clifford B Saper, Patrick M Fuller

Although earlier models of brain circuitry controlling wake-sleep focused on monaminergic and cholinergic arousal systems, recent evidence indicates that these play mainly a modulatory role, and that the backbone of the wake-sleep regulatory system depends upon fast neurotransmitters, such as glutmate and GABA. We review here recent advances in understanding the role these systems play in controlling sleep and wakefulness.

Topics: Brain; Humans; Sleep; Wakefulness

PubMed: 28577468
DOI: 10.1016/j.conb.2017.03.021

Authors: Mengyao Li, Wen Li, Shanshan Liang...

The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria terminalis (BNST) play a critical role in stress and fear that relied on heightened arousal. Nevertheless, it remains unclear whether BNST GABAergic neurons are involved in the regulation of sleep-wakefulness and anesthesia. Here, using in vivo fiber photometry combined with electroencephalography, electromyography, and video recordings, we found that BNST GABAergic neurons exhibited arousal-state-dependent alterations, with high activities in both wakefulness and rapid-eye movement sleep, but suppressed during anesthesia. Optogenetic activation of these neurons could initiate and maintain wakefulness, and even induce arousal from anesthesia. However, chronic lesion of BNST GABAergic neurons altered spontaneous sleep-wakefulness architecture during the dark phase, but not induction and emergence from anesthesia. Furthermore, we also discovered that the BNST-ventral tegmental area pathway might participate in promoting wakefulness and reanimation from steady-state anesthesia. Collectively, our study explores new elements in neural circuit mechanisms underlying sleep-wakefulness and anesthesia, which may contribute to a more comprehensive understanding of consciousness and the development of innovative anesthetics.

Topics: Wakefulness; Septal Nuclei; Sleep; GABAergic Neurons; Anesthesia, General

PubMed: 38503808
DOI: 10.1038/s42003-024-06028-5

Authors: Alessandro Viganò, Majid Ghareghani, Birendra Mallick...

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