Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Sleep as a fundamental property of neuronal assemblies

Nature Reviews Neuroscience volume 9, pages 910–919 (2008)Cite this article

Key Points

  • Sleep is a fundamental property of neuronal assemblies such as cortical columns.

  • Sleep is regulated in a neuronal-assembly use-dependent manner.

  • The mechanisms that underlie neuronal-assembly sleep include enhanced activity of sleep-regulatory substances, induced by neuronal use-enhanced metabolism.

  • A mathematical model of loosely connected neuronal assemblies shows that they synchronize their sleep-like and awake-like states.

  • Sleep probably evolved from a metabolically quiescent rest state.

  • Sleep seems to function to stabilize instinctual and learned memories.

Abstract

Sleep is vital to cognitive performance, productivity, health and well-being. Earlier theories of sleep presumed that it occurred at the level of the whole organism and that it was governed by central control mechanisms. However, evidence now indicates that sleep might be regulated at a more local level in the brain: it seems to be a fundamental property of neuronal networks and is dependent on prior activity in each network. Such local-network sleep might be initiated by metabolically driven changes in the production of sleep-regulatory substances. We discuss a mathematical model which illustrates that the sleep-like states of individual cortical columns can be synchronized through humoral and electrical connections, and that whole-organism sleep occurs as an emergent property of local-network interactions.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Molecular networks of sleep-regulatory substances make up the non-rapid-eye-movement sleep homeostat.
Figure 2: Translation of neurotransmission into actions of sleep-regulatory substances.
Figure 3: Activity-driven changes in sleep-regulatory substances regulate sleep at the local level.

References

  1. Koella, W. P. The organization and regulation of sleep. A review of the experimental evidence and a novel integrated model of the organizing and regulating apparatus. Experientia 40, 309–338 (1984).

    Article  CAS  PubMed  Google Scholar 

  2. Panksepp, J., Jalowiec, J. E., Zolovick, A. J., Stern, W. C. & Morgane, P. J. Inhibition of glycolytic metabolism and sleep-waking states in cats. Pharm. Biochem. Behav. 1, 41–46 (1973).

    Article  Google Scholar 

  3. Jouvet, M. Biogenic amines and the states of sleep. Science 163, 32–41 (1969).

    Article  CAS  PubMed  Google Scholar 

  4. Krueger, J. M. & Obal, F. Jr. A neuronal group theory of sleep function. J. Sleep Res. 2, 63–69 (1993). This was the first statement of the hypothesis that sleep is a local use-dependent process.

    Article  CAS  PubMed  Google Scholar 

  5. Krueger, J. M. & Obal, F. Jr. Sleep function. Front. Biosci. 8, 511–519 (2003).

    Article  Google Scholar 

  6. Rector, D. M., Topchiy, I. A., Carter, K. M. & Rojas, M. J. Local functional state differences between rat cortical columns. Brain Res. 1047, 45–55 (2005). This was the first demonstration that cortical columns oscillate between functional states, one of which has properties similar to whole-organism sleep.

    Article  CAS  PubMed  Google Scholar 

  7. Mahowald, M. W. & Schenck, C. H. Insights from studying human sleep disorders. Nature 437, 1279–1285 (2005). These authors have recognized for over 20 years that human parasomnias suggest that the brain can be awake and asleep simultaneously. This is a comprehensive review of that work.

    Article  CAS  PubMed  Google Scholar 

  8. Mukhametov, L. M., Supin, A. Y. & Polyakova, I. G. Interhemispheric asymmetry of the electroencephalographic sleep patterns in dolphins. Brain Res. 134, 581–584 (1977). This pioneering study demonstrated that dolphins have high-amplitude delta-wave sleep in only one half of the brain at a time, and that they lack REMS.

    CAS  Google Scholar 

  9. Rattenborg, N. C., Amlaner, C. J. & Lima, S. L. Unilateral eye closure and interhemispheric EEG asymmetry during sleep in the pigeon (Columba livia). Brain Behav. Evol. 58, 323–332 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Werth, E., Achermann, P., Dijk, D. J. & Borbely, A. A. Spindle frequency activity in the sleep EEG: individual differences and topographic distribution. Electroencephalogr. Clin. Neurophysiol. 103, 535–542 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Braun, A. R. et al. Regional cerebral blood flow throughout the sleep-wake cycle. An H215O PET study. Brain 120, 1173–1197 (1997).

    Article  PubMed  Google Scholar 

  12. Kristiansen, K. & Courtois, G. Rhythmic activity from isolated cerebral cortex EEG. Clin. Neurophysiol. 1, 265–272 (1949).

    Article  CAS  Google Scholar 

  13. Steriade, M. The corticothalamic system in sleep. Front. Biosci. 8, d878–d899 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Pigarev, I. N., Nothdurf, H. C. & Kastner, S. Evidence for asynchronous development of sleep in cortical areas. Neuroreport 8, 2557–2560 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Koch, C. The Quest for Consciousness (Roberts and Company, Englewood, Colarado, 2004).

    Google Scholar 

  16. Walker, A. J., Topchiy, I., Kouptsov, K. & Rector, D. M. ERP differences during conditioned lick response in the rat. Sleep 28, A15 (2005).

    Google Scholar 

  17. Moore, R. Y. Suprachiasmatic nucleus in sleep-wake regulation. Sleep Med. 8 (Suppl. 3), 27–33 (2007).

    Google Scholar 

  18. Kattler, H., Dijk, D. J. & Borbely, A. A. Effect of unilateral somatosensory stimulation prior to sleep on the sleep EEG in humans. J. Sleep Res. 3, 1599–1604 (1994). The authors tested the hypothesis put forward in reference 4 that sleep is a local activity-dependent process. Much research has since extended and confirmed this pioneering study.

    Article  Google Scholar 

  19. Miyamoto, H., Katagiri, H. & Hensch, T. Experience-dependent slow-wave sleep development. Nature Neurosci. 6, 553–554 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Iwasaki, N., Karashima, A., Tamakawa, Y., Katayama, N. & Nakao, M. Sleep EEG dynamics in rat barrel cortex associated with sensory deprivation. Neuroreport 15, 2681–2684 (2004).

    Article  PubMed  Google Scholar 

  21. Vyazovskiy, V., Borbely, A. A. & Tobler, I. Unilateral vibrissae stimulation during waking induces interhemispheric EEG asymmetry during subsequent sleep in the rat. J. Sleep Res. 9, 367–371 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Cottone, L. A., Adamo, D. & Squires, N. K. The effect of unilateral somatosensory stimulation on hemispheric asymmetries during slow wave sleep. Sleep 27, 63–68 (2004).

    Article  PubMed  Google Scholar 

  23. Ferrara, M., De Gennaro, L., Curcio, G., Cristiani, R. & Bertini, M. Interhemispheric asymmetry of human sleep EEG in response to selective slow-wave sleep deprivation. Behav. Neurosci. 116, 976–981 (2002).

    Article  PubMed  Google Scholar 

  24. Huber, R., Ghilardi, M. F., Massimini, M. & Tononi, G. Local sleep and learning. Nature 430, 78–81 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Yasuda, T., Yasuda, K., Brown, R. A. & Krueger, J. M. State-dependent effects of light-dark cycle on somatosensory and visual cortex EEG in rats. Am. J. Physiol. 289, R1083–R1089 (2005).

    CAS  Google Scholar 

  26. Huber, R. et al. Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity. Nature Neurosci. 9, 1169–1176 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Maquet, P. The role of sleep in learning and memory. Science 294, 1048–1052 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Drummond, S. P. A. et al. Sleep deprivation-induced reduction in cortical functional response to serial subtraction. Neuroreport 10, 3745–3748 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Mascetti, G. G., Rugger, M., Vallortigara, G. & Boddo, D. Monocular-unihemispheric sleep and visual discrimination learning in the domestic chick. Exp. Brain Res. 176, 70–84 (2007).

    Article  PubMed  Google Scholar 

  30. Frank, M. G., Issa, N. P. & Stryker, M. P. Sleep enhances plasticity in the developing visual cortex. Neuron 30, 275–287 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Marks, G. A., Shaffery, J. P., Oksenberg, A., Speciale, S. G. & Roffwarg, H. P. A functional role for REM sleep in brain maturation. Behav. Brain Res. 69, 1–11 (1995).

    Article  CAS  PubMed  Google Scholar 

  32. Rector, D. M., Topchiy, I. & Rojas, M. Local cortical column activity states and localized delta wave differences. Sleep 28, A26 (2005).

    Google Scholar 

  33. Obal, F. Jr & Krueger, J. M. Biochemical regulation of sleep. Front. Biosci. 8, 520–550 (2003).

    Article  Google Scholar 

  34. Borbély, A. A. & Tobler, I. Endogenous sleep-promoting substances and sleep regulation. Physiol. Rev. 69, 605–670 (1989).

    Article  PubMed  Google Scholar 

  35. Jouvet, M. Neuromediateurs et facteurs hypnogenes. Rev. Neurol. (Paris) 140, 389–400 (1984).

    CAS  Google Scholar 

  36. Krueger, J. M. & Obál, F. Jr. in Sleep and Breathing (eds Saunders, N. A. & Sullivan, C. E.) 79–112 (Dekker, Inc., New York, 1994).

    Google Scholar 

  37. Inoué, S. Biology of S leep Substances. (CRC, Boca Raton, 1989).

    Google Scholar 

  38. Basheer, R., Strecker, R. E., Thakkar, M. M. & McCarley, R. W. Adenosine and sleep-wake regulation. Prog. Neurobiol. 73, 379–396 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. De Sarro, G., Gareri, P., Sinopoli, V. A., David, E. & Rotiroti, D. Comparative, behavioural and electrocortical effects of tumor necrosis factor-α and interleukin-1 microinjected into the locus coeruleus of rat. Life Sci. 60, 555–564 (1997).

    Article  CAS  PubMed  Google Scholar 

  40. Manfridi, A. et al. 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, 1041–1049 (2003).

    Article  PubMed  Google Scholar 

  41. De, A., Churchill, L., Obal, F. Jr, Simasko, S. & Krueger, J. M. GHRH and IL1β increase cytoplasmic Ca2+ levels in cultured hypothalamic GABAergic neurons. Brain Res. 949, 209–212 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Yasuda, T., Yoshida, H., Garcia-Garcia, F., Kay, D. & Krueger, J. M. Interleukin-1β has a role in cerebral cortical state dependent electroencephalographic slow-wave activity. Sleep 28, 177–184 (2005).

    Article  PubMed  Google Scholar 

  43. Yoshida, H. et al. State-specific asymmetries in EEG slow wave activity induced by local application of TNFα. Brain Res. 1009, 129–136 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Szentirmai, E. et al. Growth hormone releasing hormone: cerebral cortical EEG actions and expression. Am. J. Physiol. 293, R922–R930 (2007).

    CAS  Google Scholar 

  45. Taishi, P. et al. TNFα siRNA reduces brain TNF and EEG delta wave activity in rats. Brain Res. 1156, 125–132 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Churchill, L. et al. Tumor necrosis factor α: activity dependent expression and promotion of cortical column sleep in rats. Neuroscience 156, 71–80 (2008).

    Article  CAS  PubMed  Google Scholar 

  47. Obal, F. Jr & Krueger, J. M. in The Physiological Nature of Sleep (eds Parmeggiani, P. L. & Velluti, R.) 23–44 (Imperial College Press, 2004).

    Google Scholar 

  48. Tabarean, I. V., Korn, H. & Bartfai, T. Interleukin-1β induces hyperpolarization and modulates synaptic inhibition in preoptic and anterior hypothalamic neurons. Neuroscience 4, 1685–1695 (2006).

    Article  CAS  Google Scholar 

  49. Alam, M. N. et al. Interleukin-1β modulates state-dependent discharge activity of preoptic area and basal forebrain neurons: role in sleep regulation. Eur. J. Neurosci. 20, 207–216 (2004).

    Article  PubMed  Google Scholar 

  50. Shibata, M. Hypothalamic neuronal responses to cytokines. Yale J. Biol. Med. 63, 147–156 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Schinder, A. F. & Poo, M.-M. The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci. 23, 639–645 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Houzen, H., Kikuchi, S., Kanno, M., Shinpo, K. & Tashiro, K. Tumor necrosis factor enhancement of transient outward potassium currents in cultured rat cortical neurons. J. Neurosci. Res. 50, 990–999 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Diem, R., Meyer, R., Weishaupt, J. H. & Bahr, M. Reduction of potassium currents in phosphatidylinositol 3-kinase-dependent AKT phosphorylation by tumor necrosis factor-α rescues axotomized retinal ganglion cells from retrograde cell death in vivo. J. Neurosci. 21, 2058–2066 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Koller, H., Allert, N., Oel, D., Stoll, G. & Siebler, M. TNF alpha induces a protein kinase C-dependent reduction in astroglial K+ conductance. Neuroreport 9, 1375–1378 (1998).

    Article  CAS  PubMed  Google Scholar 

  55. McLarnon, J. G. et al. Acute actions of tumor necrosis factor-α on intracellular Ca2+ and K+ currents in human microglia. Neuroscience 104, 1175–1184 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Kawada, H. et al. Tumor necrosis factor-α downregulates the voltage gated outward K+ current in cultured neonatal rat cardiomyocytes: a possible cause of electrical remodeling in diseased hearts. Circ. J. 70, 605–609 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Saper, C. B., Scammell, T. E. & Lu, J. Hypothalamic regulation of sleep and circadian rhythms. Nature 437, 1257–1263 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Yasuda, K. et al. Unilateral cortical application of interleukin-1β (IL1β) induces asymmetry in Fos- and IL1β-immunoreactivity: implication for sleep regulation. Brain Res. 1131, 44–59 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Churchill, L. et al. Unilateral cortical application of tumor necrosis factor α induces asymmetry in Fos- and interleukin-1β-immunoreactive cells within the corticothalamic projection. Brain Res. 1055, 15–24 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Krueger, J. M., Rector, D. M. & Churchill, L. Sleep and cytokines. Sleep Med. Clin. 2, 161–170 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  61. De, A., Fix, C., Hall, S., Churchill, L. & Krueger, J. M. Growth hormone releasing hormone receptive immuno-reactive cells increase in the barrel field in response to whisker deflection in rats. Sleep 29, A9 (2006).

    Google Scholar 

  62. De, A., Krueger, J. M. & Simasko, S. M. Glutamate induces expression and release of tumor necrosis factor-α in cultured hypothalamic cells. Brain Res. 1053, 54–61 (2005).

    Article  CAS  PubMed  Google Scholar 

  63. Gerashchenko, D. et al. Identification of a population of sleep-active cerebral cortex neurons. Proc. Natl Acad. Sci. USA 105, 10227–10232 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kapas, L., Fang, J. & Krueger, J. M. Inhibition of nitric oxide synthesis inhibits rat sleep. Brain Res. 664, 189–196 (1994).

    Article  CAS  PubMed  Google Scholar 

  65. Landolt, H. P., Dijk, D. J., Gaus, S. E. & Borbely, A. A. Caffeine reduces low-frequency delta activity in the human sleep EEG. Neuropsychopharmacology 12, 229–238 (1995).

    Article  CAS  PubMed  Google Scholar 

  66. Farber, K. & Kettenmann, H. Purinergic signaling and microglia. Pflugers Arch. 452, 615–621 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Burnstock, G. Physiology and pathology of purinergic neurotransmission. Physiol. Rev. 87, 659–797 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Hide, I. et al. Extracellular ATP triggers tumor necrosis factor-α release from rat microglia. J. Neurochem. 75, 965–972 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Suzuki, T. et al. Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. J. Neurosci. 24, 1–7 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bianco, F. et al. Astrocyte-derived ATP induces vesicle shedding and IL-1β release from microglia. J. Immunol. 174, 7268–7277 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Williams, J. A., Sathyanarayanan, S., Hendricks, J. C. & Sehgal, A. Interaction between sleep and the immune response in Drosophila: a role for the NFκB Relish. Sleep 30, 389–400 (2007).

    Article  PubMed  Google Scholar 

  72. Jajoo, S., Mukherjea, D., Pingle, S., Sekino, Y. & Ramkumar, V. Induction of adenosine A1 receptor expression by pertussis toxin via an adenosine 5′-diphosphate ribosylation-independent pathway. J. Pharmacol. Exp. Ther. 317, 1–10 (2006).

    Article  CAS  PubMed  Google Scholar 

  73. Yu, Z. et al. Tumor necrosis factor α increases neuronal vulnerability to excitotoxic necrosis by inducing expression of the AMPA–glutamate receptor subunit GluR1 via an acid sphingomyelinase- and NF-κB-dependent mechanism. Neurobiol. Dis. 11, 199–213 (2002).

    Article  CAS  PubMed  Google Scholar 

  74. Kaneko, M., Stellwagen, D., Malenka, R. C. & Stryker, M. P. Tumor necrosis factor-α mediates one component of competitive, experience-dependent plasticity in developing visual cortex. Neuron 58, 673–680 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Schei, J. L., Foust, A. J., Rojas, M. J., Navas, J. A. & Rector, D. M. Evoked optical responses differ between quiet sleep stages. Sleep 31, A7 (2008).

    Google Scholar 

  76. Taishi, P., Churchill, L., De, A., Obal, F. & Krueger, J. M. Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo. Brain Res. 1226, 89–98 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Roy, S., Krueger, J. M., Rector, D. M. & Wan, Y. Network models for activity-dependent sleep regulation. J. Theor. Biol. 253, 462–468 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Mirollo, R. E. & Strogatz, S. H. Synchronization of pulse-coupled biological oscillators. SIAM J. Appl. Math. 50, 1645–1662 (1990).

    Article  Google Scholar 

  79. Asavathiratham, C., Roy S., Lesieutre, B. C. & Verghese, G. C. The influence model. IEEE Control Syst. Mag. NY 21, 52–64 (2001).

    Article  Google Scholar 

  80. Wilson, H. R. & Cowan, J. D. Excitatory and inhibitory interactions in localized populations of model neurons. Biophys. J. 12, 1–24 (1974).

    Article  Google Scholar 

  81. Kavanau, J. L. Sleep and dynamic stabilization of neural circuitry: a review and synthesis. Behav. Brain Res. 63, 111–126 (1994). This is a scholarly development of the idea that experience-driven changes in neural connectivity lead to dysfunction unless there is a mechanism in place to temper such activity. The author posits that the intrinsic electrical activity of the brain stabilizes the activity-altered circuits and that this is a function of sleep.

    Article  CAS  PubMed  Google Scholar 

  82. Siegel, J. M. Clues to the functions of mammalian sleep. Nature 437, 1264–1271 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Tononi, G. & Cirelli, C. Sleep function and synaptic homeostasis. Sleep Med. Rev. 10, 49–62 (2006).

    Article  PubMed  Google Scholar 

  84. Crick, F. & Mitchinson, G. The function of dream sleep. Nature 304, 111–114 (1983).

    Article  CAS  PubMed  Google Scholar 

  85. Abbott, L. F. & Nelson, S. B. Synaptic plasticity: taming the beast. Nature Neurosci. 3, 1178–1183 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Stellwagen, D. & Malenka, R. C. Synaptic scaling mediated by glial TNF-α. Nature 440, 1054–1059 (2006). The authors show that TNF, an SRS, is involved in synaptic scaling. The implications for sleep are that sleep-regulatory mechanisms cannot be separated from a sleep-connectivity stabilization function.

    Article  CAS  PubMed  Google Scholar 

  87. Nofzinger, E. A. et al. Regional cerebral metabolic correlates of WASO during NREMS sleep in insomnia. J. Clin. Sleep Med. 2, 316–322 (2006).

    PubMed  Google Scholar 

  88. Edelman, G. H. Neural Darwinsim (Basic Books, New York, 1987).

    Google Scholar 

  89. Panksepp, J. Affective Neuroscience (Oxford Univ. Press, New York, 1998).

    Google Scholar 

  90. Brandt, J. A. et al. Sleep-deprivation but not a whisker trim increases nerve growth factor within barrel cortical neurons. Brain Res. 898, 105–112 (2001). This report demonstrates that the interaction of afferent activity and sleep alters the expression of an SRS in neurons. As such it provides evidence for a mechanism by which local sleep is tied to prior activity.

    Article  CAS  PubMed  Google Scholar 

  91. Krueger, J. M. Obal, F. Jr, Kapas, L. & Fang, J. Brain organization and sleep function. Behav. Brain Res. 69, 177−185 (1995).

  92. De, A., Krueger, J. M. & Simasko, S. M. Tumor necrosis factor α increases cytosolic calcium response AMPA and KCl in primary cultures of rat hippocampal neurons. Brain Res. 981, 133–142 (2003).

    Article  CAS  PubMed  Google Scholar 

  93. Beattie, E. C. et al. Control of synaptic strength by glial TNFα. Science 295, 2282–2285 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Bazhenov, M., Timofeev, I., Steriade, M. & Sejnowski, T. J. Model of thalamocortical slow-wave sleep oscillations and transitions to activated states. J. Neurosci. 22, 8691–8704 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Malinow, R. & Malenka, R. C. AMPA receptor trafficking and synaptic plasticity. Ann. Rev. Neurosci. 25, 103–126 (2002).

    Article  CAS  PubMed  Google Scholar 

  96. Lai, A. Y., Swayze, R. D., El-Husseini, A. & Song, C. Interleukin-1β modulates AMPA receptor expression and phosphorylation in hippocampal neurons. J. Neuroimmunol. 175, 97–106 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Czarnecki, A., Birtoli, B. & Ulrich, D. Cellular mechanisms of burst-firing mediated long-term depression in rat neocortical pyramidal cells. J. Physiol. 578, 471–479 (2007).

    Article  CAS  PubMed  Google Scholar 

  98. Takahashi, S. & Krueger, J. M. Inhibition of tumor necrosis factor prevents warming-induced sleep responses in rabbits. Am. J. Physiol. 272, R1325–R1329 (1997).

    CAS  PubMed  Google Scholar 

  99. Majde, J. A. & Krueger, J. M. Links between the innate immune system and sleep. J. Allergy Clin. Immunol. 116, 1188–1198 (2005).

    Article  CAS  PubMed  Google Scholar 

  100. Ferrari, D. et al. The P2X7 receptor: a key player in IL-1 processing and release. J. Immunol. 176, 3877–3883 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the W.M. Keck Foundation, the US National Institutes of Health (grant numbers NS 25378, NS 31453 and MH 71830), the US Army Research Development and Material Command, the National Science Foundation, and the National Aeronautics and Space Administration.

Author information

Authors and Affiliations

  1. Department of VCAPP, College of Veterinary Medicine, Washington State University, PO BOX 646520, Pullman, 99164-6520, Washington, USA

    James M. Krueger

  2. Sleep and Performance Research Center and Programs in Neuroscience, Washington State University, Pullman and Spokane, 99164-6520, Washington, USA

    James M. Krueger, David M. Rector, Hans P. A. Van Dongen, Gregory Belenky & Jaak Panksepp

  3. Electrical Engineering, Washington State University, Pullman and Spokane, 99164-6520, Washington, USA

    Sandip Roy

Authors
  1. James M. Krueger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David M. Rector
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandip Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hans P. A. Van Dongen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gregory Belenky
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jaak Panksepp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James M. Krueger.

Related links

Related links

FURTHER INFORMATION

James Krueger's homepage

Glossary

Cortical columns

Collections of highly interconnected neurons that often focus on particular tasks. Columns are layered structures, and the individual layers are concerned with different functions, such as the receipt of afferent input and producing an output. There is more intercellular connectivity within columns than between columns. This makes each column a functional unit. In humans, each column contains 1,000–10,000 cells and there are ∼100,000 cortical columns.

Parasomnias

States in which behavioural or physical phenomena that are characteristic of waking occur while parts of the body seem to be asleep. Sleep walking is a well-known example of a parasomnia.

Non-rapid-eye-movement sleep

(NREMS). A type of sleep characterized by high-amplitude (up to 500 μV) electroencephalographic slow waves (delta waves). In humans it is often divided into four stages, the first two of which are characterized less by delta waves than by a transition from fast to slower electroencephalographic activity. In intermediate stages of NREMS, thalamic cells produce 8–12 Hz bursts known as spindles, which also characterize lighter stages of NREMS.

Delta-wave power

The calculated power (in μV2) of delta waves, obtained from fast fourier transformations of the EEG. Delta waves are from 0.5–3.5 Hz. Delta-wave power is higher during sleep after sleep deprivation and is considered an indicator of NREMS intensity. Delta waves are generated by the synchronous and cyclical switching of cortical cells between a hyperpolarized and a depolarized state. Although this rhythm is present in isolated cortical slices, similar rhythms occur in the thalamus and might drive the cortical cells into alternating hyperpolarized and depolarized states.

Rapid-eye-movement sleep

A state characterized by a relatively fast waveform EEG and a flat electromyogram in postural muscles. This state is also well known for the vivid dreams that can be remembered.

Evoked response potentials

The field potentials measured from electrodes on the surface of the cerebral cortex or scalp that occur in response to sensory afferent stimulation. Synchronous synaptic activation of many cells in a cortical column generates an electrical potential gradient that can be detected by the electrodes. By using multiple electrodes and/or discrete sensory stimuli, these potentials can be localized to individual cortical columns.

Clock mechanisms of the suprachiasmatic nuclei

In mammals the suprachiasmatic nuclei of the hypothalamus house the cellular and molecular mechanisms that are responsible for circadian rhythms. If the suprachiasmatic nuclei are lesioned, circadian rhythms that are normally entrained by light are lost. In the absence of light–dark cues, normal animals exhibit rhythms that approximate 24 hours through the actions of the free-running molecular oscillators in the suprachiasmatic cells.

Sleep-active neurons

Neurons with activity that increases during sleep or just before sleep onset.

Wake-active neurons

Neurons with activity that increases during wakefulness or just before wakefulness onset.

Hebbian plasticity

The type of rapid (on the scale of minutes to hours) changes in neuronal connectivity that are associated with use of the network of which the neurons are a part. The term is derived from the work of Donald Hebb, a Canadian psychologist who first posited, in 1949, that neurons that fire together tend to wire together.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Krueger, J., Rector, D., Roy, S. et al. Sleep as a fundamental property of neuronal assemblies. Nat Rev Neurosci 9, 910–919 (2008). https://doi.org/10.1038/nrn2521

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2521

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing