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      Neural Substrates for the Regulation of Sleep and General Anesthesia

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          Abstract

          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.

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          Molecular, spatial and functional single-cell profiling of the hypothalamic preoptic region

          Jeffrey R. Moffitt, Dhananjay Bambah-Mukku, Stephen Eichhorn … (2018)
          The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei, including the molecular identity, spatial organization, and function of distinct cell types, is poorly understood. Here, we developed an imaging-based in situ cell type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.
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            Neural substrates of awakening probed with optogenetic control of hypocretin neurons.

            Antoine Adamantidis, Feng Zhang, Alexander M Aravanis … (2007)
            The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.
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              General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal.

              Nicholas Franks (2008)
              The mechanisms through which general anaesthetics, an extremely diverse group of drugs, cause reversible loss of consciousness have been a long-standing mystery. Gradually, a relatively small number of important molecular targets have emerged, and how these drugs act at the molecular level is becoming clearer. Finding the link between these molecular studies and anaesthetic-induced loss of consciousness presents an enormous challenge, but comparisons with the features of natural sleep are helping us to understand how these drugs work and the neuronal pathways that they affect. Recent work suggests that the thalamus and the neuronal networks that regulate its activity are the key to understanding how anaesthetics cause loss of consciousness.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Curr Neuropharmacol
                Journal ID (iso-abbrev): Curr Neuropharmacol
                Journal ID (publisher-id): CN
                Title: Current Neuropharmacology
                Publisher: Bentham Science Publishers
                ISSN (Print): 1570-159X
                ISSN (Electronic): 1875-6190
                Publication date (Electronic): 10 January 2022
                Publication date (Print): 10 January 2022
                Volume: 20
                Issue: 1
                Pages: 72-84
                Affiliations
                [1 ]Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University , Xi’an, , China
                Author notes
                [* ]Address correspondence to this author at the Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China; E-mail: hldong6@ 123456hotmail.com
                Article
                Publisher ID: CN-20-72
                DOI: 10.2174/1570159X19666211214144639
                PMC ID: 9199549
                PubMed ID: 34906058
                SO-VID: ab691e76-b0b2-465e-8d1a-212227e8d6cd
                Copyright © © 2022 Bentham Science Publishers
                License:

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                Date received : 18 August 2021
                Date revision received : 09 November 2021
                Date accepted : 10 December 2021
                Categories
                Subject: Neurology

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: sleep,anesthesia,neural circuits,wakefulness,unconsciousness,sleep-arousal regulatory nuclei
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: sleep, anesthesia, neural circuits, wakefulness, unconsciousness, sleep-arousal regulatory nuclei

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