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Autonomic regulation during sleep and wakefulness: a review with implications for defining the pathophysiology of neurological disorders

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Abstract

Cardiovascular and respiratory parameters change during sleep and wakefulness. This observation underscores an important, albeit incompletely understood, role for the central nervous system in the differential regulation of autonomic functions. Understanding sleep/wake-dependent sympathetic modulations provides insights into diseases involving autonomic dysfunction. The purpose of this review was to define the central nervous system nuclei regulating sleep and cardiovascular function and to identify reciprocal networks that may underlie autonomic symptoms of disorders such as insomnia, sleep apnea, restless leg syndrome, rapid eye movement sleep behavior disorder, and narcolepsy/cataplexy. In this review, we examine the functional and anatomical significance of hypothalamic, pontine, and medullary networks on sleep, cardiovascular function, and breathing.

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Abbreviations

ANS:

Autonomic nervous system

BP:

Blood pressure

CNS:

Central nervous system

CV:

Cardiovascular

EEG:

Electroencephalogram

EMG:

Electromyogram

FFI:

Fatal familial insomnia

GABA:

Gamma-aminobutyric acid

NTS:

Nucleus of the solitary tract

OSA:

Obstructive sleep apnea

PAG:

Periaqueductal grey

POTS:

Postural orthostatic tachycardia syndrome

PPT:

Pedunculopontine tegmentum

REM:

Rapid eye movement

RLS:

Restless leg syndrome

RVLM:

Rostral ventrolateral medulla

SRAH:

Sleep-related alveolar hypoventilation

UARS:

Upper airway resistance syndrome

VLPO:

Ventrolateral preoptic nucleus

References

  1. Descartes R, Cress D (1993) Meditations on first philosophy. Hackett, Indianapolis

    Google Scholar 

  2. Locke J, Nidditch P (1975) An essay concerning human understanding. Clarendon Press, Oxford

    Google Scholar 

  3. Aserinsky E, Kleitman N (1953) Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. Science 118:273–274

    Article  CAS  Google Scholar 

  4. Chen WW, Xiong XQ, Chen Q, Li YH, Kang YM, Zhu GQ (2015) Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension. Acta Physiol (Oxf) 213:778–794

    Article  CAS  Google Scholar 

  5. Andresen MC, Doyle MW, Jin YH, Bailey TW (2001) Cellular mechanisms of baroreceptor integration at the nucleus tractus solitarius. Ann New York Acad Sci 940:132–141

    Article  CAS  Google Scholar 

  6. Michelini LC (2007) The NTS and integration of cardiovascular control during exercise in normotensive and hypertensive individuals. Curr Hypertens Rep 9:214–221

    Article  Google Scholar 

  7. Zoccal DB, Furuya WI, Bassi M, Colombari DSA, Colombari E (2014) The nucleus of the solitary tract and the coordination of respiratory and sympathetic activities. Front Physiol 5:238. https://doi.org/10.3389/fphys.2014.00238

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nishi EE, Bergamaschi CT, Campos RR (2015) The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation. Exp Physiol 100:479–484

    Article  Google Scholar 

  9. DiBona GF, Kopp UC (1997) Neural control of renal function. Physiol Rev 77:75–197

    Article  CAS  Google Scholar 

  10. Baekey DM, Molkov YI, Paton JF, Rybak IA, Dick TE (2010) Effect of baroreceptor stimulation on the respiratory pattern: insights into respiratory–sympathetic interactions. Respir Physiol Neurobiol 174:135–145

    Article  Google Scholar 

  11. Spyer KM, Gourine AV (2009) Chemosensory pathways in the brainstem controlling cardiorespiratory activity. Philos Trans R Soc Lond B Biol Sci 364:2603–2610

    Article  Google Scholar 

  12. Saper CB, Fuller PM (2017) Wake–sleep circuitry: an overview. Curr Opin Neurobiol 44:186–192

    Article  CAS  Google Scholar 

  13. Harris CD (2005) Neurophysiology of sleep and wakefulness. Respir Care Clin N Am 11:567–586

    PubMed  Google Scholar 

  14. Gvilia I (2010) Underlying brain mechanisms that regulate sleep–wakefulness cycles. Int Rev Neurobiol 93:1–21

    Article  Google Scholar 

  15. Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE (2010) Sleep state switching. Neuron 68:1023–1042

    Article  CAS  Google Scholar 

  16. de Zambotti M, Trinder J, Silvani A, Colrain IM, Baker FC (2018) Dynamic coupling between the central and autonomic nervous systems during sleep: a review. Neurosci Biobehav Rev 90:84–103

    Article  Google Scholar 

  17. Krukoff TL, Harris KH, Jhamandas JH (1993) Efferent projections from the parabrachial nucleus demonstrated with the anterograde tracer Phaseolus vulgaris leucoagglutinin. Brain Res Bull 30:163–172

    Article  CAS  Google Scholar 

  18. Felder RB, Mifflin SW (1988) Modulation of carotid sinus afferent input to nucleus tractus solitarius by parabrachial nucleus stimulation. Circ Res 63:35–49

    Article  CAS  Google Scholar 

  19. Hayward LF (2007) Midbrain modulation of the cardiac baroreflex involves excitation of lateral parabrachial neurons in the rat. Brain Res 1145:117–127

    Article  CAS  Google Scholar 

  20. Jafari B (2017) Sleep architecture and blood pressure. Sleep Med Clin 12:161–166

    Article  Google Scholar 

  21. Silvani A, Dampney RA (2013) Central control of cardiovascular function during sleep. Am J Physiol Heart Circ Physiol 305:H1683–H1692

    Article  CAS  Google Scholar 

  22. Sowho M, Amatoury J, Kirkness JP, Patil SP (2014) Sleep and respiratory physiology in adults. Clin Chest Med 35:469–481

    Article  Google Scholar 

  23. Donlea JM, Alam MN, Szymusiak R (2017) Neuronal substrates of sleep homeostasis; lessons from flies, rats and mice. Curr Opin Neurobiol 44:228–235

    Article  CAS  Google Scholar 

  24. Uschakov A, Gong H, McGinty D, Szymusiak R (2006) Sleep-active neurons in the preoptic area project to the hypothalamic paraventricular nucleus and perifornical lateral hypothalamus. Eur J Neurosci 23:3284–3296

    Article  Google Scholar 

  25. Uschakov A, Gong H, McGinty D, Szymusiak R (2007) Efferent projections from the median preoptic nucleus to sleep- and arousal-regulatory nuclei in the rat brain. Neuroscience 150:104–120

    Article  CAS  Google Scholar 

  26. Lozić M, Šarenac O, Murphy D, Japundžić-Žigon N (2018) Vasopressin, central autonomic control and blood pressure regulation. Curr Hypertens Rep 20:11

    Article  Google Scholar 

  27. Siclari F, Tononi G (2017) Local aspects of sleep and wakefulness. Curr Opin Neurobiol 44:222–227

    Article  CAS  Google Scholar 

  28. Schwartz JRL, Roth T (2008) Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol 6:367–378

    Article  CAS  Google Scholar 

  29. Saper CB (2013) The neurobiology of sleep. Continuum (Minneap Minn) 19:19–31

    Google Scholar 

  30. Suntsova N, Szymusiak R, Alam MN, Guzman-Marin R, McGinty D (2002) Sleep–waking discharge patterns of median preoptic nucleus neurons in rats. J Physiol 543:665–677

    Article  CAS  Google Scholar 

  31. Van Dort CJ, Zachs DP, Kenny JD, Zheng S, Goldblum RR, Gelwan NA, Ramos DM, Nolan MA, Wang K, Weng FJ, Lin Y, Wilson MA, Brown EN (2015) Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep. Proc Natl Acad Sci USA 112:584–589

    Article  Google Scholar 

  32. Saper CB, Scammell TE, Lu J (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature 437:1257–1263

    Article  CAS  Google Scholar 

  33. Monti JM (2010) The structure of the dorsal raphe nucleus and its relevance to the regulation of sleep and wakefulness. Sleep Med Rev 14:307–317

    Article  Google Scholar 

  34. Gould GA, Gugger M, Molloy J, Tsara V, Shapiro CM, Douglas NJ (1988) Breathing pattern and eye movement density during REM sleep in humans. Am Rev Respir Dis 138:874–877

    Article  CAS  Google Scholar 

  35. Sei H (2012) Blood pressure surges in REM sleep: a mini review. Pathophysiology 19:233–241

    Article  Google Scholar 

  36. Cabiddu R, Cerutti S, Viardot G, Werner S, Bianchi AM (2012) Modulation of the sympatho-vagal balance during sleep: frequency domain study of heart rate variability and respiration. Front Physiol 3:45. doi: https://doi.org/10.3389/fphys.2012.00045

    Article  PubMed  PubMed Central  Google Scholar 

  37. Yasui Y, Cechetto DF, Saper CB (1990) Evidence for a cholinergic projection from the pedunculopontine tegmental nucleus to the rostral ventrolateral medulla in the rat. Brain Res 517:19–24

    Article  CAS  Google Scholar 

  38. Steininger TL, Rye DB, Wainer BH (1992) Afferent projections to the cholinergic pedunculopontine tegmental nucleus and adjacent midbrain extrapyramidal area in the albino rat. I. Retrograde tracing studies. J Comp Neurol 321:515–543

    Article  CAS  Google Scholar 

  39. Fink AM, Dean C, Piano MR, Carley DW (2017) The pedunculopontine tegmentum controls renal sympathetic nerve activity and cardiorespiratory activities in nembutal-anesthetized rats. PLoS One 12:e0187956

    Article  Google Scholar 

  40. Padley JR, Kumar NN, Li Q, Nguyen TB, Pilowsky PM, Goodchild AK (2007) Central command regulation of circulatory function mediated by descending pontine cholinergic inputs to sympathoexcitatory rostral ventrolateral medulla neurons. Circ Res 100:284–291

    Article  CAS  Google Scholar 

  41. Bourke SC, Gibson GJ (2002) Sleep and breathing in neuromuscular disease. Eur Respir J 19:1194–1201

    Article  CAS  Google Scholar 

  42. Somers VK, Dyken ME, Mark AL, Abboud FM (1993) Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med 328:303–307

    Article  CAS  Google Scholar 

  43. Nagura S, Sakagami T, Kakiichi A, Yoshimoto M, Miki K (2004) Acute shifts in baroreflex control of renal sympathetic nerve activity induced by REM sleep and grooming in rats. J Physiol 558:975–983

    Article  CAS  Google Scholar 

  44. Miki K, Kato M, Kajii S (2003) Relationship between renal sympathetic nerve activity and arterial pressure during REM sleep in rats. Am J Physiol Regul Integr Comp Physiol 284:R467–R473

    Article  CAS  Google Scholar 

  45. Naughton MT (2010) Loop gain in apnea: gaining control or controlling the gain? Am J Respir Crit Care Med 181:103–105

    Article  Google Scholar 

  46. Burgess KR (2012) New insights from the measurement of loop gain in obstructive sleep apnoea. J Physiol 590:1781–1782

    Article  CAS  Google Scholar 

  47. Fraigne JJ, Orem JM (2011) Phasic motor activity of respiratory and non-respiratory muscles in REM sleep. Sleep 34:425–434

    Article  Google Scholar 

  48. Vgontzas AN, Fernandez-Mendoza J, Liao D, Bixler EO (2013) Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev 17:241–254

    Article  Google Scholar 

  49. Jarrin DC, Ivers H, Lamy M, Chen IY, Harvey AG, Morin CM (2018) Cardiovascular autonomic dysfunction in insomnia patients with objective short sleep duration. J Sleep Res 27:e12663

    Article  Google Scholar 

  50. Tabaee Damavandi P, Dove MT, Pickersgill RW (2017) A review of drug therapy for sporadic fatal insomnia. Prion 11:293–299

    Article  CAS  Google Scholar 

  51. Benarroch EE, Stotz-Potter EH (1998) Dysautonomia in fatal familial insomnia as an indicator of the potential role of the thalamus in autonomic control. Brain Pathol 8:527–530

    Article  CAS  Google Scholar 

  52. Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK (2017) Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol 69:841–858

    Article  Google Scholar 

  53. Rosenzweig I, Williams SC, Morrell MJ (2014) The impact of sleep and hypoxia on the brain: potential mechanisms for the effects of obstructive sleep apnea. Curr Opin Pulm Med 20:565–571

    Article  Google Scholar 

  54. Salloum A, Rowley JA, Mateika JH, Chowdhuri S, Omran Q, Badr MS (2010) Increased propensity for central apnea in patients with obstructive sleep apnea: effect of nasal continuous positive airway pressure. Am J Respir Crit Care Med 181:189–193

    Article  Google Scholar 

  55. Gilmartin GS, Daly RW, Thomas RJ (2005) Recognition and management of complex sleep-disordered breathing. Curr Opin Pulm Med 11:485–493

    Article  Google Scholar 

  56. Onal E, Lopata M (1982) Periodic breathing and the pathogenesis of occlusive sleep apneas. Am Rev Respir Dis 126:676–680

    CAS  PubMed  Google Scholar 

  57. Guilleminault C, Poyares D, Rosa A, Huang YS (2005) Heart rate variability, sympathetic and vagal balance and EEG arousals in upper airway resistance and mild obstructive sleep apnea syndromes. Sleep Med 6:451–457

    Article  Google Scholar 

  58. Fletcher EC (2000) Cardiovascular consequences of obstructive sleep apnea: experimental hypoxia and sympathetic activity. Sleep 23[Suppl 4]:S127–S131

    PubMed  Google Scholar 

  59. Ferreira CB, Cravo SL, Stocker SD (2018) Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission. Physiol Rep 6:3. https://doi.org/10.14814/phy2.13536

    Article  CAS  Google Scholar 

  60. Prabhakar NR, Kumar GK (2010) Mechanisms of sympathetic activation and blood pressure elevation by intermittent hypoxia. Respir Physiol Neurobiol 174:156–161

    Article  Google Scholar 

  61. Mokhlesi B, Hagen EW, Finn LA, Hla KM, Carter JR, Peppard PE (2015) Obstructive sleep apnoea during REM sleep and incident non-dipping of nocturnal blood pressure: a longitudinal analysis of the Wisconsin Sleep Cohort. Thorax 70:1062–1069

    Article  Google Scholar 

  62. Costa-Silva JH, Zoccal DB, Machado BH (2012) Chronic intermittent hypoxia alters glutamatergic control of sympathetic and respiratory activities in the commissural NTS of rats. Am J Physiol Regul Integr Comp Physiol 302:R785–R793

    Article  CAS  Google Scholar 

  63. Fletcher EC, Bao G, Li R (1999) Renin activity and blood pressure in response to chronic episodic hypoxia. Hypertension 34:309–314

    Article  CAS  Google Scholar 

  64. Saponjic J, Radulovacki M, Carley DW (2003) Respiratory pattern modulation by the pedunculopontine tegmental nucleus. Respir Physiol Neurobiol 138:223–237

    Article  Google Scholar 

  65. Ni HF, Zhang JX, Harper RM (1990) Cardiovascular-related discharge of periaqueductal gray neurons during sleep–waking states. Brain Res 532:242–248

    Article  CAS  Google Scholar 

  66. Lin C, Lo M-T, Guilleminault C (2017) Exploring the abnormal modulation of the autonomic systems during nasal flow limitation in upper airway resistance syndrome by Hilbert–Huang transform. Front Med 4:161

    Article  Google Scholar 

  67. Palma JA, Urrestarazu E, Lopez-Azcarate J, Alegre M, Fernandez S, Artieda J, Iriarte J (2013) Increased sympathetic and decreased parasympathetic cardiac tone in patients with sleep related alveolar hypoventilation. Sleep 36:933–940

    Article  Google Scholar 

  68. Goodman BP (2018) Evaluation of postural tachycardia syndrome (POTS). Auton Neurosci. https://doi.org/10.1016/j.autneu.2018.04.004

    Article  PubMed  Google Scholar 

  69. Pengo MF, Higgins S, Drakatos P, Martin K, Gall N, Rossi GP, Leschziner G (2015) Characterisation of sleep disturbances in postural orthostatic tachycardia syndrome: a polysomnography-based study. Sleep Med 16:1457–1461

    Article  CAS  Google Scholar 

  70. Bagai K, Peltier A, Malow B, Diedrich A, Shibao C, Black B, Paranjape S, Orozco C, Biaggioni I, Robertson D, Raj S (2016) Objective sleep assessments in patients with postural tachycardia syndrome using overnight polysomnograms. J Clin Sleep Med 12:727–733

    Article  Google Scholar 

  71. Guilleminault C, Primeau M, Chiu HY, Yuen KM, Leger D, Metlaine A (2013) Sleep-disordered breathing in Ehlers–Danlos syndrome: a genetic model of OSA. Chest 144:1503–1511

    Article  Google Scholar 

  72. Manconi M, Ferri R, Zucconi M, Clemens S, Rundo F, Oldani A, Ferini-Strambi L (2011) Effects of acute dopamine-agonist treatment in restless legs syndrome on heart rate variability during sleep. Sleep Med 12:47–55

    Article  Google Scholar 

  73. Barone DA, Ebben MR, DeGrazia M, Mortara D, Krieger AC (2017) Heart rate variability in restless legs syndrome and periodic limb movements of sleep. Sleep Sci 10:80–86

    Article  Google Scholar 

  74. Chiaro G, Calandra-Buonaura G, Cecere A, Mignani F, Sambati L, Loddo G, Cortelli P, Provini F (2017) REM sleep behavior disorder, autonomic dysfunction and synuclein-related neurodegeneration: where do we stand? Clin Auton Res. doi: https://doi.org/10.1007/s10286-017-0460-4

  75. Sorensen GL, Kempfner J, Zoetmulder M, Sorensen HB, Jennum P (2012) Attenuated heart rate response in REM sleep behavior disorder and Parkinson’s disease. Mov Disord 27(7):888–894

    Article  Google Scholar 

  76. Berteotti C, Silvani A (2017) The link between narcolepsy and autonomic cardiovascular dysfunction: a translational perspective. Clin Auton Res. https://doi.org/10.1007/s10286-017-0473-z

    Article  PubMed  Google Scholar 

  77. Bastianini S, Silvani A, Berteotti C, Elghozi JL, Franzini C, Lenzi P, Lo Martire V, Zoccoli G (2011) Sleep related changes in blood pressure in hypocretin-deficient narcoleptic mice. Sleep 34:213–218

    Article  Google Scholar 

  78. Takahashi K, Lin JS, Sakai K (2008) Neuronal activity of orexin and non-orexin waking-active neurons during wake–sleep states in the mouse. Neuroscience 153:860–870

    Article  CAS  Google Scholar 

  79. Grimaldi D, Calandra-Buonaura G, Provini F, Agati P, Pierangeli G, Franceschini C, Barletta G, Plazzi G, Montagna P, Cortelli P (2012) Abnormal sleep-cardiovascular system interaction in narcolepsy with cataplexy: effects of hypocretin deficiency in humans. Sleep 35:519–528

    Article  Google Scholar 

  80. Sieminski M, Chwojnicki K, Sarkanen T, Partinen M (2017) The relationship between orexin levels and blood pressure changes in patients with narcolepsy. PLoS One 12:e0185975

    Article  Google Scholar 

  81. Fronczek R, Overeem S, Reijntjes R, Lammers GJ, van Dijk JG, Pijl H (2008) Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy. J Clin Sleep Med 4:248–254

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The first author is supported by the National Institute for Nursing Research (R00NR014369). The authors acknowledge Kevin Grandfield, Publication Manager, for editorial assistance.

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  1. Department of Biobehavioral Health Science, Sleep Neurobiology Laboratory, University of Illinois at Chicago College of Nursing, 845 South Damen Ave, Room 750 (MC 802), Chicago, IL, 60612, USA

    Anne M. Fink, Ulf G. Bronas & Michael W. Calik

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  1. Anne M. Fink
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  2. Ulf G. Bronas
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Correspondence to Anne M. Fink.

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Fink, A.M., Bronas, U.G. & Calik, M.W. Autonomic regulation during sleep and wakefulness: a review with implications for defining the pathophysiology of neurological disorders. Clin Auton Res 28, 509–518 (2018). https://doi.org/10.1007/s10286-018-0560-9

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