The sleep relay—the role of the thalamus in central and decentral sleep regulation

  • Philippe CoulonEmail author
  • Thomas Budde
  • Hans-Christian Pape
Invited Review


Surprisingly, the concept of sleep, its necessity and function, the mechanisms of action, and its elicitors are far from being completely understood. A key to sleep function is to determine how and when sleep is induced. The aim of this review is to merge the classical concepts of central sleep regulation by the brainstem and hypothalamus with the recent findings on decentral sleep regulation in local neuronal assemblies and sleep regulatory substances that create a scenario in which sleep is both local and use dependent. The interface between these concepts is provided by thalamic cellular and network mechanisms that support rhythmogenesis of sleep-related activity. The brainstem and the hypothalamus centrally set the pace for sleep-related activity throughout the brain. Decentral regulation of the sleep–wake cycle was shown in the cortex, and the homeostat of non-rapid-eye-movement sleep is made up by molecular networks of sleep regulatory substances, allowing individual neurons or small neuronal assemblies to enter sleep-like states. Thalamic neurons provide state-dependent gating of sensory information via their ability to produce different patterns of electrogenic activity during wakefulness and sleep. Many mechanisms of sleep homeostasis or sleep-like states of neuronal assemblies, e.g. by the action of adenosine, can also be found in thalamic neurons, and we summarize cellular and network mechanisms of the thalamus that may elicit non-REM sleep. It is argued that both central and decentral regulators ultimately target the thalamus to induce global sleep-related oscillatory activity. We propose that future studies should integrate ideas of central, decentral, and thalamic sleep generation.


Sleep Thalamus Cortex Brainstem Sleep–wake cycle NREMS Adenosine Nitric oxide Hypothalamus Homeostasis Hypothalamus Burst firing Neural network Rhythmogenesis 



The authors thank Ingrid Winkelhues for the assistance in the preparation of Fig. 1 and the reviewers for their helpful comments. The work reported of herein was enabled by grants to HCP (Max-Planck-Research Award 2007), TB (Interdisciplinary Centre for Clinical Research Münster, IZKF, Bud3/010/10; German Research Foundation, DFG, BU1019/8-1/9-2), and PC (Innovative Medical Research of the Medical Faculty Münster, CO 2 1 08 03 and CO 1 2 10 08).


  1. 1.
    Acuna-Goycolea C, Brenowitz SD, Regehr WG (2008) Active dendritic conductances dynamically regulate GABA release from thalamic interneurons. Neuron 57:420–431PubMedGoogle Scholar
  2. 2.
    Albrecht U (2011) Circadian rhythms and sleep - the metabolic connection. Pflugers Arch. doi:  10.1007/s00424-011-0986-6
  3. 3.
    Albrecht D, Quäschling U, Zippel U, Davidowa H (1996) Effects of dopamine on neurons of the lateral geniculate nucleus: an iontophoretic study. Synapse 23:70–78PubMedGoogle Scholar
  4. 4.
    Antal M, Acuna-Goycolea C, Pressler RT, Blitz DM, Regehr WG (2010) Cholinergic activation of M2 receptors leads to context-dependent modulation of feedforward inhibition in the visual thalamus. PLoS Biol 8:e1000348PubMedGoogle Scholar
  5. 5.
    Bal T, McCormick DA (1993) Mechanisms of oscillatory activity in guinea-pig nucleus reticularis thalami in vitro: a mammalian pacemaker. J Physiol (Lond) 468:669–691Google Scholar
  6. 6.
    Bal T, McCormick DA (1996) What stops synchronized thalamocortical oscillations? Neuron 17:297–308PubMedGoogle Scholar
  7. 7.
    Basheer R, Strecker RE, Thakkar MM, McCarley RW (2004) Adenosine and sleep–wake regulation. Progr Neurobiol 73:379–396Google Scholar
  8. 8.
    Batini C, Moruzzi G, Palestini M, Rossi G, Zanchetti A (1958) Presistent patterns of wakefulness in the pretrigeminal midpontine preparation. Science 128:30–32PubMedGoogle Scholar
  9. 9.
    Berger H (1929) Über das Elektrenkephalogramm des Menschen. Arch Psychiat Nervenkr 87:527–570Google Scholar
  10. 10.
    Berridge MJ (1998) Neuronal calcium signaling. Neuron 21:13–26PubMedGoogle Scholar
  11. 11.
    Blitz DM, Regehr WG (2005) Timing and specificity of feed-forward inhibition within the LGN. Neuron 45:917–928PubMedGoogle Scholar
  12. 12.
    Blumberg M, Karlsson K, Seelke A, Mohns E (2005) The ontogeny of mammalian sleep: a response to Frank and Heller (2003). J Sleep Res 14:91–98PubMedGoogle Scholar
  13. 13.
    Blumberg M, Seelke A, Lowen S, Karlsson K (2005) Dynamics of sleep–wake cyclicity in developing rats. PNAS 102:14860–14864PubMedGoogle Scholar
  14. 14.
    Broicher T, Kanyshkova T, Landgraf P, Rankovic V, Meuth P, Meuth SG, Pape HC, Budde T (2007) Specific expression of low-voltage-activated calcium channel isoforms and splice variants in thalamic local circuit interneurons. Mol Cell Neurosci 36:132–145PubMedGoogle Scholar
  15. 15.
    Broicher T, Kanyshkova T, Meuth P, Pape HC, Budde T (2008) Correlation of T-channel coding gene expression, IT, and the low threshold Ca2+ spike in the thalamus of a rat model of absence epilepsy. Mol Cell Neurosci 39:384–399PubMedGoogle Scholar
  16. 16.
    Broicher T, Wettschureck N, Munsch T, Coulon P, Meuth SG, Kanyshkova T, Seidenbecher T, Offermanns S, Pape HC, Budde T (2008) Muscarinic ACh receptor-mediated control of thalamic activity via G(q)/G(11)-family G-proteins. Pflugers Arch 456:1049–1060PubMedGoogle Scholar
  17. 17.
    Budde T, Biella G, Munsch T, Pape H-C (1997) Lack of regulation by intracellular Ca2+ of the hyperpolarization-activated cation current in rat thalamic neurons. J Physiol (Lond) 503(1):79–85Google Scholar
  18. 18.
    Budde T, Coulon P, Pawlowski M, Japes A, Meuth P, Meuth SG, Pape HC (2008) Reciprocal modulation of Ih and ITASK in thalamocortical relay neurons by halothane. Pflugers Arch 456:1061–1073PubMedGoogle Scholar
  19. 19.
    Budde T, Mager R, Pape H-C (1992) Different types of potassium outward current in relay neurons acutely isolated from the rat lateral geniculate nucleus. Eur J Neurosci 4:708–722PubMedGoogle Scholar
  20. 20.
    Budde T, Sieg F, Braunewell KH, Gundelfinger ED, Pape H-C (2000) Ca2+-induced Ca2+ release supports the relay mode of activity in thalamocortical cells. Neuron 26:483–492PubMedGoogle Scholar
  21. 21.
    Cain SM, Snutch TP (2010) Contributions of T-type calcium channel isoforms to neuronal firing. Channels 4:475–482PubMedGoogle Scholar
  22. 22.
    Campagna JA, Miller KW, Forman SA (2003) Mechanisms of actions of inhaled anesthetics. N Engl J Med 348:2110–2124PubMedGoogle Scholar
  23. 23.
    Coleman C, Baghdoyan H, Lydic R (2006) Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep. J Neurochem 96:1750–1759PubMedGoogle Scholar
  24. 24.
    Connors BW, Long MA (2004) Electrical synapses in the mammalian brain. Annu Rev Neurosci 27:393–418PubMedGoogle Scholar
  25. 25.
    Contreras D, Destexhe A, Sejnowski TJ, Steriade M (1996) Control of spatiotemporal coherence of a thalamic oscillation by corticothalamic feedback. Science 274:771–774PubMedGoogle Scholar
  26. 26.
    Contreras D, Steriade M (1996) Spindle oscillation in cats: the role of corticothalamic feedback in a thalamically generated rhythm. J Physiol (Lond) 490(1):159–179Google Scholar
  27. 27.
    Coulon P, Herr D, Kanyshkova T, Meuth P, Budde T, Pape H-C (2009) Burst discharges in neurons of the thalamic reticular nucleus are shaped by calcium-induced calcium release. Cell Calcium 46:333–346PubMedGoogle Scholar
  28. 28.
    Coulon P, Kanyshkova T, Broicher T, Munsch T, Wettschureck N, Seidenbecher T, Meuth SG, Offermanns S, Pape H-C, Budde T (2010) Activity modes in thalamocortical relay neurons are modulated by Gq/G11 family G-proteins-serotonergic and glutamatergic signalling. Front Cell Neurosci 4:1–10Google Scholar
  29. 29.
    Crandall SR, Govindaiah G, Cox CL (2010) Low-threshold Ca2+ current amplifies distal dendritic signaling in thalamic reticular neurons. J Neurosci 30:15419–15429PubMedGoogle Scholar
  30. 30.
    Crunelli V, Blethyn KL, Cope DW, Hughes SW, Parri HR, Turner JP, Tóth TI, Williams SR (2002) Novel neuronal and astrocytic mechanisms in thalamocortical loop dynamics. Philos Trans R Soc Lond B Biol Sci 357:1675–1693PubMedGoogle Scholar
  31. 31.
    Crunelli V, Cope DW, Hughes SW (2006) Thalamic T-type Ca2+ channels and NREM sleep. Cell Calcium 40:175–190PubMedGoogle Scholar
  32. 32.
    Crunelli V, Leresche N (1991) A role for GABAB receptors in excitation and inhibition of thalamocortical cells. TINS 14:16–21PubMedGoogle Scholar
  33. 33.
    Crunelli V, Lırincz ML, Errington AC, Hughes SW, (2011) Activity of cortical and thalamic neurons during the slow (<1 Hz) rhythm in the mouse in vivo. Pflugers Arch. doi:  10.1007/s00424-011-1011-9
  34. 34.
    Crunelli V, Tóth TI, Cope DW, Blethyn K, Hughes SW (2005) The ‘window’ T-type calcium current in brain dynamics of different behavioural states. J Physiol (Lond) 562:121–129Google Scholar
  35. 35.
    Cueni L, Canepari M, Lujan R, Emmenegger Y, Watanabe M, Bond CT, Franken P, Adelman JP, Luthi A (2008) T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites. Nat Neurosci 11:683–692PubMedGoogle Scholar
  36. 36.
    Currò Dossi RC, Nunez A, Steriade M (1992) Electrophysiology of a slow (0.5–4Hz) intrinsic oscillation of cat thalamocortical neurones in vivo. J Physiol (Lond) 447:215–234Google Scholar
  37. 37.
    Curró Dossi R, Paré D, Steriade M (1992) Various types of inhibitory postsynaptic potentials in anterior thalamic cells are differentially altered by stimulation of laterodorsal tegmental cholinergic nucleus. Neuroscience 47:279–289PubMedGoogle Scholar
  38. 38.
    Daum I, Leonard J, Hehl F (1988) Development of sleep during monotonous stimulation as related to individual differences. Integr Psychol Behav Sci 23:118–124Google Scholar
  39. 39.
    De Gennaro L, Ferrara M (2003) Sleep spindles: an overview. Sleep Med Rev 7:423–440PubMedGoogle Scholar
  40. 40.
    De Sarro G, Gareri P, Sinopoli VA, David E, Rotiroti D (1997) Comparative, behavioural and electrocortical effects of tumor necrosis factor-[alpha] and interleukin-1 microinjected into the locus coeruleus of rat. Life Sci 60:555–564PubMedGoogle Scholar
  41. 41.
    De A, Churchill L, Obal F, Simasko SM, Krueger JM (2002) GHRH and IL1[beta] increase cytoplasmic Ca2+ levels in cultured hypothalamic GABAergic neurons. Brain Res 949:209–212PubMedGoogle Scholar
  42. 42.
    Decrock E, Vinken M, Bol M, D’Herde K, Rogiers V, Vandenabeele P, Krysko DV, Bultynck G, Leybaert L (2011) Calcium and connexin-based intercellular communication, a deadly catch? Cell Calcium. doi: 10.1016/j.ceca.2011.05.007
  43. 43.
    Destexhe A, Babloyantz A, Sejnowski TJ (1993) Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons. Biophys J 65:1538–1552PubMedGoogle Scholar
  44. 44.
    Destexhe A, Bal T, Mccormick DA, Sejnowski TJ (1996) Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices. J Neurophysiol 76:2049–2070PubMedGoogle Scholar
  45. 45.
    Destexhe A, Contreras D, Sejnowski TJ, Steriade M (1994) A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J Neurophysiol 72:803–818PubMedGoogle Scholar
  46. 46.
    Diekelmann S, Born J (2010) The memory function of sleep. Nat Rev Neurosci 11:114–126PubMedGoogle Scholar
  47. 47.
    Ebert B, Wafford KA, Deacon S (2006) Treating insomnia: current and investigational pharmacological approaches. Pharmacol Ther 112:612–629PubMedGoogle Scholar
  48. 48.
    Errington AC, Connelly WM (2011) Dendritic T-type Ca2+ channels: giving a boost to thalamic reticular neurons. J Neurosci 31:5551–5553PubMedGoogle Scholar
  49. 49.
    Feldberg W, Sherwood SL (1954) Injections of drugs into the lateral ventricle of the cat. J Physiol (Lond) 123:148–167Google Scholar
  50. 50.
    Fitzpatrick D, Penny GR, Schmechel DE (1984) Glutamic acid decarboxylase-immunoreactive neurons and terminals in the lateral geniculate nucleus of the cat. J Neurosci 4:1809–1829PubMedGoogle Scholar
  51. 51.
    Fontanez D, Porter J (2006) Adenosine A1 receptors decrease thalamic excitation of inhibitory and excitatory neurons in the barrel cortex. Neuroscience 137:1177–1184PubMedGoogle Scholar
  52. 52.
    Francesconi W, Muller CM, Singer W (1988) Cholinergic mechanisms in the reticular control of transmission in the cat lateral geniculate nucleus. J Neurophysiol 59:1690–1718PubMedGoogle Scholar
  53. 53.
    Frank M, Heller H (2003) The ontogeny of mammalian sleep: a reappraisal of alternative hypotheses. J Sleep Res 12:25–34PubMedGoogle Scholar
  54. 54.
    Franks NP, Lieb WR (1994) Molecular and cellular mechanisms of general anaethesia. Nature 367:607–614PubMedGoogle Scholar
  55. 55.
    Franks NP, Lieb WR (1998) Which molecular targets are most relevant to general anaesthesia? Toxicol Lett 100–101:1–8PubMedGoogle Scholar
  56. 56.
    Fuentealba P, Steriade M (2005) The reticular nucleus revisited: intrinsic and network properties of a thalamic pacemaker. Progr Neurobiol 75:125–141Google Scholar
  57. 57.
    Gabbott PL, Somogyi J, Stewart MG, Hamori J (1986) A quantitative investigation of the neuronal composition of the rat dorsal lateral geniculate nucleus using GABA-immunocytochemistry. Neuroscience 19:101–111PubMedGoogle Scholar
  58. 58.
    Gastaut H, Bert J (1961) Electroencephalographic detection of sleep induced by repetitive sensory stimuli. In: Wolstenholme G, O’Connor C (eds) The Nature of Sleep. Churchill, London, pp 260–283Google Scholar
  59. 59.
    Gerashchenko D, Wisor JP, Burns D, Reh RK, Shiromani PJ, Sakurai T, de la Iglesia HO, Kilduff TS (2008) Identification of a population of sleep-active cerebral cortex neurons. PNAS 105:10227–10232PubMedGoogle Scholar
  60. 60.
    Graeff RM, Franco L, De Flora A, Lee HC (1998) Cyclic GMP-dependent and -independent effects on the synthesis of the calcium messengers cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate. J Biol Chem 273:118–125PubMedGoogle Scholar
  61. 61.
    Guillery R (1966) A study of Golgi preparations from the dorsal lateral geniculate nucleus of the adult cat. J Comp Neurol 128:21–50PubMedGoogle Scholar
  62. 62.
    Guillery RW, Feig SL, Lozsadi DA (1998) Paying attention to the thalamic reticular nucleus. Trends Neurosci 21:28–32PubMedGoogle Scholar
  63. 63.
    Guillery RW, Sherman SM (2002) Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system. Neuron 33:163–175PubMedGoogle Scholar
  64. 64.
    Haas HL, Lin, JS (2011) Waking with the hypothalamus. Pflugers Arch. doi:  10.1007/s00424-011-0996-4
  65. 65.
    Halassa MM (2011) Thalamocortical dynamics of sleep: roles of purinergic neuromodulation. Semin Cell Dev Biol 22(2):245–251Google Scholar
  66. 66.
    Huang Z-L, Urade Y, Hayaishi O (2007) Prostaglandins and adenosine in the regulation of sleep and wakefulness. Curr Opin Pharmacol 7:33–38PubMedGoogle Scholar
  67. 67.
    Huber R, Tononi G, Cirelli C (2007) Exploratory behavior, cortical BDNF expression, and sleep homeostasis. Sleep 30:129–139PubMedGoogle Scholar
  68. 68.
    Hughes SW, Cope DW, Crunelli V (1998) Dynamic clamp study of Ih modulation of burst firing and [delta] oscillations in thalamocortical neurons in vitro. Neuroscience 87:541–550PubMedGoogle Scholar
  69. 69.
    Huguenard JR, McCormick DA (2007) Thalamic synchrony and dynamic regulation of global forebrain oscillations. Trends Neurosci 30:350–356PubMedGoogle Scholar
  70. 70.
    Huguenard JR, Prince DA (1991) Slow inactivation of a TEA-sensitive K current in acutely isolated rat thalamic relay neurons. J Neurophysiol 66:1316–1328PubMedGoogle Scholar
  71. 71.
    Jahnsen H, Llinas R (1984) Electrophysiological properties of guinea-pig thalamic neurones: an in vitro study. J Physiol 349:205–226PubMedGoogle Scholar
  72. 72.
    Joksovic PM, Bayliss DA, Todorovic SM (2005) Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane. J Physiol (Lond) 566:125–142Google Scholar
  73. 73.
    Joksovic PM, Brimelow BC, Murbartián J, Perez-Reyes E, Todorovic SM (2005) Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Cav3.3 channels. Br J Pharmacol 144:59–70PubMedGoogle Scholar
  74. 74.
    Joksovic PM, Choe WJ, Nelson MT, Orestes P, Brimelow BC, Todorovic SM (2010) Mechanisms of inhibition of T-type calcium current in the reticular thalamic neurons by 1-octanol: implication of the protein kinase C pathway. Mol Pharmacol 77:87–94PubMedGoogle Scholar
  75. 75.
    Joksovic PM, Todorovic SM (2010) Isoflurane modulates neuronal excitability of the nucleus reticularis thalami in vitro. Ann NY Acad Sci 1199:36–42PubMedGoogle Scholar
  76. 76.
    Jones EG (1985) The thalamus. Plenum, New YorkGoogle Scholar
  77. 77.
    Jones EG (2002) Thalamic circuitry and thalamocortical synchrony. Philos Trans R Soc Lond B Biol Sci 357:1659–1673PubMedGoogle Scholar
  78. 78.
    Jouvet-Mounier D, Astic L, Lacote D (1970) Ontogenesis of the states of sleep in rat, cat, and guinea pig during the first postnatal month. Dev Psychobiol 2:216–239PubMedGoogle Scholar
  79. 79.
    Kanyshkova T, Broicher T, Meuth S, Pape H-C, Budde T (2011) A-type K+ currents in intralaminar thalamocortical relay neurons. Pflugers Arch 461:545–556PubMedGoogle Scholar
  80. 80.
    Kanyshkova T, Pawlowski M, Meuth P, Dubé C, Bender RA, Brewster AL, Baumann A, Baram TZ, Pape H-C, Budde T (2009) Postnatal expression pattern of HCN channel isoforms in thalamic neurons: relationship to maturation of thalamocortical oscillations. J Neurosci 29:8847–8857PubMedGoogle Scholar
  81. 81.
    Kasten MR, Rudy B, Anderson MP (2007) Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N-type calcium channels. J Physiol (Lond) 584:565–582Google Scholar
  82. 82.
    Kilduff TS, Cauli B, Gerashchenko D (2011) Activation of cortical interneurons during sleep: an anatomical link to homeostatic sleep regulation? Trends Neurosci 34:10–19PubMedGoogle Scholar
  83. 83.
    Kim U, Bal T, McCormick DA (1995) Spindle waves are propagating sychronized oscillations in the ferret LGNd in vitro. J Nuerophysiol 74:1301–1323Google Scholar
  84. 84.
    Koesling D, Humbert P, Schultz G (1995) The NO receptor: characterization and regulation of soluble guanylyl cyclase. In: Vincent SR (ed) Nitric oxide in the nervous system. Academic, London, pp 43–50Google Scholar
  85. 85.
    Krueger J, Churchill L, Rector D (2009) Cytokines and other neuromodulators. In: Stickgold R, Walker M (eds) The neuroscience of sleep. Elsevier, OxfordGoogle Scholar
  86. 86.
    Krueger JM, Rector DM, Roy S, Van Dongen HPA, Belenky G, Panksepp J (2008) Sleep as a fundamental property of neuronal assemblies. Nat Rev Neurosci 9:910–919PubMedGoogle Scholar
  87. 87.
    Landgraf D, Shostak A, Oster H (2011) Clock genes and sleep. Pflugers Arch. doi:  10.1007/s00424-011-1003-9
  88. 88.
    Landisman CE, Connors BW (2005) Long-term modulation of electrical synapses in the mammalian thalamus. Science 310:1809–1813PubMedGoogle Scholar
  89. 89.
    Landisman CE, Long MA, Beierlein M, Deans MR, Paul DL, Connors BW (2002) Electrical synapses in the thalamic reticular nucleus. J Neurosci 22:1002–1009PubMedGoogle Scholar
  90. 90.
    Lee SH, Govindaiah G, Cox CL (2007) Heterogeneity of firing properties among rat thalamic reticular nucleus neurons. J Physiol 582:195–208PubMedGoogle Scholar
  91. 91.
    Llinas R, Ribary U (1993) Coherent 40-Hz oscillation characterizes dream state in humans. PNAS 90:2078–2081PubMedGoogle Scholar
  92. 92.
    Llinas RR, Steriade M (2006) Bursting of thalamic neurons and states of vigilance. J Neurophysiol 95:3297–3308PubMedGoogle Scholar
  93. 93.
    Ludwig A, Budde T, Stieber J, Moosmang S, Wahl C, Holthoff K, Langebartels A, Wotjak C, Munsch T, Zong X, Feil S, Feil R, Lancel M, Chien KR, Konnerth A, Pape HC, Biel M, Hofmann F (2003) Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2. EMBO J 22:216–224PubMedGoogle Scholar
  94. 94.
    Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M (1998) A family of hyperpolarization-activated mammalian cation channels. Nature 393:587–591PubMedGoogle Scholar
  95. 95.
    Lüthi A, McCormick DA (1999) Modulation of a pacemaker current through Ca2+-induced stimulation of cAMP production. Nat Neurosci 2:634–641PubMedGoogle Scholar
  96. 96.
    Magni F, Moruzzi G, Rossi G, Zanchetti A (1959) EEG arousal following inactivation of the lower brain stem by selective injection of barbiturate into the vertebral circulation. Arch Ital Biol 97:33–46Google Scholar
  97. 97.
    Mancia M, Margnelli M, Mariotti M, Spreafico R, Broggi G (1974) Brain stem-thalamus reciprocal influences in the cat. Brain Res 69:297–314PubMedGoogle Scholar
  98. 98.
    Mancia M, Meulders M, Santibanez H (1959) Synchronisation de l’électroencéphalogramme provoquée par la stimulation visuelle répétitive chez le chat “médiopontin prétrigéminal”. Arch Int Physiol Biochem 67:661–670Google Scholar
  99. 99.
    Manfridi A, Brambilla D, Bianchi S, Mariotti M, Opp MR, Imeri L (2003) Interleukin-1β enhances non-rapid eye movement sleep when microinjected into the dorsal raphe nucleus and inhibits serotonergic neurons in vitro. Eur J Neurosci 18:1041–1049PubMedGoogle Scholar
  100. 100.
    Mares P, Maresová D, Trojan S, Fischer J (1982) Ontogenetic development of rhythmic thalamo-cortical phenomena in the rat. Brain Res Bull 8:765–769PubMedGoogle Scholar
  101. 101.
    Marks GA, Birabil CG (1998) Enhancement of rapid eye movement sleep in the rat by cholinergic and adenosinergic agonists infused into the pontine reticular formation. Neuroscience 86:29–37PubMedGoogle Scholar
  102. 102.
    Marshall L, Born J (2007) The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn Sci 11:442–450PubMedGoogle Scholar
  103. 103.
    Martinowich K, Schloesser R, Jimenez D, Weinberger D, Lu B (2011) Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior. Mol Brain 4:11PubMedGoogle Scholar
  104. 104.
    Matos G, Andersen ML, do Valle AC, Tufik S (2010) The relationship between sleep and epilepsy: evidence from clinical trials and animal models. J Neurol Sci 295:1–7PubMedGoogle Scholar
  105. 105.
    McCormick DA (1992) Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog Neurobiol 39:337–388PubMedGoogle Scholar
  106. 106.
    McCormick DA (1992) Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus. J Neurosci 12:278–289PubMedGoogle Scholar
  107. 107.
    McCormick DA, Bal T (1994) Sensory gating mechanisms of the thalamus. Curr Opin Neurobiol 4:550–556PubMedGoogle Scholar
  108. 108.
    McCormick DA, Bal T (1997) Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci 20:185–215PubMedGoogle Scholar
  109. 109.
    McCormick DA, Pape H-C (1988) Acetylcholine inhibits identified interneurons in the cat lateral geniculate nucleus. Nature 334:246–248PubMedGoogle Scholar
  110. 110.
    McCormick DA, Pape HC (1990) Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones. J Physiol (Lond) 431:291–318Google Scholar
  111. 111.
    McCormick DA, Pape HC (1990) Noradrenergic and serotonergic modulation of a hyperpolarization-activated cation current in thalamic relay neurones. J Physiol (Lond) 431:319–342Google Scholar
  112. 112.
    McGinty D, Sterman M (1968) Sleep suppression after basal forebrain lesions in the cat. Science 160:1253–1255PubMedGoogle Scholar
  113. 113.
    Meuth SG, Kanyshkova T, Meuth P, Landgraf P, Munsch T, Ludwig A, Hofmann F, Pape HC, Budde T (2006) Membrane resting potential of thalamocortical relay neurons is shaped by the interaction among TASK3 and HCN2 channels. J Neurophysiol 96:1517–1529PubMedGoogle Scholar
  114. 114.
    Mignot E, Lin L (2009) Narcolepsy. In: Stickgold R, Walker M (eds) The Neuroscience of Sleep. Elsevier, pp 270–277Google Scholar
  115. 115.
    Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL (1997) Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors. Nature 389:385–389PubMedGoogle Scholar
  116. 116.
    Montero V, Singer W (1985) Ultrastructural identification of somata and neural processes immunoreactive to antibodies against glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the cat. Exp Brain Res 59:151–165PubMedGoogle Scholar
  117. 117.
    Monti JM, Monti D (2007) The involvement of dopamine in the modulation of sleep and waking. Sleep Med Rev 11:113–133PubMedGoogle Scholar
  118. 118.
    Moruzzi G (1972) The sleep–waking cycle. Ergeb Physiol 64:1–165PubMedGoogle Scholar
  119. 119.
    Moruzzi G, Magoun H (1949) Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1:455–473PubMedGoogle Scholar
  120. 120.
    Mullington J (2009) Endocrine function during sleep and sleep deprivation. In: Stickgold R, Walker M (eds) The Neuroscience of Sleep. Elsevier, pp 209–212Google Scholar
  121. 121.
    Mullington J (2009) Immune function during sleep and sleep deprivation. In: Stickgold R, Walker M (eds) The Neuroscience of Sleep. Elsevier, pp 213–217Google Scholar
  122. 122.
    Munsch T, Budde T, Pape HC (1997) Voltage-activated intracellular calcium transients in thalamic relay cells and interneurons. Neuroreport 8:2411–2418PubMedGoogle Scholar
  123. 123.
    Munsch T, Yanagawa Y, Obata K, Pape HC (2005) Dopaminergic control of local interneuron activity in the thalamus. Eur J Neurosci 21:290–294PubMedGoogle Scholar
  124. 124.
    Nauta W (1946) Hypothalamic regulation of sleep in rats; an experimental study. J Neurophysiol 9:285–316PubMedGoogle Scholar
  125. 125.
    Nelson LE, Guo TZ, Lu J, Saper CB, Franks NP, Maze M (2002) The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway. Nat Neurosci 5:979–984PubMedGoogle Scholar
  126. 126.
    Nishino S (2009) Cataplexy. In: Stickgold R, Walker M (eds) The Neuroscience of Sleep. Elsevier, pp 278–284Google Scholar
  127. 127.
    Obal FJ, Krueger J (2003) Biochemical regulation of non-rapid-eye-movement sleep. Front Biosci 8:d520–d550PubMedGoogle Scholar
  128. 128.
    Ohara PT, Lieberman AR (1985) The thalamic reticular nucleus of the adult rat: experimental anatomical studies. J Neurocytol 14:365–411PubMedGoogle Scholar
  129. 129.
    Ohara PT, Lieberman AR, Hunt SP, Wu JY (1983) Neural elements containing glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the rat; Immunohistochemical studies by light and electron microscopy. Neuroscience 8:189–211PubMedGoogle Scholar
  130. 130.
    Oishi Y, Huang Z-L, Fredholm BB, Urade Y, Hayaishi O (2008) Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non-rapid eye movement sleep. PNAS 105:19992–19997PubMedGoogle Scholar
  131. 131.
    Pace-Schott EF, Hobson JA (2002) The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 3:591–605PubMedGoogle Scholar
  132. 132.
    Pape H-C (1992) Adenosine promotes burst activity in guinea-pig geniculocortical neurones through two different ionic mechanisms. J Physiol (Lond) 447:729–753Google Scholar
  133. 133.
    Pape HC (1996) Queer current and pacemaker: the hyperpolarization-activated cation current in neurons. Annu Rev Physiol 58:299–327PubMedGoogle Scholar
  134. 134.
    Pape H-C, Budde T, Mager R, Kisvarday Z (1994) Prevention of Ca2+-mediated action potentials in GABAergic local circuit neurons of the thalamus by a transient K+ current. J Physiol (Lond) 478(3):403–422Google Scholar
  135. 135.
    Pape H-C, Mager R (1992) Nitric oxide controls oscillatory activity in thalamocortical neurons. Neuron 9:441–448PubMedGoogle Scholar
  136. 136.
    Pape HC, McCormick DA (1989) Noradrenaline and serotonin selectively modulate thalamic burst firing by enhancing a hyperpolarization-activated cation current. Nature 340:715–718PubMedGoogle Scholar
  137. 137.
    Pape HC, McCormick DA (1995) Electrophysiological and pharmacological properties of interneurons in the cat dorsal lateral geniculate nucleus. Neuroscience 68:1105–1125PubMedGoogle Scholar
  138. 138.
    Pape HC, Munsch T, Budde T (2004) Novel vistas of calcium-mediated signalling in the thalamus. Eur J Physiol (Pflügers Arch) 448:131–138Google Scholar
  139. 139.
    Parri HR, Crunelli V (2001) Pacemaker calcium oscillations in thalamic astrocytes in situ. Neuroreport 12:3897–3900PubMedGoogle Scholar
  140. 140.
    Parri HR, Gould TM, Crunelli V (2001) Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation. Nat Neurosci 4:803–812PubMedGoogle Scholar
  141. 141.
    Perez Velazquez JL, Carlen PL (1996) Development of firing patterns and electrical properties in neurons of the rat ventrobasal thalamus. Brain Res 91:164–170Google Scholar
  142. 142.
    Pinault D (2004) The thalamic reticular nucleus: structure, function and concept. Brain Res Brain Res Rev 46:1–31PubMedGoogle Scholar
  143. 143.
    Pinault D, Deschênes M (1998) Projection and innervation patterns of individual thalamic reticular axons in the thalamus of the adult rat: a three-dimensional, graphic, and morphometric analysis. J Comp Neurol 391:180–203PubMedGoogle Scholar
  144. 144.
    Porkka-Heiskanen T (2011) Methylxanthines and sleep. In: Fredholm BB (ed) Methylxanthines, handbook of experimental pharmacology. Springer, Berlin, Heidelberg, pp 331–348Google Scholar
  145. 145.
    Porkka-Heiskanen T, Alanko L, Kalinchuk A, Stenberg D (2002) Adenosine and sleep. Sleep Med Rev 6:321–332PubMedGoogle Scholar
  146. 146.
    Porkka-Heiskanen T, Kalinchuk A (2011) Adenosine, energy metabolism and sleep homeostasis. Sleep Med Rev 15:123–135PubMedGoogle Scholar
  147. 147.
    Puizillout J, Ternaux J, Foutz A, Dell P (1973) Slow wave sleep with phasic discharges. Triggering by vago-aortic stimulation. Rev Electroencephalogr Neurophysiol Clin 3(21–37):143Google Scholar
  148. 148.
    Rainnie DG, Grunze HCR, McCarley RW, Greene RW (1994) Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG arousal. Science 263(689–692):144Google Scholar
  149. 149.
    Rechtschaffen A, Bergmann B (2002) Sleep deprivation in the rat: an update of the 1989 paper. Sleep 25:18–24PubMedGoogle Scholar
  150. 150.
    Rechtschaffen A, Kales A (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subject. U.S. National Institute of Neurological Diseases and Blindness, Neurological Information Network, Bethesda, MDGoogle Scholar
  151. 151.
    Reinoso-Suárez F, De Andrés I, Garzón M (2011) Functional anatomy of the sleep–wakefulness cycle: wakefulness. Adv Anat Embryol Cell Biol 208(1–128):147Google Scholar
  152. 152.
    Richter TA, Kolaj M, Renaud LP (2005) Low voltage-activated Ca2+ channels are coupled to Ca2+-induced Ca2+ release in rat thalamic midline neurons. J Neurosci 25(8267–8271):148Google Scholar
  153. 153.
    Ries CR, Puil E (1999) Ionic mechanism of isoflurane’s actions on thalamocortical neurons. J Neurophysiol 81:1802–1809PubMedGoogle Scholar
  154. 154.
    Ries CR, Puil E (1999) Mechanism of anesthesia revealed by shunting actions of isoflurane on thalamocortical neurons. J Neurophysiol 81:1795–1801PubMedGoogle Scholar
  155. 155.
    Rosenberg PA, Li Y, Le M, Zhang Y (2000) Nitric oxide-stimulated increase in extracellular adenosine accumulation in rat forebrain neurons in culture is associated with atp hydrolysis and inhibition of adenosine kinase activity. J Neurosci 20:6294–6301PubMedGoogle Scholar
  156. 156.
    Sallanon M, Denoyer M, Kitahama K, Aubert C, Gay N, Jouvet M (1989) Long-lasting insomnia induced by preoptic neuron lesions and its transient reversal by muscimol injection into the posterior hypothalamus in the cat. Neuroscience 32:669–683PubMedGoogle Scholar
  157. 157.
    Salt TE (2002) Glutamate receptor functions in sensory relay in the thalamus. Philos Trans R Soc Lond B Biol Sci 357:1759–1766PubMedGoogle Scholar
  158. 158.
    Seelke A, Blumberg M (2008) The microstructure of active and quiet sleep as cortical delta activity emerges in infant rats. Sleep 31:691–699PubMedGoogle Scholar
  159. 159.
    Selbach O, Haas HL (2006) Hypocretins: the timing of sleep and waking. Chronobiol Int 23(1–2):63–70Google Scholar
  160. 160.
    Shaw PJ, Salt TE (1997) Modulation of sensory and excitatory amino acid responses by nitric oxide donors and glutathione in the ventrobasal thalamus of the rat. Eur J Neurosci 9:1507–1513PubMedGoogle Scholar
  161. 161.
    Sherman SM (2001) Tonic and burst firing: dual modes of thalamocortical relay. Trends Neurosci 24:122–126PubMedGoogle Scholar
  162. 162.
    Sherman SM (2007) The thalamus is more than just a relay. Curr Opin Neurobiol 17:417–422PubMedGoogle Scholar
  163. 163.
    Sherman SM, Guillery RW (1996) Functional organization of thalamocortical relays. J Neurophysiol 76(3):1367–1395Google Scholar
  164. 164.
    Sherman SM, Guillery RW (2006) Exploring the thalamus and its role in cortical function. MIT Press, CambridgeGoogle Scholar
  165. 165.
    Sieg F, Obst K, Gorba T, Riederer B, Pape HC, Wahle P (1998) Postnatal expression pattern of calcium-binding proteins in organotypic thalamic cultures and in the dorsal thalamus in vivo. Brain Res 110:83–95Google Scholar
  166. 166.
    Singer W (1977) Control of thalamic transmission by corticofugal and ascending reticular pathways in the visual system. Physiol Rev 57:386–420PubMedGoogle Scholar
  167. 167.
    Soltesz I, Lightowler S, Leresche N, Jassik-Gerschenfeld D, Pollard CE, Crunelli V (1991) Two inward currents and the transformation of low-frequency oscillations of rat and cat thalamocortical cells. J Physiol (Lond) 441:175–197Google Scholar
  168. 168.
    Spreafico R, Battaglia G, Frassoni C (1991) The reticular thalamic nucleus (RTN) of the rat: cytoarchitectural, Golgi, immunocytochemical, and horseradish peroxidase study. J Comp Neurol 304:478–490PubMedGoogle Scholar
  169. 169.
    Spreafico R, de Curtis M, Frassoni C, Avanzini G (1988) Electrophysiological characteristics of morphologically identified reticular thalamic neurons from rat slices. Neuroscience 27:629–638PubMedGoogle Scholar
  170. 170.
    Stenberg D (2007) Cell Mol Life Sci 64:1187–1204PubMedGoogle Scholar
  171. 171.
    Steriade M (2006) Grouping of brain rhythms in corticothalamic systems. Neuroscience 137:1087–1106PubMedGoogle Scholar
  172. 172.
    Steriade M, Curro Dossi RC, Nunez A (1991) Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: cortically induced synchronization and brainstem cholinergic suppression. J Neurosci 11:3200–3217PubMedGoogle Scholar
  173. 173.
    Steriade M, Domich L, Oakson G (1986) Reticularis thalami neurons revisited: activity changes during shifts in states of vigilance. J Neurosci 6:68–81PubMedGoogle Scholar
  174. 174.
    Steriade M, Domich L, Oakson G, Deschenes M (1987) The deafferented reticular thalamic nucleus generates spindle rhythmicity. J Neurophysiol 57:260–273PubMedGoogle Scholar
  175. 175.
    Steriade M, Jones EG, McCormick DA (1997) Thalamus. Elsevier, AmsterdamGoogle Scholar
  176. 176.
    Steriade M, McCarley R (1990) Brainstem control of wakefulness and sleep. Plenum, New YorkGoogle Scholar
  177. 177.
    Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262:679–685PubMedGoogle Scholar
  178. 178.
    Steriade M, Pare D, Hu B, Deschenes M (1990) The visual thalamocortical system and its modulation by the brain stem core. Prog Sens Physiol 10:1–124Google Scholar
  179. 179.
    Stocker M, Pedarzani P (2000) Differential distribution of three Ca2+-activated K+ channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system. Mol Cell Neurosci 15:476–493PubMedGoogle Scholar
  180. 180.
    Szymusiak R (2009) Thermoregulation during sleep and sleep deprivation. In: Stickgold R, Walker M (eds) The Neuroscience of Sleep. Elsevier, pp 218–222Google Scholar
  181. 181.
    Terman D, Bose A, Kopell N (1996) Functional reorganization in thalamocortical networks: transition between spindling and delta sleep rhythms. PNAS 93:15417–15422PubMedGoogle Scholar
  182. 182.
    Todorovic SM, Lingle CJ (1998) Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents. J Neurophysiol 79:240–252PubMedGoogle Scholar
  183. 183.
    Tóth TI, Crunelli V (1997) Simulation of intermittent action potential firing in thalamocortical neurons. Neuroreport 8:2889–2892PubMedGoogle Scholar
  184. 184.
    Tscherter A, David F, Ivanova T, Deleuze C, Renger JJ, Uebele VN, Shin HS, Bal T, Leresche N, Lambert RC (2011) Minimal alterations in T-type calcium channel gating markedly modify physiological firing dynamics. J Physiol (Lond) 589:1707–1724Google Scholar
  185. 185.
    Van Dort CJ, Baghdoyan HA, Lydic R (2009) Adenosine A1 and A2A receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci 29:871–881PubMedGoogle Scholar
  186. 186.
    Veasey S (2009) Sleep apnea. In: Stickgold R, Walker M (eds) The Neuroscience of Sleep. Elsevier, pp 263–269Google Scholar
  187. 187.
    Villablanca J (2004) Counterpointing the functional role of the forebrain and of the brainstem in the control of the sleep-waking system. J Sleep Res 13:179–208PubMedGoogle Scholar
  188. 188.
    Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G (2011) Local sleep in awake rats. Nature 472:443–447PubMedGoogle Scholar
  189. 189.
    Wan X, Mathers DA, Puil E (2003) Pentobarbital modulates intrinsic and GABA-receptor conductances in thalamocortical inhibition. Neuroscience 121:947–958PubMedGoogle Scholar
  190. 190.
    Ward C (2011) On doing nothing: descriptions of sleep, fatigue, and motivation in encephalitis lethargica. Mov Disord. doi: 10.1002/mds.23545, Epub ahead of print
  191. 191.
    Wurtz RH, Sommer MA, Cavanaugh J (2005) Drivers from the deep: the contribution of collicular input to thalamocortical processing. Prog Brain Res 149:207–225PubMedGoogle Scholar
  192. 192.
    Yang S, Cox CL (2007) Modulation of inhibitory activity by nitric oxide in the thalamus. J Neurophysiol 97:3386–3395PubMedGoogle Scholar
  193. 193.
    Yang S, Cox CL (2008) Excitatory and anti-oscillatory actions of nitric oxide in thalamus. J Physiol (Lond) 586:3617–3628Google Scholar
  194. 194.
    Ying SW, Goldstein PA (2005) Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABA(A) receptor chloride channels. Mol Pain 1:2PubMedGoogle Scholar
  195. 195.
    Zeitlhofer J, Gruber G, Anderer P, Asenbaum S, Schimicek P, Saletu B (1997) Topographic distribution of sleep spindles in young healthy subjects. J Sleep Res 6:149–155PubMedGoogle Scholar
  196. 196.
    Zhao Y, Kerscher N, Eysel U, Funke K (2002) D1 and D2 receptor-mediated dopaminergic modulation of visual responses in cat dorsal lateral geniculate nucleus. J Physiol (Lond) 539:223–238Google Scholar
  197. 197.
    Zhu JJ, Uhlrich DJ, Lytton WW (1999) Burst firing in identified rat geniculate interneurons. Neuroscience 91:1445–1460PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Philippe Coulon
    • 1
    Email author
  • Thomas Budde
    • 1
  • Hans-Christian Pape
    • 1
  1. 1.Institut für Physiologie IWestfälische Wilhelms-Universität MünsterMünsterGermany

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