An Overview of Roles of the Basal Ganglia in Sleep-Wake Regulation

  • Wei-Min Qu
  • Ze Zhang
  • Huan-Ying Shi
  • Zhi-Li HuangEmail author


Sleep disorders are frequent in Parkinson’s disease and their prevalence increases with disease progression. Previous studies demonstrated that sleep disorders could appear as an initial manifestation of Parkinson’s disease even decades before motor signs, which highlight their clinical association in these early stages. Dysfunction of dopaminergic transmission in the basal ganglia involves in the pathogenesis of Parkinson’s disease and sleep disorders. This chapter will focus on reviewing the role of the basal ganglia in control of sleep and wakefulness.


Basal ganglia Dopamine Adenosine Sleep 


  1. 1.
    Videnovic A, Golombek D. Circadian and sleep disorders in Parkinson’s disease. Exp Neurol. 2013;243:45–56. Scholar
  2. 2.
    Lazarus M, Huang ZL, Lu J, Urade Y, Chen JF. How do the basal ganglia regulate sleep-wake behavior? Trends Neurosci. 2012;35(12):723–32. Scholar
  3. 3.
    Huang Z-L, Qu W-M, Eguchi N, Chen J-F, Schwarzschild MA, Fredholm BB, et al. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci. 2005;8(7):858–9.CrossRefGoogle Scholar
  4. 4.
    Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, et al. Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci. 2011;31(27):10067–75. Scholar
  5. 5.
    Crittenden JR, Graybiel AM. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments. Front Neuroanat. 2011;5:59.CrossRefGoogle Scholar
  6. 6.
    Qiu MH, Vetrivelan R, Fuller PM, Lu J. Basal ganglia control of sleep–wake behavior and cortical activation. Eur J Neurosci. 2010;31(3):499–507.CrossRefGoogle Scholar
  7. 7.
    Qiu M-H, Liu W, Qu W-M, Urade Y, Lu J, Huang Z-L. The role of nucleus accumbens core/shell in sleep-wake regulation and their involvement in Modafinil-induced arousal. PLoS One. 2012;7(9):e45471.CrossRefGoogle Scholar
  8. 8.
    Yadav RK, Khanday MA, Mallick BN. Interplay of dopamine and GABA in substantia nigra for the regulation of rapid eye movement sleep in rats. Behav Brain Res. 2019;376:112169. Scholar
  9. 9.
    Luo YJ, Li YD, Wang L, Yang SR, Yuan XS, Wang J, et al. Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors. Nat Commun. 2018;9(1):1576. Scholar
  10. 10.
    Ikemoto S. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex. Brain Res Rev. 2007;56(1):27–78.CrossRefGoogle Scholar
  11. 11.
    Sesack SR, Grace AA. Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology. 2009;35(1):27–47.CrossRefGoogle Scholar
  12. 12.
    Lena I, Parrot S, Deschaux O, Muffat-Joly S, Sauvinet V, Renaud B, et al. Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep–wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats. J Neurosci Res. 2005;81(6):891–9.CrossRefGoogle Scholar
  13. 13.
    Dong H, Wang J, Yang YF, Shen Y, Qu WM, Huang ZL. Dorsal striatum dopamine levels fluctuate across the sleep-wake cycle and respond to salient stimuli in mice. Front Neurosci. 2019;13:242. Scholar
  14. 14.
    Qu W-M, Xu X-H, Yan M-M, Wang Y-Q, Urade Y, Huang Z-L. Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice. J Neurosci. 2010;30(12):4382–9.CrossRefGoogle Scholar
  15. 15.
    Barik S, de Beaurepaire R. Dopamine D3 modulation of locomotor activity and sleep in the nucleus accumbens and in lobules 9 and 10 of the cerebellum in the rat. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005;29(5):718–26.CrossRefGoogle Scholar
  16. 16.
    Volkow ND, Tomasi D, Wang G-J, Telang F, Fowler JS, Logan J, et al. Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain. J Neurosci. 2012;32(19):6711–7.CrossRefGoogle Scholar
  17. 17.
    Tan E. Piribedil-induced sleep attacks in Parkinson’s disease. Fundam Clin Pharmacol. 2003;17(1):117–9.CrossRefGoogle Scholar
  18. 18.
    Lipford MC, Silber MH. Long-term use of pramipexole in the management of restless legs syndrome. Sleep Med. 2012;13(10):1280–5.CrossRefGoogle Scholar
  19. 19.
    Monti JM, Hawkins M, Jantos H, D’Angelo L, Fernández M. Biphasic effects of dopamine D-2 receptor agonists on sleep and wakefulness in the rat. Psychopharmacology. 1988;95(3):395–400.CrossRefGoogle Scholar
  20. 20.
    Sebban C, Zhang X, Tesolin-Decros B, Millan M, Spedding M. Changes in EEG spectral power in the prefrontal cortex of conscious rats elicited by drugs interacting with dopaminergic and noradrenergic transmission. Br J Pharmacol. 1999;128(5):1045–54.CrossRefGoogle Scholar
  21. 21.
    Murillo-Rodríguez E, Haro R, Palomero-Rivero M, Millán-Aldaco D, Drucker-Colín R. Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats. Behav Brain Res. 2007;176(2):353–7.CrossRefGoogle Scholar
  22. 22.
    Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001;21(5):1787–94.CrossRefGoogle Scholar
  23. 23.
    Qu W-M, Huang Z-L, Xu X-H, Matsumoto N, Urade Y. Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. J Neurosci. 2008;28(34):8462–9.CrossRefGoogle Scholar
  24. 24.
    Scammell T, Gerashchenko D, Mochizuki T, McCarthy M, Estabrooke I, Sears C, et al. An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons. Neuroscience. 2001;107(4):653–63.CrossRefGoogle Scholar
  25. 25.
    Satoh S, Matsumura H, Koike N, Tokunaga Y, Maeda T, Hayaishi O. Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist. Eur J Neurosci. 1999;11(5):1587–97.CrossRefGoogle Scholar
  26. 26.
    Durieux PF, Bearzatto B, Guiducci S, Buch T, Waisman A, Zoli M, et al. D2R striatopallidal neurons inhibit both locomotor and drug reward processes. Nat Neurosci. 2009;12(4):393–5.CrossRefGoogle Scholar
  27. 27.
    Oishi Y, Xu Q, Wang L, Zhang BJ, Takahashi K, Takata Y, et al. Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice. Nat Commun. 2017;8:734. Scholar
  28. 28.
    Yuan XS, Wang L, Dong H, Qu WM, Yang SR, Cherasse Y, et al. Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus. elife. 2017;6:6. Scholar
  29. 29.
    Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010;68(6):1023–42.CrossRefGoogle Scholar
  30. 30.
    Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437(7063):1257–63.CrossRefGoogle Scholar
  31. 31.
    Sherin J, Shiromani P, McCarley R, Saper C. Activation of ventrolateral preoptic neurons during sleep. Science. 1996;271(5246):216–9.CrossRefGoogle Scholar
  32. 32.
    Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron. 2001;30(2):345–54.CrossRefGoogle Scholar
  33. 33.
    Chuah YL, Venkatraman V, Dinges DF, Chee MW. The neural basis of interindividual variability in inhibitory efficiency after sleep deprivation. J Neurosci. 2006;26(27):7156–62.CrossRefGoogle Scholar
  34. 34.
    Muzur A, Pace-Schott EF, Hobson JA. The prefrontal cortex in sleep. Trends Cogn Sci. 2002;6(11):475–81.CrossRefGoogle Scholar
  35. 35.
    Chee MW, Choo WC. Functional imaging of working memory after 24 hr of total sleep deprivation. J Neurosci. 2004;24(19):4560–7.CrossRefGoogle Scholar
  36. 36.
    Koenigs M, Holliday J, Solomon J, Grafman J. Left dorsomedial frontal brain damage is associated with insomnia. J Neurosci. 2010;30(47):16041–3.CrossRefGoogle Scholar
  37. 37.
    Hur EE, Zaborszky L. Vglut2 afferents to the medial prefrontal and primary somatosensory cortices: a combined retrograde tracing in situ hybridization. J Comp Neurol. 2005;483(3):351–73.CrossRefGoogle Scholar
  38. 38.
    Yoshida K, McCormack S, España RA, Crocker A, Scammell TE. Afferents to the orexin neurons of the rat brain. J Comp Neurol. 2006;494(5):845–61.CrossRefGoogle Scholar
  39. 39.
    Sano H, Yokoi M. Striatal medium spiny neurons terminate in a distinct region in the lateral hypothalamic area and do not directly innervate orexin/hypocretin-or melanin-concentrating hormone-containing neurons. J Neurosci. 2007;27(26):6948–55.CrossRefGoogle Scholar
  40. 40.
    Usuda I, Tanaka K, Chiba T. Efferent projections of the nucleus accumbens in the rat with special reference to subdivision of the nucleus: biotinylated dextran amine study. Brain Res. 1998;797(1):73–93.CrossRefGoogle Scholar
  41. 41.
    Li C-S, Chung S, Lu D-P, Cho YK. Descending projections from the nucleus accumbens shell suppress activity of taste-responsive neurons in the hamster parabrachial nuclei. J Neurophysiol. 2012;108(5):1288–98.CrossRefGoogle Scholar
  42. 42.
    Heimer L, Zahm D, Churchill L, Kalivas P, Wohltmann C. Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience. 1991;41(1):89–125.CrossRefGoogle Scholar
  43. 43.
    Yang SR, Hu ZZ, Luo YJ, Zhao YN, Sun HX, Yin D, et al. The rostromedial tegmental nucleus is essential for non-rapid eye movement sleep. PLoS Biol. 2018;16(4):e2002909. Scholar
  44. 44.
    Deurveilher S, Lo H, Murphy JA, Burns J, Semba K. Differential c-Fos immunoreactivity in arousal-promoting cell groups following systemic administration of caffeine in rats. J Comp Neurol. 2006;498(5):667–89.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Wei-Min Qu
    • 1
    • 2
    • 3
  • Ze Zhang
    • 1
    • 2
    • 3
  • Huan-Ying Shi
    • 1
    • 2
    • 3
  • Zhi-Li Huang
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Pharmacology, School of Basic Medical SciencesFudan UniversityShanghaiChina
  2. 2.MOE Frontiers Center for Brain ScienceFudan UniversityShanghaiChina
  3. 3.Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Personalised recommendations