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Sleep-active cells in the cerebral cortex and their role in slow-wave activity

Sleep and Biological Rhythms volume 9, pages 71–77 (2011)Cite this article

Abstract

We recently identified neurons in the cerebral cortex that become activated during sleep episodes with high slow-wave activity (SWA). The distinctive properties of these neurons are the ability to produce nitric oxide and their long-range projections within the cortex. In this review, we discuss how these characteristics of sleep-active cells could be relevant to SWA production in the cortex. We also discuss possible models of the role of nNOS cells in SWA production.

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References

  1. Achermann P, Borbely AA. Dynamics of EEG slow wave activity during physiological sleep and after administration of benzodiazepine hypnotics. Hum. Neurobiol. 1987; 6: 203–10.

    CAS  PubMed  Google Scholar 

  2. Borbély AA, Achermann P. Sleep homeostasis and models of sleep regulation. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. W.B. Saunders Co.: Philadelphia, 2000; 377–90.

    Google Scholar 

  3. Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Med. Rev. 2006; 10: 49–62.

    Article  PubMed  Google Scholar 

  4. Walsh JK, Randazzo AC, Stone K et al. Tiagabine is associated with sustained attention during sleep restriction: evidence for the value of slow-wave sleep enhancement? Sleep 2006; 29: 433–43.

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Birtoli B, Ulrich D. Firing mode-dependent synaptic plasticity in rat neocortical pyramidal neurons. J. Neurosci. 2004; 24 (21): 4935–40.

    Article  CAS  PubMed  Google Scholar 

  7. Benington JH, Heller HC. Restoration of brain energy metabolism as the function of sleep. Prog. Neurobiol. 1995; 45: 347–60.

    Article  CAS  PubMed  Google Scholar 

  8. Dhand R, Sohal H. Good sleep, bad sleep! The role of daytime naps in healthy adults. Curr. Opin. Pulm. Med. 2006; 12: 379–82.

    Article  PubMed  Google Scholar 

  9. Tasali E, Leproult R, Ehrmann DA, Van Cauter E. Slowwave sleep and the risk of type 2 diabetes in humans. Proc. Natl. Acad. Sci. U. S. A. 2008; 105 (3): 1044–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Llinas R, Urbano FJ, Leznik E, Ramirez RR, van Marle HJ. Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect. Trends. Neurosci. 2005; 28: 325–33.

    Article  CAS  PubMed  Google Scholar 

  11. Steriade M, Amzica F. Coalescence of sleep rhythms and their chronology in corticothalamic networks. Sleep Res. Online. 1998; 1 (1): 1–10.

    CAS  PubMed  Google Scholar 

  12. Destexhe A, Contreras D. Neuronal computations with stochastic network states. Science 2006; 314 (5796): 85–90.

    Article  CAS  PubMed  Google Scholar 

  13. Steriade M, Dossi RC, Nunez A. 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. 1991; 11 (10): 3200–17.

    CAS  PubMed  Google Scholar 

  14. Rey M, Bastuji H, Garcia-Larrea L, Guillemant P, Mauguiere F, Magnin M. Human thalamic and cortical activities assessed by dimension of activation and spectral edge frequency during sleep wake cycles. Sleep 2007; 30 907–12.

    PubMed  PubMed Central  Google Scholar 

  15. Magnin M, Rey M, Bastuji H, Guillemant P, Mauguiere F, Garcia-Larrea L. Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans. Proc. Natl. Acad. Sci. U. S. A. 2010; 107 (8): 3829–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Velly LJ, Rey MF, Bruder NJ et al. Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia. Anesthesiology 2007; 107: 202–12.

    Article  CAS  PubMed  Google Scholar 

  17. Steriade M, Nunez A, Amzica F. Intracellular analysis of relations between the slow (?1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. J. Neurosci. 1993; 13 (8): 3266–83.

    CAS  PubMed  Google Scholar 

  18. Hoffman GE, Lyo D. Anatomical markers of activity in neuroendocrine systems: are we all “fosed out”? J. Neuroendocrinol. 2002; 14: 259–68.

    Article  CAS  PubMed  Google Scholar 

  19. Gerashchenko D, Wisor JP, Burns D et al. Identification of a population of sleep-active cerebral cortex neurons. Proc. Natl. Acad. Sci. U. S. A. 2008; 105 (29): 10227–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pasumarthi R, Gershchenko D, Kilduff TS. Further characterization of sleep-active nNOS neurons in the mouse brain. Neuroscience 2010; 169 (1): 149–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tobler I, Jaggi K. Sleep and EEG spectra in the Syrian hamster (Mesocricetus auratus) under baseline conditions and following sleep deprivation. J. Comp. Physiol. [A] 1987; 161: 449–59.

    Article  CAS  Google Scholar 

  22. Ayers NA, Kapas L, Krueger JM. Circadian variation of nitric oxide synthase activity and cytosolic protein levels in rat brain. Brain Res. 1996; 707: 127–30.

    Article  CAS  PubMed  Google Scholar 

  23. Hilbig H, Punkt K. 24-hour rhythmicity of NADPHdiaphorase activity in the neuropil of rat visual cortex. Brain Res. Bull. 1997; 43: 337–40.

    Article  CAS  PubMed  Google Scholar 

  24. Clement P, Gharib A, Cespuglio R, Sarda N. Changes in the sleep-wake cycle architecture and cortical nitric oxide release during ageing in the rat. Neuroscience 2003; 116 (3): 863–70.

    Article  CAS  PubMed  Google Scholar 

  25. Clement P, Sarda N, Cespuglio R, Gharib A. Changes occurring in cortical NO release and brain NO-synthases during a paradoxical sleep deprivation and subsequent recovery in the rat. J. Neurochem. 2004; 90 (4): 848–56.

    Article  CAS  PubMed  Google Scholar 

  26. Cespuglio R, Debilly G, Burlet S. Cortical and pontine variations occurring in the voltammetric no signal throughout the sleep-wake cycle in the rat. Arch. Ital. Biol. 2004; 142 (4): 551–6.

    CAS  PubMed  Google Scholar 

  27. Marino J, Cudeiro J. Nitric oxide-mediated cortical activation: a diffuse wake-up system. J. Neurosci. 2003; 23 (10): 4299–307.

    CAS  PubMed  Google Scholar 

  28. Iadecola C. Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link? Trends. Neurosci. 1993; 16: 206–14.

    Article  CAS  PubMed  Google Scholar 

  29. Estrada C, DeFelipe J. Nitric oxide-producing neurons in the neocortex: morphological and functional relationship with intraparenchymal microvasculature. Cereb. Cortex 1998; 8: 193–203.

    Article  CAS  PubMed  Google Scholar 

  30. Kitaura H, Uozumi N, Tohmi M et al. Roles of nitric oxide as a vasodilator in neurovascular coupling of mouse somatosensory cortex. Neurosci. Res. 2007; 59 160–71.

    Article  CAS  PubMed  Google Scholar 

  31. Kara P, Friedlander MJ. Dynamic modulation of cerebral cortex synaptic function by nitric oxide. Prog. Brain Res. 1998; 118: 183–98.

    Article  CAS  PubMed  Google Scholar 

  32. Wakatsuki H, Gomi H, Kudoh M et al. Layer-specific NO dependence of long-term potentiation and biased NO release in layer V in the rat auditory cortex. J. Physiol. 1998; 513 (Pt 1): 71–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. O’Donnell P, Grace AA. Cortical afferents modulate striatal gap junction permeability via nitric oxide. Neuroscience 1997; 76 (1): 1–5.

    Article  PubMed  Google Scholar 

  34. Strata F, Atzori M, Molnar M, Ugolini G, Berretta N, Cherubini E. Nitric oxide sensitive depolarizationinduced hyperpolarization: a possible role for gap junctions during development. Eur. J. Neurosci. 1998; 10 (1): 397–403.

    Article  CAS  PubMed  Google Scholar 

  35. Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends. Neurosci. 1991; 14 (2): 60–7.

    Article  CAS  PubMed  Google Scholar 

  36. Stamler JS, Simon DI, Osborne JA et al. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc. Natl. Acad. Sci. U. S. A. 1992; 89 (1): 444–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Schuman EM, Madison DV. Nitric oxide and synaptic function. Annu. Rev. Neurosci. 1994; 17: 153–83.

    Article  CAS  PubMed  Google Scholar 

  38. Gally JA, Montague PR, Reeke GN Jr, Edelman GM. The NO hypothesis: possible effects of a short-lived, rapidly diffusible signal in the development and function of the nervous system. Proc. Natl. Acad. Sci. U. S. A. 1990; 87 (9): 3547–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jansson A, Mazel T, Andbjer B et al. Effects of nitric oxide inhibition on the spread of biotinylated dextran and on extracellular space parameters in the neostriatum of the male rat. Neuroscience 1999; 91 (1): 69–80.

    Article  CAS  PubMed  Google Scholar 

  40. Gelperin A. Nitric oxide mediates network oscillations of olfactory interneurons in a terrestrial mollusc. Nature 1994; 369 (6475): 61–3.

    Article  CAS  PubMed  Google Scholar 

  41. Garthwaite J, Boulton CL. Nitric oxide signaling in the central nervous system. Annu. Rev. Physiol. 1995; 57 683–706.

    Article  CAS  PubMed  Google Scholar 

  42. Chen L, Majde JA, Krueger JM. Spontaneous sleep in mice with targeted disruptions of neuronal or inducible nitric oxide synthase genes. Brain Res. 2003; 973 (2): 214–22.

    Article  CAS  PubMed  Google Scholar 

  43. Aeschbach D, Cajochen C, Landolt H, Borbely AA. Homeostatic sleep regulation in habitual short sleepers and long sleepers. Am. J. Physiol. 1996; 270 (1 Pt 2): R41–R53.

    CAS  PubMed  Google Scholar 

  44. Chen L, Taishi P, Majde JA, Peterfi Z, Obal F Jr, Krueger JM. The role of nitric oxide synthases in the sleep responses to tumor necrosis factor-alpha. Brain Behav. Immun. 2004; 18 (4): 390–8.

    Article  CAS  PubMed  Google Scholar 

  45. Obal FJ, Krueger JM. Biochemical regulation of nonrapid- eye-movement sleep. Front. Biosci. 2003; 8: D520–D550.

    Article  CAS  PubMed  Google Scholar 

  46. Takahashi S, Kapas L, Krueger JM. A tumor necrosis factor (TNF) receptor fragment attenuates TNF-alphaand muramyl dipeptide-induced sleep and fever in rabbits. J. Sleep Res. 1996; 5 (2): 106–14.

    Article  CAS  PubMed  Google Scholar 

  47. Takahashi S, Kapas L, Seyer JM, Wang Y, Krueger JM. Inhibition of tumor necrosis factor attenuates physiological sleep in rabbits. Neuroreport 1996; 7 (2): 642–6.

    Article  CAS  PubMed  Google Scholar 

  48. Takahashi S, Krueger JM. Inhibition of tumor necrosis factor prevents warming-induced sleep responses in rabbits. Am. J. Physiol. 1997; 272 (4 Pt 2): R1325–R1329.

    CAS  PubMed  Google Scholar 

  49. Murphy M, Riedner BA, Huber R, Massimini M, Ferrarelli F, Tononi G. Source modeling sleep slow waves. Proc. Natl. Acad. Sci. U. S. A. 2009; 106 (5): 1608–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mohajerani MH, McVea DA, Fingas M, Murphy TH. Mirrored bilateral slow-wave cortical activity within local circuits revealed by fast bihemispheric voltage-sensitive dye imaging in anesthetized and awake mice. J. Neurosci. 2010; 30 (10): 3745–51.

    Article  CAS  PubMed  Google Scholar 

  51. DeFelipe J, Farinas I. The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. Prog. Neurobiol. 1992; 39 (6): 563–607.

    Article  CAS  PubMed  Google Scholar 

  52. McDonald CT, Burkhalter A. Organization of long-range inhibitory connections with rat visual cortex. J. Neurosci. 1993; 13 (2): 768–81.

    CAS  PubMed  Google Scholar 

  53. Fabri M, Manzoni T. Glutamate decarboxylase immunoreactivity in corticocortical projecting neurons of rat somatic sensory cortex. Neuroscience 1996; 72 (2): 435–48.

    Article  CAS  PubMed  Google Scholar 

  54. Aroniadou-Anderjaska V, Keller A. Intrinsic inhibitory pathways in mouse barrel cortex. Neuroreport 1996; 7 (14): 2363–8.

    Article  CAS  PubMed  Google Scholar 

  55. Albus K, Wahle P. The topography of tangential inhibitory connections in the postnatally developing and mature striate cortex of the cat. Eur. J. Neurosci. 1994; 6 (5): 779–92.

    Article  CAS  PubMed  Google Scholar 

  56. Peters A, Payne BR, Josephson K. Transcallosal nonpyramidal cell projections from visual cortex in the cat. J. Comp. Neurol. 1990; 302 (1): 124–42.

    Article  CAS  PubMed  Google Scholar 

  57. Gonchar YA, Johnson PB, Weinberg RJ. GABAimmunopositive neurons in rat neocortex with contralateral projections to S-I. Brain Res. 1995; 697 (1–2): 27–34.

    Article  CAS  PubMed  Google Scholar 

  58. Kimura F, Baughman RW. GABAergic transcallosal neurons in developing rat neocortex. Eur. J. Neurosci. 1997; 9: 1137–43.

    Article  CAS  PubMed  Google Scholar 

  59. Tomioka R, Okamoto K, Furuta T et al. Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex. Eur. J. Neurosci. 2005; 21 (6): 1587–600.

    Article  PubMed  Google Scholar 

  60. Higo S, Udaka N, Tamamaki N. Long-range GABAergic projection neurons in the cat neocortex. J. Comp. Neurol. 2007; 503: 421–31.

    Article  PubMed  Google Scholar 

  61. Tomioka R, Rockland KS. Long-distance corticocortical GABAergic neurons in the adult monkey white and gray matter. J. Comp. Neurol. 2007; 505: 526–38.

    Article  PubMed  Google Scholar 

  62. Volgushev M, Chauvette S, Mukovski M, Timofeev I. Precise long-range synchronization of activity and silence in neocortical neurons during slow-wave oscillations [corrected]. J. Neurosci. 2006; 26 (21): 5665–72.

    Article  CAS  PubMed  Google Scholar 

  63. Chauvette S, Volgushev M, Timofeev I. Origin of active states in local neocortical networks during slow sleep oscillation. Cereb. Cortex 2010; 20 (11): 2660–74.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Jones BE. Activity, modulation and role of basal forebrain cholinergic neurons innervating the cerebral cortex. Prog. Brain Res. 2004; 145: 157–69.

    Article  CAS  PubMed  Google Scholar 

  65. McCarley RW. Neurobiology of REM and NREM sleep. Sleep Med. 2007; 8 (4): 302–30.

    Article  PubMed  Google Scholar 

  66. Fujitani Y, Urade Y, Hayaishi O. [Sleep-promoting substances]. Nippon Ronen Igakkai Zasshi 1998; 35 (11): 811–16.

    Article  CAS  PubMed  Google Scholar 

  67. Kilduff TS, Cauli B, Gershchenko D. Activation of cortical interneurons during sleep: an anatomical link to sleep homeostasis? Trends. Neurosci. 2010 (in press).

    Google Scholar 

  68. Llinas RR, Steriade M. Bursting of thalamic neurons and states of vigilance. J. Neurophysiol. 2006; 95 (6): 3297–308.

    Article  PubMed  Google Scholar 

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Author notes

  1. Dmitry Gerashchenko

    Present address: Harvard Medical School/VA Medical Center, 1400 VFW Parkway, West Roxbury, MA, 02132, USA

  2. Jonathan P. Wisor

    Present address: Washington State University, 320K Health Sciences Bldg, Spokane, WA, 99210, USA

Authors and Affiliations

  1. Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California, USA

    Dmitry Gerashchenko, Jonathan P. Wisor & Thomas S. Kilduff

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  1. Dmitry Gerashchenko
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  2. Jonathan P. Wisor
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  3. Thomas S. Kilduff
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Correspondence to Dmitry Gerashchenko.

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Gerashchenko, D., Wisor, J.P. & Kilduff, T.S. Sleep-active cells in the cerebral cortex and their role in slow-wave activity. Sleep Biol. Rhythms 9 (Suppl 1), 71–77 (2011). https://doi.org/10.1111/j.1479-8425.2010.00461.x

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