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Neurobiology of Sleep–Wake Control

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Sleep and its Disorders

Part of the book series: Translational Medicine Research ((TRAMERE))

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Abstract

The chapter provides an introduction to the mechanism underlying the generation and regulation of sleep under physiologic conditions. Sleep–wake behavior is gated by circadian rhythm and paced by the ultradian rhythm called the basic rest–activity cycle (BRAC). Within the framework of these two rhythms, three distinct behavioral states—wakefulness, non-rapid eye movement (NREM) sleep, and REM sleep—are generated by neuronal groups that differ based on their neurotransmitter phenotypes, anatomic locations, and relationship of their activity to the phases of the sleep–wake cycle. Gamma-aminobutyric acid (GABA) plays a major role in this network, with different groups of GABAergic cells contributing to the generation of each of the three behavioral states. Different groups of cholinergic cells support wakefulness or REM sleep. Norepinephrine-, serotonin-, histamine-, and orexin-containing neurons subserve different aspects of wakefulness. The entire network possesses multiple mechanisms that support the homeostatic regulation of sleep. These include the use-dependent control of neurotransmitter synthesis, neurotransmitter receptor trafficking, cellular effects of metabolites (e.g., adenosine), response to depletion of energy stores (e.g., glycogen), as well as actions of sleep-promoting cytokines and growth factors responsive to inflammation and external environment (e.g., synaptic plasticity supporting memory).

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References

  • Alam MA, Kumar S, McGinty D, Alam MN, Szymusiak R. Neuronal activity in the preoptic hypothalamus during sleep deprivation and recovery sleep. J Neurophysiol. 2014;111(2):287–99.

    Article  CAS  PubMed  Google Scholar 

  • Albrecht U. Timing to perfection: the biology of central and peripheral circadian clocks. Neuron. 2012;74(2):246–60.

    Article  CAS  PubMed  Google Scholar 

  • Anaclet C, Lin JS, Vetrivelan R, Krenzer M, Vong L, Fuller PM, et al. Identification and characterization of a sleep-active cell group in the rostral medullary brainstem. J Neurosci. 2012;32(50):17970–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anaclet C, Ferrari L, Arrigoni E, Bass CE, Saper CB, Lu J, et al. The GABAergic parafacial zone is a medullary slow wave sleep-promoting center. Nat Neurosci. 2014;17(9):1217–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arrigoni E, Chen MC, Fuller PM. The anatomical, cellular and synaptic basis of motor atonia during rapid eye movement sleep. J Physiol. 2016;594(19):5391–414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aserinsky E, Kleitman N. Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. Science. 1953;118(3062):273–4.

    Article  CAS  PubMed  Google Scholar 

  • Basheer R, Sherin JE, Saper CB, Morgan JI, McCarley RW, Shiromani PJ. Effects of sleep on wake-induced c-fos expression. J Neurosci. 1997;17(24):9746–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bass J, Takahashi JS. Circadian integration of metabolism and energetics. Science. 2010;330(6009):1349–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benington JH, Heller HC. Does the function of REM sleep concern non-REM sleep or waking? Prog Neurobiol. 1994;44(5):433–49.

    Article  CAS  PubMed  Google Scholar 

  • Benington JH, Kodali SK, Heller HC. Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res. 1995;692(1–2):79–85.

    Article  CAS  PubMed  Google Scholar 

  • Bjorness TE, Dale N, Mettlach G, Sonneborn A, Sahin B, Fienberg AA, et al. An adenosine-mediated glial-neuronal circuit for homeostatic sleep. J Neurosci. 2016;36(13):3709–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blanco-Centurion C, Xu M, Murillo-Rodriguez E, Gerashchenko D, Shiromani AM, Salin-Pascual RJ, et al. Adenosine and sleep homeostasis in the Basal forebrain. J Neurosci. 2006;26(31):8092–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boissard R, Gervasoni D, Schmidt MH, Barbagli B, Fort P, Luppi PH. The rat ponto-medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study. Eur J Neurosci. 2002;16(10):1959–73.

    Article  PubMed  Google Scholar 

  • Borbély AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1(3):195–204.

    PubMed  Google Scholar 

  • Boucetta S, Cisse Y, Mainville L, Morales M, Jones BE. Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat. J Neurosci. 2014;34(13):4708–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brooks PL, Peever JH. Glycinergic and GABAA-mediated inhibition of somatic motoneurons does not mediate rapid eye movement sleep motor atonia. J Neurosci. 2008;28(14):3535–45.

    Google Scholar 

  • Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010;363(27):2638–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab. 2005;90(5):3106–14.

    Article  CAS  PubMed  Google Scholar 

  • Chan E, Steenland HW, Liu H, Horner RL. Endogenous excitatory drive modulating respiratory muscle activity across sleep-wake states. Am J Respir Crit Care Med. 2006;174(11):1264–73.

    Article  CAS  PubMed  Google Scholar 

  • Chandler SH, Chase MH, Nakamura Y. Intracellular analysis of synaptic mechanisms controlling trigeminal motoneuron activity during sleep and wakefulness. J Neurophysiol. 1980;44(2):359–71.

    Article  CAS  PubMed  Google Scholar 

  • Chase MH, Morales FR. The atonia and myoclonia of active (REM) sleep. Annu Rev Psychol. 1990;41:557–84.

    Article  CAS  PubMed  Google Scholar 

  • Chase MH, Soja PJ, Morales FR. Evidence that glycine mediates the postsynaptic potentials that inhibit lumbar motoneurons during the atonia of active sleep. J Neurosci. 1989;9(3):743–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999;98(4):437–51.

    Article  CAS  PubMed  Google Scholar 

  • D’Olimpio F, Renzi P. Ultradian rhythms in young and adult mice: further support for the basic rest-activity cycle. Physiol Behav. 1998;64(5):697–701.

    Article  PubMed  Google Scholar 

  • de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95(1):322–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dentico D, Amici R, Baracchi F, Cerri M, Del Sindaco E, Luppi M, et al. c-Fos expression in preoptic nuclei as a marker of sleep rebound in the rat. Eur J Neurosci. 2009;30(4):651–61.

    Article  PubMed  Google Scholar 

  • Dworak M, McCarley RW, Kim T, Kalinchuk AV, Basheer R. Sleep and brain energy levels: ATP changes during sleep. J Neurosci. 2010;30(26):9007–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • el Mansari M, Sakai K, Jouvet M. Unitary characteristics of presumptive cholinergic tegmental neurons during the sleep-waking cycle in freely moving cats. Exp Brain Res. 1989;76(3):519–29.

    Article  PubMed  Google Scholar 

  • Emens JS, Burgess HJ. Effect of light and melatonin and other melatonin receptor agonists on human circadian physiology. Sleep Med Clin. 2015;10(4):435–53.

    Article  PubMed  PubMed Central  Google Scholar 

  • Feldman JL, Mitchell GS, Nattie EE. Breathing: rhythmicity, plasticity, chemosensitivity. Annu Rev Neurosci. 2003;26:239–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fenik VB, Kubin L. Differential localization of carbachol- and bicuculline-sensitive pontine sites for eliciting REM sleep-like effects in anesthetized rats. J Sleep Res. 2009;18(1):99–112.

    Article  PubMed  Google Scholar 

  • Fenik V, Davies RO, Kubin L. Combined antagonism of aminergic excitatory and amino acid inhibitory receptors in the XII nucleus abolishes REM sleep-like depression of hypoglossal motoneuronal activity. Arch Ital Biol. 2004;142(3):237–49.

    CAS  PubMed  Google Scholar 

  • Fenik VB, Davies RO, Kubin L. Noradrenergic, serotonergic and GABAergic antagonists injected together into the XII nucleus abolish the REM sleep-like depression of hypoglossal motoneuronal activity. J Sleep Res. 2005a;14(4):419–29.

    Article  PubMed  Google Scholar 

  • Fenik VB, Davies RO, Kubin L. REM sleep-like atonia of hypoglossal (XII) motoneurons is caused by loss of noradrenergic and serotonergic inputs. Am J Respir Crit Care Med. 2005b;172(10):1322–30.

    Article  PubMed  Google Scholar 

  • Fort P, Bassetti CL, Luppi PH. Alternating vigilance states: new insights regarding neuronal networks and mechanisms. Eur J Neurosci. 2009;29(9):1741–53.

    Article  CAS  PubMed  Google Scholar 

  • Frank MG. Astroglial regulation of sleep homeostasis. Curr Opin Neurobiol. 2013;23(5):812–8.

    Article  CAS  PubMed  Google Scholar 

  • Franken P, Chollet D, Tafti M. The homeostatic regulation of sleep need is under genetic control. J Neurosci. 2001;21(8):2610–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fung SJ, Chase MH. Postsynaptic inhibition of hypoglossal motoneurons produces atonia of the genioglossal muscle during rapid eye movement sleep. Sleep. 2015;38(1):139–46.

    Article  PubMed  PubMed Central  Google Scholar 

  • Glenn LL, Dement WC. Membrane potential, synaptic activity, and excitability of hindlimb motoneurons during wakefulness and sleep. J Neurophysiol. 1981;46(4):839–54.

    Article  CAS  PubMed  Google Scholar 

  • Grace KP, Hughes SW, Horner RL. Identification of the mechanism mediating genioglossus muscle suppression in REM sleep. Am J Respir Crit Care Med. 2013;187(3):311–9.

    Article  PubMed  Google Scholar 

  • Grace KP, Hughes SW, Horner RL. Identification of a pharmacological target for genioglossus reactivation throughout sleep. Sleep. 2014;37(1):41–50.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gvilia I, Xu F, McGinty D, Szymusiak R. Homeostatic regulation of sleep: a role for preoptic area neurons. J Neurosci. 2006;26(37):9426–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gvilia I, Suntsova N, Angara B, McGinty D, Szymusiak R. Maturation of sleep homeostasis in developing rats: a role for preoptic area neurons. Am J Physiol Regul Integr Comp Physiol. 2011;300(4):R885–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halassa MM, Florian C, Fellin T, Munoz JR, Lee SY, Abel T, et al. Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron. 2009;61(2):213–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassani OK, Lee MG, Henny P, Jones BE. Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep-wake cycle. J Neurosci. 2009a;29(38):11828–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassani OK, Lee MG, Jones BE. Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc Natl Acad Sci U S A. 2009b;106(7):2418–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassani OK, Henny P, Lee MG, Jones BE. GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep. Eur J Neurosci. 2010;32(3):448–57.

    Article  PubMed  PubMed Central  Google Scholar 

  • Havekes R, Park AJ, Tudor JC, Luczak VG, Hansen RT, Ferri SL, et al. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1. eLife. 2016;5:e13424.

    Google Scholar 

  • Hendricks JC, Finn SM, Panckeri KA, Chavkin J, Williams JA, Sehgal A, et al. Rest in Drosophila is a sleep-like state. Neuron. 2000;25(1):129–38.

    Article  CAS  PubMed  Google Scholar 

  • Hobson JA, Lydic R, Baghdoyan HA. Evolving concepts of sleep cycle generation: from brain centers to neuronal populations. Behav Brain Sci. 1986;9:371–448.

    Article  Google Scholar 

  • Horne JA. REM sleep—by default? Neurosci Biobehav Rev. 2000;24(8):777–97.

    Article  CAS  PubMed  Google Scholar 

  • Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol. 2015;72(6):707–12.

    Article  PubMed  Google Scholar 

  • Huber R, Ghilardi MF, Massimini M, Tononi G. Local sleep and learning. Nature. 2004;430(6995):78–81.

    Article  CAS  PubMed  Google Scholar 

  • Ikeda M, Ikeda-Sagara M, Okada T, Clement P, Urade Y, Nagai T, et al. Brain oxidation is an initial process in sleep induction. Neuroscience. 2005;130(4):1029–40.

    Article  CAS  PubMed  Google Scholar 

  • Ingiosi AM, Raymond RM Jr, Pavlova MN, Opp MR. Selective contributions of neuronal and astroglial interleukin-1 receptor 1 to the regulation of sleep. Brain Behav Immun. 2015;48:244–57.

    Article  CAS  PubMed  Google Scholar 

  • Inoue S, Honda K, Komoda Y. Sleep as neuronal detoxification and restitution. Behav Brain Res. 1995;69(1–2):91–6.

    Article  CAS  PubMed  Google Scholar 

  • Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013;12(5):443–53.

    Article  PubMed  Google Scholar 

  • John J, Wu MF, Boehmer LN, Siegel JM. Cataplexy-active neurons in the hypothalamus: implications for the role of histamine in sleep and waking behavior. Neuron. 2004;42(4):619–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones BE. Paradoxical sleep and its chemical/structural substrates in the brain. Neuroscience. 1991;40(3):637–56.

    Article  CAS  PubMed  Google Scholar 

  • Jones BE. From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci. 2005;26(11):578–86.

    Article  CAS  PubMed  Google Scholar 

  • Jouvet M. [Research on the neural structures and responsible mechanisms in different phases of physiological sleep]. Arch Ital Biol 1962;100(2):125–206.

    Google Scholar 

  • Kalsbeek A, Yi CX, la Fleur SE, Buijs RM, Fliers E. Suprachiasmatic nucleus and autonomic nervous system influences on awakening from sleep. Int Rev Neurobiol. 2010;93:91–107.

    Article  PubMed  Google Scholar 

  • Kim Y, Laposky AD, Bergmann BM, Turek FW. Repeated sleep restriction in rats leads to homeostatic and allostatic responses during recovery sleep. Proc Natl Acad Sci U S A. 2007;104(25):10697–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleitman N. Biological rhythms and cycles. Physiol Rev. 1949;29(1):1–30.

    Article  CAS  PubMed  Google Scholar 

  • Kleitman N. Sleep and wakefulness. Chicago: University of Chicago Press; 1963.

    Google Scholar 

  • Kleitman N. Basic rest-activity cycle—22 years later. Sleep. 1982;5(4):311–7.

    Article  CAS  PubMed  Google Scholar 

  • Krueger JM. The role of cytokines in sleep regulation. Curr Pharm Des. 2008;14(32):3408–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krueger JM, Tononi G. Local use-dependent sleep; synthesis of the new paradigm. Curr Top Med Chem. 2011;11(19):2490–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krueger JM, Clinton JM, Winters BD, Zielinski MR, Taishi P, Jewett KA, et al. Involvement of cytokines in slow wave sleep. Prog Brain Res. 2011;193:39–47.

    Article  PubMed  PubMed Central  Google Scholar 

  • Krueger JM, Huang YH, Rector DM, Buysse DJ. Sleep: a synchrony of cell activity-driven small network states. Eur J Neurosci. 2013;38(2):2199–209.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kubin L. Carbachol models of REM sleep: recent developments and new directions. Arch Ital Biol. 2001;139(1–2):147–68.

    CAS  PubMed  Google Scholar 

  • Kubin L. Adventures and tribulations in the search for the mechanisms of the atonia of REM sleep. Sleep. 2008;31(11):1473–6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kubin L. Neural control of the upper airway: respiratory and state-dependent mechanisms. Compr Physiol. 2016;6(4):1801–50.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kubin L, Tojima H, Davies RO, Pack AI. Serotonergic excitatory drive to hypoglossal motoneurons in the decerebrate cat. Neurosci Lett. 1992;139(2):243–8.

    Article  CAS  PubMed  Google Scholar 

  • Kubin L, Kimura H, Tojima H, Davies RO, Pack AI. Suppression of hypoglossal motoneurons during the carbachol-induced atonia of REM sleep is not caused by fast synaptic inhibition. Brain Res. 1993;611(2):300–12.

    Article  CAS  PubMed  Google Scholar 

  • Lai YY, Clements JR, Siegel JM. Glutamatergic and cholinergic projections to the pontine inhibitory area identified with horseradish peroxidase retrograde transport and immunohistochemistry. J Comp Neurol. 1993;336(3):321–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai YY, Clements JR, Wu XY, Shalita T, Wu JP, Kuo JS, et al. Brainstem projections to the ventromedial medulla in cat: retrograde transport horseradish peroxidase and immunohistochemical studies. J Comp Neurol. 1999;408(3):419–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Landolt HP. Sleep homeostasis: a role for adenosine in humans? Biochem Pharmacol. 2008;75(11):2070–9.

    Article  CAS  PubMed  Google Scholar 

  • Lavie P. REM periodicity under ultrashort sleep/wake cycle in narcoleptic patients. Can J Psychol. 1991;45(2):185–93.

    Article  CAS  PubMed  Google Scholar 

  • Leger L, Goutagny R, Sapin E, Salvert D, Fort P, Luppi PH. Noradrenergic neurons expressing Fos during waking and paradoxical sleep deprivation in the rat. J Chem Neuroanat. 2009;37(3):149–57.

    Article  CAS  PubMed  Google Scholar 

  • Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999;98(3):365–76.

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Thankachan S, Kaur S, Begum S, Blanco-Centurion C, Sakurai T, et al. Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice. Eur J Neurosci. 2008;28(7):1382–93.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lo CC, Chou T, Penzel T, Scammell TE, Strecker RE, Stanley HE, et al. Common scale-invariant patterns of sleep-wake transitions across mammalian species. Proc Natl Acad Sci U S A. 2004;101(50):17545–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu J, Greco MA, Shiromani P, Saper CB. Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep. J Neurosci. 2000;20(10):3830–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu J, Sherman D, Devor M, Saper CB. A putative flip-flop switch for control of REM sleep. Nature. 2006;441(7093):589–94.

    Article  CAS  PubMed  Google Scholar 

  • Luppi PH, Clement O, Sapin E, Peyron C, Gervasoni D, Leger L, et al. Brainstem mechanisms of paradoxical (REM) sleep generation. Pflugers Arch. 2012;463(1):43–52.

    Article  CAS  PubMed  Google Scholar 

  • Luppi PH, Peyron C, Fort P. Not a single but multiple populations of GABAergic neurons control sleep. Sleep Med Rev. 2017;32:85–94.

    Article  PubMed  Google Scholar 

  • Lydic R, Baghdoyan HA. Sleep, anesthesiology, and the neurobiology of arousal state control. Anesthesiology. 2005;103(6):1268–95.

    Article  PubMed  Google Scholar 

  • Mackiewicz M, Nikonova EV, Zimmerman JE, Galante RJ, Zhang L, Cater JR, et al. Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation. J Neurochem. 2003;85(2):348–57.

    Article  CAS  PubMed  Google Scholar 

  • Maloney KJ, Mainville L, Jones BE. c-Fos expression in GABAergic, serotonergic, and other neurons of the pontomedullary reticular formation and raphe after paradoxical sleep deprivation and recovery. J Neurosci. 2000;20(12):4669–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuki T, Takasu M, Hirose Y, Murakoshi N, Sinton CM, Motoike T, et al. GABAA receptor-mediated input change on orexin neurons following sleep deprivation in mice. Neuroscience. 2015;284:217–24.

    Google Scholar 

  • McCarley RW, Hobson JA. Neuronal excitability modulation over the sleep cycle: a structural and mathematical model. Science. 1975;189(4196):58–60.

    Article  CAS  PubMed  Google Scholar 

  • McPartland RJ, Kupfer DJ. Rapid eye movement sleep cycle, clock time and sleep onset. Electroencephalogr Clin Neurophysiol. 1978;45(2):178–85.

    Article  CAS  PubMed  Google Scholar 

  • Mignot E, Taheri S, Nishino S. Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders. Nat Neurosci. 2002;5(Suppl):1071–5.

    Article  CAS  PubMed  Google Scholar 

  • Mistlberger RE. Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus. Brain Res Brain Res Rev. 2005;49(3):429–54.

    Article  PubMed  Google Scholar 

  • Modirrousta M, Mainville L, Jones BE. Orexin and MCH neurons express c-Fos differently after sleep deprivation vs. recovery and bear different adrenergic receptors. Eur J Neurosci. 2005;21(10):2807–16.

    Article  PubMed  Google Scholar 

  • Modirrousta M, Mainville L, Jones BE. Dynamic changes in GABAA receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery. BMC Neurosci. 2007;8:15.

    Google Scholar 

  • Morales FR, Chase MH. Repetitive synaptic potentials responsible for inhibition of spinal cord motoneurons during active sleep. Exp Neurol. 1982;78(2):471–6.

    Article  CAS  PubMed  Google Scholar 

  • Morales FR, Boxer P, Chase MH. Behavioral state-specific inhibitory postsynaptic potentials impinge on cat lumbar motoneurons during active sleep. Exp Neurol. 1987;98(2):418–35.

    Article  CAS  PubMed  Google Scholar 

  • Morrison JL, Sood S, Liu H, Park E, Liu X, Nolan P, et al. Role of inhibitory amino acids in control of hypoglossal motor outflow to genioglossus muscle in naturally sleeping rats. J Physiol. 2003;552(Pt 3):975–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nadjar A, Blutstein T, Aubert A, Laye S, Haydon PG. Astrocyte-derived adenosine modulates increased sleep pressure during inflammatory response. Glia. 2013;61(5):724–31.

    Article  PubMed  Google Scholar 

  • Naidoo N, Ferber M, Galante RJ, McShane B, Hu JH, Zimmerman J, et al. Role of Homer proteins in the maintenance of sleep-wake states. PLoS One. 2012;7(4):e35174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson SB, Sjostrom PJ, Turrigiano GG. Rate and timing in cortical synaptic plasticity. Philos Trans R Soc Lond Ser B Biol Sci. 2002;357(1428):1851–7.

    Article  Google Scholar 

  • Nelson SE, Duricka DL, Campbell K, Churchill L, Krueger JM. Homer1a and 1bc levels in the rat somatosensory cortex vary with the time of day and sleep loss. Neurosci Lett. 2004;367(1):105–8.

    Article  CAS  PubMed  Google Scholar 

  • Nykamp K, Rosenthal L, Folkerts M, Roehrs T, Guido P, Roth T. The effects of REM sleep deprivation on the level of sleepiness/alertness. Sleep. 1998;21(6):609–14.

    Article  CAS  PubMed  Google Scholar 

  • Obal F Jr, Krueger JM. GHRH and sleep. Sleep Med Rev. 2004;8(5):367–77.

    Article  PubMed  Google Scholar 

  • Obal F Jr, Fang J, Payne LC, Krueger JM. Growth-hormone-releasing hormone mediates the sleep-promoting activity of interleukin-1 in rats. Neuroendocrinology. 1995;61(5):559–65.

    Article  CAS  PubMed  Google Scholar 

  • Ocampo-Garces A, Vivaldi EA. Short-term homeostasis of REM sleep assessed in an intermittent REM sleep deprivation protocol in the rat. J Sleep Res. 2002;11(1):81–9.

    Article  PubMed  Google Scholar 

  • Opp MR, Krueger JM. Sleep and immunity: a growing field with clinical impact. Brain Behav Immun. 2015;47:1–3.

    Article  PubMed  PubMed Central  Google Scholar 

  • Orem J. Neuronal mechanisms of respiration in REM sleep. Sleep. 1980;3(3–4):251–67.

    Article  CAS  PubMed  Google Scholar 

  • Orem J, Kubin L. Respiratory physiology: central neural control. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 4th ed. Philadelphia, PA: Elsevier-Saunders; 2005. p. 213–23.

    Chapter  Google Scholar 

  • Paul KN, Losee-Olson S, Pinckney L, Turek FW. The ability of stress to alter sleep in mice is sensitive to reproductive hormones. Brain Res. 2009;1305:74–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pedroarena C, Castillo P, Chase MH, Morales FR. The control of jaw-opener motoneurons during active sleep. Brain Res. 1994;653(1–2):31–8.

    Article  CAS  PubMed  Google Scholar 

  • Petit JM, Burlet-Godinot S, Magistretti PJ, Allaman I. Glycogen metabolism and the homeostatic regulation of sleep. Metab Brain Dis. 2015;30(1):263–79.

    Article  CAS  PubMed  Google Scholar 

  • Peyron C, Sapin E, Leger L, Luppi PH, Fort P. Role of the melanin-concentrating hormone neuropeptide in sleep regulation. Peptides. 2009;30(11):2052–9.

    Article  CAS  PubMed  Google Scholar 

  • Pollock MS, Mistlberger RE. Rapid eye movement sleep induction by microinjection of the GABA-A antagonist bicuculline into the dorsal subcoeruleus area of the rat. Brain Res. 2003;962(1–2):68–77.

    Article  CAS  PubMed  Google Scholar 

  • Porkka-Heiskanen T, Strecker RE, McCarley RW. Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience. 2000;99(3):507–17.

    Article  CAS  PubMed  Google Scholar 

  • Postuma RB, Gagnon JF, Vendette M, Montplaisir JY. Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson’s disease. Brain. 2009;132(Pt 12):3298–307.

    Article  CAS  PubMed  Google Scholar 

  • Qiu MH, Chen MC, Lu J. Cortical neuronal activity does not regulate sleep homeostasis. Neuroscience. 2015;297:211–8.

    Article  CAS  PubMed  Google Scholar 

  • Radulovacki M. Role of adenosine in sleep in rats. Rev Clin Basic Pharm. 1985;5(3–4):327–39.

    CAS  PubMed  Google Scholar 

  • Rai S, Kumar S, Alam MA, Szymusiak R, McGinty D, Alam MN. A1 receptor mediated adenosinergic regulation of perifornical-lateral hypothalamic area neurons in freely behaving rats. Neuroscience. 2010;167(1):40–8.

    Article  CAS  PubMed  Google Scholar 

  • Rector DM, Schei JL, Van Dongen HP, Belenky G, Krueger JM. Physiological markers of local sleep. Eur J Neurosci. 2009;29(9):1771–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Reid KJ, Abbott SM. Jet lag and shift work disorder. Sleep Med Clin. 2015;10(4):523–35.

    Article  PubMed  Google Scholar 

  • Reiner PB. Are mesopontine cholinergic neurons either necessary or sufficient components of the ascending reticular activating system? Semin Neurosci. 1995;7(5):355–9.

    Article  Google Scholar 

  • Richter DW, Spyer KM. Studying rhythmogenesis of breathing: comparison of in vivo and in vitro models. Trends Neurosci. 2001;24(8):464–72.

    Article  CAS  PubMed  Google Scholar 

  • Rolls A, Pang WW, Ibarra I, Colas D, Bonnavion P, Korin B, et al. Sleep disruption impairs haematopoietic stem cell transplantation in mice. Nat Commun. 2015;6:8516.

    Article  CAS  PubMed  Google Scholar 

  • Rukhadze I, Kubin L. Mesopontine cholinergic projections to the hypoglossal motor nucleus. Neurosci Lett. 2007;413(2):121–5.

    Article  CAS  PubMed  Google Scholar 

  • Sanford LD, Tang X, Xiao J, Ross RJ, Morrison AR. GABAergic regulation of REM sleep in reticularis pontis oralis and caudalis in rats. J Neurophysiol. 2003;90(2):938–45.

    Article  CAS  PubMed  Google Scholar 

  • Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci. 2001;24(12):726–31.

    Article  CAS  PubMed  Google Scholar 

  • Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010;68(6):1023–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sherin JE, Shiromani PJ, McCarley RW, Saper CB. Activation of ventrolateral preoptic neurons during sleep. Science. 1996;271(5246):216–9.

    Article  CAS  PubMed  Google Scholar 

  • Shouse MN, Siegel JM. Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep. Brain Res. 1992;571(1):50–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegel JM. The neurobiology of sleep. Semin Neurol. 2009;29(4):277–96.

    Article  PubMed  PubMed Central  Google Scholar 

  • Silver R, Lesauter J. Circadian and homeostatic factors in arousal. Ann N Y Acad Sci. 2008;1129:263–74.

    Article  PubMed  Google Scholar 

  • Soja PJ, Finch DM, Chase MH. Effect of inhibitory amino acid antagonists on masseteric reflex suppression during active sleep. Exp Neurol. 1987;96(1):178–93.

    Article  CAS  PubMed  Google Scholar 

  • Steriade M, Datta S, Pare D, Oakson G, Curro Dossi RC. Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems. J Neurosci. 1990;10(8):2541–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sukhotinsky I, Zalkind V, Lu J, Hopkins DA, Saper CB, Devor M. Neural pathways associated with loss of consciousness caused by intracerebral microinjection of GABA A-active anesthetics. Eur J Neurosci. 2007;25(5):1417–36.

    Article  CAS  PubMed  Google Scholar 

  • Thakkar MM, Winston S, McCarley RW. A1 receptor and adenosinergic homeostatic regulation of sleep-wakefulness: effects of antisense to the A1 receptor in the cholinergic basal forebrain. J Neurosci. 2003;23(10):4278–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thankachan S, Kaur S, Shiromani PJ. Activity of pontine neurons during sleep and cataplexy in hypocretin knock-out mice. J Neurosci. 2009;29(5):1580–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tong X, Yin L. Circadian rhythms in liver physiology and liver diseases. Compr Physiol. 2013;3(2):917–40.

    Article  PubMed  Google Scholar 

  • Turrigiano GG. The self-tuning neuron: synaptic scaling of excitatory synapses. Cell. 2008;135(3):422–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uguccioni G, Golmard JL, de Fontreaux AN, Leu-Semenescu S, Brion A, Arnulf I. Fight or flight? Dream content during sleepwalking/sleep terrors vs. rapid eye movement sleep behavior disorder. Sleep Med. 2013;14(5):391–8.

    Article  PubMed  Google Scholar 

  • Uschakov A, Gong H, McGinty D, Szymusiak R. Efferent projections from the median preoptic nucleus to sleep- and arousal-regulatory nuclei in the rat brain. Neuroscience. 2007;150(1):104–20.

    Article  CAS  PubMed  Google Scholar 

  • Uschakov A, Grivel J, Cvetkovic-Lopes V, Bayer L, Bernheim L, Jones BE, et al. Sleep-deprivation regulates alpha-2 adrenergic responses of rat hypocretin/orexin neurons. PLoS One. 2011;6(2):e16672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vanini G, Nemanis K, Baghdoyan HA, Lydic R. GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation. Eur J Neurosci. 2014;40(1):2264–73.

    Article  PubMed  PubMed Central  Google Scholar 

  • Veasey SC, Panckeri KA, Hoffman EA, Pack AI, Hendricks JC. The effects of serotonin antagonists in an animal model of sleep-disordered breathing. Am J Respir Crit Care Med. 1996;153(2):776–86.

    Article  CAS  PubMed  Google Scholar 

  • Volgin DV, Kubin L. Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in vitro. Biochem Biophys Res Commun. 2007;353(3):726–32.

    Google Scholar 

  • Volgin DV, Lu JW, Stettner GM, Mann GL, Ross RJ, Morrison AR, et al. Time- and behavioral state-dependent changes in posterior hypothalamic GABAA receptors contribute to the regulation of sleep. PLoS One. 2014;9(1):e86545.

    Google Scholar 

  • von Economo C. Sleep as a problem of localization. J Nerv Ment Dis. 1930;71:249–59.

    Article  Google Scholar 

  • Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, et al. Cortical firing and sleep homeostasis. Neuron. 2009;63(6):865–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vyazovskiy VV, Cirelli C, Tononi G. Electrophysiological correlates of sleep homeostasis in freely behaving rats. Prog Brain Res. 2011;193:17–38.

    Article  PubMed  PubMed Central  Google Scholar 

  • Weber F, Chung S, Beier KT, Xu M, Luo L, Dan Y. Control of REM sleep by ventral medulla GABAergic neurons. Nature. 2015;526(7573):435–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weng FJ, Williams RH, Hawryluk JM, Lu J, Scammell TE, Saper CB, et al. Carbachol excites sublaterodorsal nucleus neurons projecting to the spinal cord. J Physiol. 2014;592(7):1601–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White DP, Younes MK. Obstructive sleep apnea. Compr Physiol. 2012;2(4):2541–94.

    Article  PubMed  Google Scholar 

  • Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY, et al. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron. 2003;38(5):715–30.

    Article  CAS  PubMed  Google Scholar 

  • Wu MF, Gulyani SA, Yau E, Mignot E, Phan B, Siegel JM. Locus coeruleus neurons: cessation of activity during cataplexy. Neuroscience. 1999;91(4):1389–99.

    Article  CAS  PubMed  Google Scholar 

  • Wu MF, John J, Boehmer LN, Yau D, Nguyen GB, Siegel JM. Activity of dorsal raphe cells across the sleep-waking cycle and during cataplexy in narcoleptic dogs. J Physiol. 2004;554(Pt 1):202–15.

    Article  CAS  PubMed  Google Scholar 

  • Xi MC, Morales FR, Chase MH. Evidence that wakefulness and REM sleep are controlled by a GABAergic pontine mechanism. J Neurophysiol. 1999;82(4):2015–9.

    Article  CAS  PubMed  Google Scholar 

  • Xu M, Chung S, Zhang S, Zhong P, Ma C, Chang WC, et al. Basal forebrain circuit for sleep-wake control. Nat Neurosci. 2015;18(11):1641–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamuy J, Fung SJ, Xi M, Morales FR, Chase MH. Hypoglossal motoneurons are postsynaptically inhibited during carbachol-induced rapid eye movement sleep. Neuroscience. 1999;94(1):11–5.

    Article  CAS  PubMed  Google Scholar 

  • Yanik G, Radulovacki M. REM sleep deprivation up-regulates adenosine A1 receptors. Brain Res. 1987;402(2):362–4.

    Article  CAS  PubMed  Google Scholar 

  • Zecharia AY, Nelson LE, Gent TC, Schumacher M, Jurd R, Rudolph U, et al. The involvement of hypothalamic sleep pathways in general anesthesia: testing the hypothesis using the GABAA receptor beta3N265M knock-in mouse. J Neurosci. 2009;29(7):2177–87.

    Google Scholar 

  • Zhang S, Lin L, Kaur S, Thankachan S, Blanco-Centurion C, Yanagisawa M, et al. The development of hypocretin (orexin) deficiency in hypocretin/ataxin-3 transgenic rats. Neuroscience. 2007;148(1):34–43.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Our research discussed in this review has been supported by the following grants from the National Institutes of Health (USA): HL042236, HL047600, HL060287, HL071097, and HL074385.

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  1. Department of Biomedical Sciences 209E/VET, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Leszek Kubin

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  1. John Miclot Professor, Division of Sleep Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Allan I. Pack

  2. Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Qing Yun Li

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Kubin, L. (2022). Neurobiology of Sleep–Wake Control. In: Pack, A.I., Li, Q.Y. (eds) Sleep and its Disorders. Translational Medicine Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-2168-2_2

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