Sleep and Synaptic Homeostasis

  • Vladyslav V. VyazovskiyEmail author
  • Ugo Faraguna
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 25)


In the last decades a substantial knowledge about sleep mechanisms has been accumulated. However, the function of sleep still remains elusive. The difficulty with unraveling sleep’s function may arise from the lack of understanding of how the multitude of processes associated with waking and sleep—from gene expression and single neuron activity to the whole brain dynamics and behavior—functionally and mechanistically relate to each other. Therefore, novel conceptual frameworks, which integrate and take into account the variety of phenomena occurring during waking and sleep at different levels, will likely lead to advances in our understanding of the function of sleep, above and beyond what merely descriptive or correlative approaches can provide. One such framework, the synaptic homeostasis hypothesis, focuses on wake- and sleep-dependent changes in synaptic strength. The core claim of this hypothesis is that learning and experience during wakefulness are associated with a net increase in synaptic strength. In turn, the proposed function of sleep is to provide synaptic renormalization, which has important implications with respect to energy needs, intracranial space, metabolic supplies, and, importantly, enables further plastic changes. In this article we review the empirical evidence for this hypothesis, which was obtained at several levels—from gene expression and cellular excitability to structural synaptic modifications and behavioral outcomes. We conclude that although the mechanisms behind the proposed role of sleep in synaptic homeostasis are undoubtedly complex, this conceptual framework offers a unique opportunity to provide mechanistic and functional explanation for many previously disparate observations, and define future research strategies.


Homeostasis Slow waves Slow wave activity Synaptic downscaling Pruning 



We would like to thank Drs Giulio Tononi and Chiara Cirelli for their valuable comments on the manuscript.


  1. Abbott LF, Nelson SB (2000) Synaptic plasticity: taming the beast. Nat Neurosci 3(Suppl):1178–1183PubMedGoogle Scholar
  2. Abel T, Havekes R, Saletin JM, Walker MP (2013) Sleep, plasticity and memory from molecules to whole-brain networks. Curr Biol 23:R774–R788PubMedCentralPubMedGoogle Scholar
  3. Achermann P, Finelli LA, Borbely AA (2001) Unihemispheric enhancement of delta power in human frontal sleep EEG by prolonged wakefulness. Brain Res 913:220–223PubMedGoogle Scholar
  4. Alam MA, Kumar S, McGinty D, Alam MN, Szymusiak R (2014) Neuronal activity in the preoptic hypothalamus during sleep deprivation and recovery sleep. J Neurophysiol 111:287–299PubMedCentralPubMedGoogle Scholar
  5. Alhaider IA, Aleisa AM, Tran TT, Alkadhi KA (2011) Sleep deprivation prevents stimulation-induced increases of levels of P-CREB and BDNF: protection by caffeine. Mol Cell Neurosci 46:742–751PubMedGoogle Scholar
  6. Anderson C, Horne JA (2003) Prefrontal cortex: links between low frequency delta EEG in sleep and neuropsychological performance in healthy, older people. Psychophysiology 40:349–357PubMedGoogle Scholar
  7. Appelbaum L, Wang G, Yokogawa T, Skariah GM, Smith SJ, Mourrain P, Mignot E (2010) Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron 68:87–98PubMedCentralPubMedGoogle Scholar
  8. Bailey CH, Kandel ER (2008) Synaptic remodeling, synaptic growth and the storage of long-term memory in Aplysia. Prog Brain Res 169:179–198PubMedGoogle Scholar
  9. Beltramo R, D’Urso G, Dal Maschio M, Farisello P, Bovetti S, Clovis Y, Lassi G, Tucci V, De Pietri Tonelli D, Fellin T (2013) Layer-specific excitatory circuits differentially control recurrent network dynamics in the neocortex. Nat Neurosci 16:227–234PubMedGoogle Scholar
  10. Bhakar AL, Dolen G, Bear MF (2012) The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci 35:417–443PubMedCentralPubMedGoogle Scholar
  11. Borbely AA (1982) A two process model of sleep regulation. Hum Neurobiol 1:195–204PubMedGoogle Scholar
  12. Borbély AA, Achermann P (2005) Sleep homeostasis and models of sleep regulation. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. W. B. Saunders, Philadelphia, pp 405–417Google Scholar
  13. Borbely AA, Tobler I, Hanagasioglu M (1984) Effect of sleep deprivation on sleep and EEG power spectra in the rat. Behav Brain Res 14:171–182PubMedGoogle Scholar
  14. Borbely AA, Tononi G (1998) The quest for the essence of sleep. Daedalus 127:167–196Google Scholar
  15. Braunewell KH, Manahan-Vaughan D (2001) Long-term depression: a cellular basis for learning? Rev Neurosci 12:121–140PubMedGoogle Scholar
  16. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW (2012) Control of sleep and wakefulness. Physiol Rev 92:1087–1187PubMedCentralPubMedGoogle Scholar
  17. Bushey D, Tononi G, Cirelli C (2011) Sleep and synaptic homeostasis: structural evidence in Drosophila. Science 332:1576–1581PubMedCentralPubMedGoogle Scholar
  18. Buzsaki G, Anastassiou CA, Koch C (2012) The origin of extracellular fields and currents—EEG, ECoG, LFP and spikes. Nat Rev Neurosci 13:407–420PubMedGoogle Scholar
  19. Cajochen C, Foy R, Dijk DJ (1999) Frontal predominance of a relative increase in sleep delta and theta EEG activity after sleep loss in humans. Sleep Res Online 2:65–69PubMedGoogle Scholar
  20. Campbell IG, Guinan MJ, Horowitz JM (2002) Sleep deprivation impairs long-term potentiation in rat hippocampal slices. J Neurophysiol 88:1073–1076PubMedGoogle Scholar
  21. Caporale N, Dan Y (2008) Spike timing-dependent plasticity: a Hebbian learning rule. Annu Rev Neurosci 31:25–46PubMedGoogle Scholar
  22. Castro CA, Silbert LH, McNaughton BL, Barnes CA (1989) Recovery of spatial learning deficits after decay of electrically induced synaptic enhancement in the hippocampus. Nature 342:545–548PubMedGoogle Scholar
  23. Chauvette S, Seigneur J, Timofeev I (2012) Sleep oscillations in the thalamocortical system induce long-term neuronal plasticity. Neuron 75:1105–1113PubMedCentralPubMedGoogle Scholar
  24. Chauvette S, Volgushev M, Timofeev I (2010) Origin of active states in local neocortical networks during slow sleep oscillation. Cereb Cortex 20:2660–2674PubMedCentralPubMedGoogle Scholar
  25. Churchill L, Rector DM, Yasuda K, Fix C, Rojas MJ, Yasuda T, Krueger JM (2008) Tumor necrosis factor alpha: activity dependent expression and promotion of cortical column sleep in rats. Neuroscience 156:71–80PubMedCentralPubMedGoogle Scholar
  26. Churchill L, Taishi P, Wang M, Brandt J, Cearley C, Rehman A, Krueger JM (2006) Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1beta or tumor necrosis factor alpha. Brain Res 1120:64–73PubMedGoogle Scholar
  27. Cirelli C (2002) How sleep deprivation affects gene expression in the brain: a review of recent findings. J Appl Physiol 92:394–400PubMedGoogle Scholar
  28. Cirelli C, Faraguna U, Tononi G (2006) Changes in brain gene expression after long-term sleep deprivation. J Neurochem 98:1632–1645PubMedGoogle Scholar
  29. Cirelli C, Tononi G (2000a) Differential expression of plasticity-related genes in waking and sleep and their regulation by the noradrenergic system. J Neurosci 20:9187–9194PubMedGoogle Scholar
  30. Cirelli C, Tononi G (2000b) Gene expression in the brain across the sleep–waking cycle. Brain Res 885:303–321PubMedGoogle Scholar
  31. Cirelli C, Tononi G (2008) Is sleep essential? PLoS Biol 6:e216PubMedCentralPubMedGoogle Scholar
  32. Crunelli V, Hughes SW (2009) The slow (<1 Hz) rhythm of non-REM sleep: a dialogue between three cardinal oscillators. Nat Neurosci 13:9–17PubMedCentralPubMedGoogle Scholar
  33. Curcio G, Ferrara M, De Gennaro L (2006) Sleep loss, learning capacity and academic performance. Sleep Med Rev 10:323–337PubMedGoogle Scholar
  34. Daan S, Beersma DG, Borbely AA (1984) Timing of human sleep: recovery process gated by a circadian pacemaker. Am J Physiol 246:R161–R183PubMedGoogle Scholar
  35. David F, Schmiedt JT, Taylor HL, Orban G, Di Giovanni G, Uebele VN, Renger JJ, Lambert RC, Leresche N, Crunelli V (2013) Essential thalamic contribution to slow waves of natural sleep. J Neurosci 33:19599–19610PubMedCentralPubMedGoogle Scholar
  36. Deboer T (2013) Behavioral and electrophysiological correlates of sleep and sleep homeostasis. Curr Top Behav Neurosci. doi: 10.1007/7854_2013_248
  37. Destexhe A, Contreras D, Steriade M (1999) Spatiotemporal analysis of local field potentials and unit discharges in cat cerebral cortex during natural wake and sleep states. J Neurosci 19:4595–4608PubMedGoogle Scholar
  38. Diekelmann S, Born J (2010) The memory function of sleep. Nat Rev Neurosci 11:114–126PubMedGoogle Scholar
  39. Donlea JM, Ramanan N, Shaw PJ (2009) Use-dependent plasticity in clock neurons regulates sleep need in Drosophila. Science 324:105–108PubMedCentralPubMedGoogle Scholar
  40. Doyere V, Srebro B, Laroche S (1997) Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat. J Neurophysiol 77:571–578PubMedGoogle Scholar
  41. Ebendal T (1992) Function and evolution in the NGF family and its receptors. J Neurosci Res 32:461–470PubMedGoogle Scholar
  42. Esser SK, Hill SL, Tononi G (2007) Sleep homeostasis and cortical synchronization: I. Modeling the effects of synaptic strength on sleep slow waves. Sleep 30:1617–1630PubMedCentralPubMedGoogle Scholar
  43. Faraguna U, Nelson A, Vyazovskiy VV, Cirelli C, Tononi G (2010) Unilateral cortical spreading depression affects sleep need and induces molecular and electrophysiological signs of synaptic potentiation in vivo. Cereb Cortex 20:2939–2947PubMedCentralPubMedGoogle Scholar
  44. Faraguna U, Vyazovskiy VV, Nelson AB, Tononi G, Cirelli C (2008) A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. J Neurosci 28:4088–4095PubMedGoogle Scholar
  45. Finelli LA, Baumann H, Borbely AA, Achermann P (2000) Dual electroencephalogram markers of human sleep homeostasis: correlation between theta activity in waking and slow-wave activity in sleep. Neuroscience 101:523–529PubMedGoogle Scholar
  46. Frank MG (2006) The mystery of sleep function: current perspectives and future directions. Rev Neurosci 17:375–392PubMedGoogle Scholar
  47. Franken P, Chollet D, Tafti M (2001) The homeostatic regulation of sleep need is under genetic control. J Neurosci 21:2610–2621PubMedGoogle Scholar
  48. Frey U, Schollmeier K, Reymann KG, Seidenbecher T (1995) Asymptotic hippocampal long-term potentiation in rats does not preclude additional potentiation at later phases. Neuroscience 67:799–807PubMedGoogle Scholar
  49. Fuhrmann G, Markram H, Tsodyks M (2002) Spike frequency adaptation and neocortical rhythms. J Neurophysiol 88:761–770PubMedGoogle Scholar
  50. Fujihara H, Sei H, Morita Y, Ueta Y, Morita K (2003) Short-term sleep disturbance enhances brain-derived neurotrophic factor gene expression in rat hippocampus by acting as internal stressor. J Mol Neurosci 21:223–232PubMedGoogle Scholar
  51. 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. Proc Natl Acad Sci USA 105:10227–10232PubMedCentralPubMedGoogle Scholar
  52. Gilestro GF, Tononi G, Cirelli C (2009) Widespread changes in synaptic markers as a function of sleep and wakefulness in Drosophila. Science 324:109–112PubMedCentralPubMedGoogle Scholar
  53. Giuditta A, Rutigliano B, Vitale-Neugebauer A (1980) Influence of synchronized sleep on the biosynthesis of RNA in neuronal and mixed fractions isolated from rabbit cerebral cortex. J Neurochem 35:1267–1272PubMedGoogle Scholar
  54. Gomez-Palacio-Schjetnan A, Escobar ML (2013) Neurotrophins and synaptic plasticity. Curr Top Behav Neurosci 15:117–136PubMedGoogle Scholar
  55. Green JD, Arduini AA (1954) Hippocampal electrical activity in arousal. J Neurophysiol 17:533–557PubMedGoogle Scholar
  56. Grivel J, Cvetkovic V, Bayer L, Machard D, Tobler I, Muhlethaler M, Serafin M (2005) The wake-promoting hypocretin/orexin neurons change their response to noradrenaline after sleep deprivation. J Neurosci 25:4127–4130PubMedGoogle Scholar
  57. Guzman-Marin R, Ying Z, Suntsova N, Methippara M, Bashir T, Szymusiak R, Gomez-Pinilla F, McGinty D (2006) Suppression of hippocampal plasticity-related gene expression by sleep deprivation in rats. J Physiol 575:807–819PubMedCentralPubMedGoogle Scholar
  58. Hagewoud R, Havekes R, Novati A, Keijser JN, Van der Zee EA, Meerlo P (2010) Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation. J Sleep Res 19:280–288PubMedGoogle Scholar
  59. Haider B, Duque A, Hasenstaub AR, McCormick DA (2006) Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition. J Neurosci 26:4535–4545PubMedGoogle Scholar
  60. Hairston IS, Peyron C, Denning DP, Ruby NF, Flores J, Sapolsky RM, Heller HC, O’Hara BF (2004) Sleep deprivation effects on growth factor expression in neonatal rats: a potential role for BDNF in the mediation of delta power. J Neurophysiol 91:1586–1595PubMedGoogle Scholar
  61. Hanlon EC, Faraguna U, Vyazovskiy VV, Tononi G, Cirelli C (2009) Effects of skilled training on sleep slow wave activity and cortical gene expression in the rat. Sleep 32:719–729PubMedCentralPubMedGoogle Scholar
  62. Hardingham N, Dachtler J, Fox K (2013) The role of nitric oxide in pre-synaptic plasticity and homeostasis. Front Cell Neurosci 7:190PubMedCentralPubMedGoogle Scholar
  63. Harris KD, Bartho P, Chadderton P, Curto C, de la Rocha J, Hollender L, Itskov V, Luczak A, Marguet SL, Renart A et al (2011) How do neurons work together? Lessons from auditory cortex. Hear Res 271:37–53PubMedCentralPubMedGoogle Scholar
  64. Harris KD, Thiele A (2011) Cortical state and attention. Nat Rev Neurosci 12:509–523PubMedCentralPubMedGoogle Scholar
  65. Hengen KB, Lambo ME, Van Hooser SD, Katz DB, Turrigiano GG (2013) Firing rate homeostasis in visual cortex of freely behaving rodents. Neuron 80:335–342PubMedGoogle Scholar
  66. Heynen AJ, Bear MF (2001) Long-term potentiation of thalamocortical transmission in the adult visual cortex in vivo. J Neurosci 21:9801–9813PubMedGoogle Scholar
  67. Hill S, Tononi G (2005) Modeling sleep and wakefulness in the thalamocortical system. J Neurophysiol 93:1671–1698PubMedGoogle Scholar
  68. Hinard V, Mikhail C, Pradervand S, Curie T, Houtkooper RH, Auwerx J, Franken P, Tafti M (2012) Key electrophysiological, molecular, and metabolic signatures of sleep and wakefulness revealed in primary cortical cultures. J Neurosci 32:12506–12517PubMedGoogle Scholar
  69. Hobson JA, McCarley RW (1971) Cortical unit activity in sleep and waking. Electroencephalogr Clin Neurophysiol 30:97–112PubMedGoogle Scholar
  70. Horne JA (1993) Human sleep, sleep loss and behaviour. Implications for the prefrontal cortex and psychiatric disorder. Br J Psychiatry 162:413–419PubMedGoogle Scholar
  71. Hsieh KC, Gvilia I, Kumar S, Uschakov A, McGinty D, Alam MN, Szymusiak R (2011) c-Fos expression in neurons projecting from the preoptic and lateral hypothalamic areas to the ventrolateral periaqueductal gray in relation to sleep states. Neuroscience 188:55–67PubMedCentralPubMedGoogle Scholar
  72. Huber R (2007) Memory formation: sleep enough before learning. Curr Biol 17:R367–R368PubMedGoogle Scholar
  73. Huber R, Deboer T, Tobler I (2000a) Effects of sleep deprivation on sleep and sleep EEG in three mouse strains: empirical data and simulations. Brain Res 857:8–19PubMedGoogle Scholar
  74. Huber R, Deboer T, Tobler I (2000b) Topography of EEG dynamics after sleep deprivation in mice. J Neurophysiol 84:1888–1893PubMedGoogle Scholar
  75. Huber R, Ghilardi MF, Massimini M, Ferrarelli F, Riedner BA, Peterson MJ, Tononi G (2006) Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity. Nat Neurosci 9:1169–1176PubMedGoogle Scholar
  76. Huber R, Ghilardi MF, Massimini M, Tononi G (2004) Local sleep and learning. Nature 430:78–81PubMedGoogle Scholar
  77. Huber R, Tononi G, Cirelli C (2007) Exploratory behavior, cortical BDNF expression, and sleep homeostasis. Sleep 30:129–139PubMedGoogle Scholar
  78. Hung CS, Sarasso S, Ferrarelli F, Riedner B, Ghilardi MF, Cirelli C, Tononi G (2013) Local experience-dependent changes in the wake EEG after prolonged wakefulness. Sleep 36:59–72PubMedCentralPubMedGoogle Scholar
  79. Ibata K, Sun Q, Turrigiano GG (2008) Rapid synaptic scaling induced by changes in postsynaptic firing. Neuron 57:819–826PubMedGoogle Scholar
  80. Ji D, Wilson MA (2007) Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci 10:100–107PubMedGoogle Scholar
  81. Jones BE (2005) From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci 26:578–586PubMedGoogle Scholar
  82. Jones SG, Vyazovskiy VV, Cirelli C, Tononi G, Benca RM (2008) Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii). BMC Neurosci 9:47PubMedCentralPubMedGoogle Scholar
  83. Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM (2009) Amyloid-beta dynamics are regulated by orexin and the sleep–wake cycle. Science 326:1005–1007PubMedCentralPubMedGoogle Scholar
  84. Kattler H, Dijk DJ, Borbely AA (1994) Effect of unilateral somatosensory stimulation prior to sleep on the sleep EEG in humans. J Sleep Res 3:159–164PubMedGoogle Scholar
  85. Kilduff TS, Cauli B, Gerashchenko D (2011) Activation of cortical interneurons during sleep: an anatomical link to homeostatic sleep regulation? Trends Neurosci 34:10–19PubMedCentralPubMedGoogle Scholar
  86. Killgore WD (2010) Effects of sleep deprivation on cognition. Prog Brain Res 185:105–129PubMedGoogle Scholar
  87. Kopp C, Longordo F, Nicholson JR, Luthi A (2006) Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function. J Neurosci 26:12456–12465PubMedGoogle Scholar
  88. Krueger JM, Obal F (1993) A neuronal group theory of sleep function. J Sleep Res 2:63–69PubMedGoogle Scholar
  89. Krueger JM, Obal FJ, Fang J, Kubota T, Taishi P (2001) The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci 933:211–221PubMedGoogle Scholar
  90. Krueger JM, Rector DM, Roy S, Van Dongen HP, Belenky G, Panksepp J (2008) Sleep as a fundamental property of neuronal assemblies. Nat Rev Neurosci 9:910–919PubMedCentralPubMedGoogle Scholar
  91. Krueger JM, Tononi G (2011) Local use-dependent sleep; synthesis of the new paradigm. Curr Top Med Chem 11:2490–2492PubMedCentralPubMedGoogle Scholar
  92. Kurth S, Ringli M, Geiger A, LeBourgeois M, Jenni OG, Huber R (2010) Mapping of cortical activity in the first two decades of life: a high-density sleep electroencephalogram study. J Neurosci 30:13211–13219PubMedCentralPubMedGoogle Scholar
  93. Lante F, Cavalier M, Cohen-Solal C, Guiramand J, Vignes M (2006) Developmental switch from LTD to LTP in low frequency-induced plasticity. Hippocampus 16:981–989PubMedGoogle Scholar
  94. Lapray D, Lasztoczi B, Lagler M, Viney TJ, Katona L, Valenti O, Hartwich K, Borhegyi Z, Somogyi P, Klausberger T (2012) Behavior-dependent specialization of identified hippocampal interneurons. Nat Neurosci 15:1265–1271PubMedCentralPubMedGoogle Scholar
  95. Leemburg S, Vyazovskiy VV, Olcese U, Bassetti CL, Tononi G, Cirelli C (2010) Sleep homeostasis in the rat is preserved during chronic sleep restriction. Proc Natl Acad Sci U S A 107:15939–15944PubMedCentralPubMedGoogle Scholar
  96. Liu ZW, Faraguna U, Cirelli C, Tononi G, Gao XB (2010) Direct evidence for wake-related increases and sleep-related decreases in synaptic strength in rodent cortex. J Neurosci 30:8671–8675PubMedCentralPubMedGoogle Scholar
  97. Lo JC, Groeger JA, Santhi N, Arbon EL, Lazar AS, Hasan S, von Schantz M, Archer SN, Dijk DJ (2012) Effects of partial and acute total sleep deprivation on performance across cognitive domains, individuals and circadian phase. PLoS One 7:e45987PubMedCentralPubMedGoogle Scholar
  98. Lockett GA, Wilkes F, Maleszka R (2010) Brain plasticity, memory and neurological disorders: an epigenetic perspective. NeuroReport 21:909–913PubMedGoogle Scholar
  99. Lu J, Greco MA, Shiromani P, Saper CB (2000) Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep. J Neurosci 20:3830–3842PubMedGoogle Scholar
  100. Lyamin OI, Pavlova IF, Kosenko PO, Mukhametov LM, Siegel JM (2012) Regional differences in cortical electroencephalogram (EEG) slow wave activity and interhemispheric EEG asymmetry in the fur seal. J Sleep Res 21:603–611PubMedGoogle Scholar
  101. Mackiewicz M, Shockley KR, Romer MA, Galante RJ, Zimmerman JE, Naidoo N, Baldwin DA, Jensen ST, Churchill GA, Pack AI (2007) Macromolecule biosynthesis: a key function of sleep. Physiol Genomics 31:441–457PubMedGoogle Scholar
  102. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21PubMedGoogle Scholar
  103. Maret S, Dorsaz S, Gurcel L, Pradervand S, Petit B, Pfister C, Hagenbuchle O, O’Hara BF, Franken P, Tafti M (2007) Homer1a is a core brain molecular correlate of sleep loss. Proc Natl Acad Sci USA 104:20090–20095PubMedCentralPubMedGoogle Scholar
  104. Maret S, Faraguna U, Nelson AB, Cirelli C, Tononi G (2011) Sleep and waking modulate spine turnover in the adolescent mouse cortex. Nat Neurosci 14:1418–1420PubMedCentralPubMedGoogle Scholar
  105. Martinez-Gonzalez D, Lesku JA, Rattenborg NC (2008) Increased EEG spectral power density during sleep following short-term sleep deprivation in pigeons (Columba livia): evidence for avian sleep homeostasis. J Sleep Res 17:140–153PubMedGoogle Scholar
  106. Marzano C, Ferrara M, Curcio G, Gennaro LD (2009) The effects of sleep deprivation in humans: topographical electroencephalogram changes in non-rapid eye movement (NREM) sleep versus REM sleep. J Sleep Res 19:260–268PubMedGoogle Scholar
  107. Massimini M, Ferrarelli F, Esser SK, Riedner BA, Huber R, Murphy M, Peterson MJ, Tononi G (2007) Triggering sleep slow waves by transcranial magnetic stimulation. Proc Natl Acad Sci USA 104:8496–8501PubMedCentralPubMedGoogle Scholar
  108. Massimini M, Huber R, Ferrarelli F, Hill S, Tononi G (2004) The sleep slow oscillation as a traveling wave. J Neurosci 24:6862–6870PubMedGoogle Scholar
  109. Massimini M, Rosanova M, Mariotti M (2003) EEG slow (approximately 1 Hz) waves are associated with nonstationarity of thalamo-cortical sensory processing in the sleeping human. J Neurophysiol 89:1205–1213PubMedGoogle Scholar
  110. McCormick DA (1992) Neurotransmitter actions in the thalamus and cerebral cortex. J Clin Neurophysiol 9:212–223PubMedGoogle Scholar
  111. McCormick DA, Connors BW, Lighthall JW, Prince DA (1985) Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J Neurophysiol 54:782–806PubMedGoogle Scholar
  112. McCoy JG, Strecker RE (2011) The cognitive cost of sleep lost. Neurobiol Learn Mem 96:564–582PubMedCentralPubMedGoogle Scholar
  113. McDermott CM, LaHoste GJ, Chen C, Musto A, Bazan NG, Magee JC (2003) Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci 23:9687–9695PubMedGoogle Scholar
  114. Meerlo P, Mistlberger RE, Jacobs BL, Heller HC, McGinty D (2009) New neurons in the adult brain: the role of sleep and consequences of sleep loss. Sleep Med Rev 13:187–194PubMedCentralPubMedGoogle Scholar
  115. Meerlo P, Pragt BJ, Daan S (1997) Social stress induces high intensity sleep in rats. Neurosci Lett 225:41–44PubMedGoogle Scholar
  116. Mignot E (2008) Why we sleep: the temporal organization of recovery. PLoS Biol 6:e106PubMedCentralPubMedGoogle Scholar
  117. Morairty SR, Dittrich L, Pasumarthi RK, Valladao D, Heiss JE, Gerashchenko D, Kilduff TS (2013) A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity. Proc Natl Acad Sci USA 110:20272–20277PubMedCentralPubMedGoogle Scholar
  118. Moruzzi G (1972) Sleep–Waking Cycle. Ergebnisse Der Physiologie Biologischen Chemie Und Experimentellen Pharmakologie 64:1–165Google Scholar
  119. Moser EI, Krobert KA, Moser MB, Morris RG (1998) Impaired spatial learning after saturation of long-term potentiation. Science 281:2038–2042PubMedGoogle Scholar
  120. Mukhametov LM, Supin AY, Polyakova IG (1977) Interhemispheric asymmetry of the electroencephalographic sleep patterns in dolphins. Brain Res 134:581–584PubMedGoogle Scholar
  121. Murphy M, Riedner BA, Huber R, Massimini M, Ferrarelli F, Tononi G (2009) Source modeling sleep slow waves. Proc Natl Acad Sci USA 106:1608–1613PubMedCentralPubMedGoogle Scholar
  122. Naidoo N, Giang W, Galante RJ, Pack AI (2005) Sleep deprivation induces the unfolded protein response in mouse cerebral cortex. J Neurochem 92:1150–1157PubMedGoogle Scholar
  123. Narayan P, Meehan S, Carver JA, Wilson MR, Dobson CM, Klenerman D (2012) Amyloid-beta oligomers are sequestered by both intracellular and extracellular chaperones. Biochemistry 51:9270–9276PubMedGoogle Scholar
  124. Nava E, Roder B (2011) Adaptation and maladaptation insights from brain plasticity. Prog Brain Res 191:177–194PubMedGoogle Scholar
  125. Nir Y, Staba RJ, Andrillon T, Vyazovskiy VV, Cirelli C, Fried I, Tononi G (2011) Regional slow waves and spindles in human sleep. Neuron 70:153–169PubMedCentralPubMedGoogle Scholar
  126. Nir Y, Vyazovskiy VV, Cirelli C, Banks MI, Tononi G (2013) Auditory Responses and stimulus-specific adaptation in rat auditory cortex are preserved across NREM and REM sleep. Cereb Cortex (in press)Google Scholar
  127. Noda H, Adey WR (1970) Firing of neuron pairs in cat association cortex during sleep and wakefulness. J Neurophysiol 33:672–684PubMedGoogle Scholar
  128. Obal F Jr, Krueger JM (2003) Biochemical regulation of non-rapid-eye-movement sleep. Front Biosci 8:d520–d550PubMedGoogle Scholar
  129. Okun M, Lampl I (2008) Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities. Nat Neurosci 11:535–537PubMedGoogle Scholar
  130. Oleksenko AI, Mukhametov LM, Polyakova IG, Supin AY, Kovalzon VM (1992) Unihemispheric sleep deprivation in bottlenose dolphins. J Sleep Res 1:40–44PubMedGoogle Scholar
  131. Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH (1997) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17:3727–3738PubMedGoogle Scholar
  132. Petersen CC, Hahn TT, Mehta M, Grinvald A, Sakmann B (2003) Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex. Proc Natl Acad Sci U S A 100:13638–13643PubMedCentralPubMedGoogle Scholar
  133. Piantoni G, Poil SS, Linkenkaer-Hansen K, Verweij IM, Ramautar JR, Van Someren EJ, Van Der Werf YD (2013) Individual differences in white matter diffusion affect sleep oscillations. J Neurosci 33:227–233PubMedGoogle Scholar
  134. Pickering M, Cumiskey D, O’Connor JJ (2005) Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol 90:663–670PubMedGoogle Scholar
  135. Pigarev IN, Nothdurft HC, Kastner S (1997) Evidence for asynchronous development of sleep in cortical areas. NeuroReport 8:2557–2560PubMedGoogle Scholar
  136. Porkka-Heiskanen T, Zitting KM, Wigren HK (2013) Sleep, its regulation and possible mechanisms of sleep disturbances. Acta Physiol (Oxf) 208:311–328Google Scholar
  137. Qiu S, Korwek KM, Weeber EJ (2006) A fresh look at an ancient receptor family: emerging roles for low density lipoprotein receptors in synaptic plasticity and memory formation. Neurobiol Learn Mem 85:16–29PubMedGoogle Scholar
  138. Rao Y, Liu ZW, Borok E, Rabenstein RL, Shanabrough M, Lu M, Picciotto MR, Horvath TL, Gao XB (2007) Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. J Clin Invest 117:4022–4033PubMedCentralPubMedGoogle Scholar
  139. Rattenborg NC (2006) Evolution of slow-wave sleep and palliopallial connectivity in mammals and birds: a hypothesis. Brain Res Bull 69:20–29PubMedGoogle Scholar
  140. Rattenborg NC, Amlaner CJ, Lima SL (2001) Unilateral eye closure and interhemispheric EEG asymmetry during sleep in the pigeon (Columba livia). Brain Behav Evol 58:323–332PubMedGoogle Scholar
  141. Rattenborg NC, Lima SL, Lesku JA (2012) Sleep locally, act globally. Neuroscientist 18:533–546PubMedGoogle Scholar
  142. Rechtschaffen A, Bergmann BM, Gilliland MA, Bauer K (1999) Effects of method, duration, and sleep stage on rebounds from sleep deprivation in the rat. Sleep 22:11–31PubMedGoogle Scholar
  143. Ribeiro S, Mello CV, Velho T, Gardner TJ, Jarvis ED, Pavlides C (2002) Induction of hippocampal long-term potentiation during waking leads to increased extrahippocampal zif-268 expression during ensuing rapid-eye-movement sleep. J Neurosci 22:10914–10923PubMedGoogle Scholar
  144. Ribeiro S, Shi X, Engelhard M, Zhou Y, Zhang H, Gervasoni D, Lin SC, Wada K, Lemos NA, Nicolelis MA (2007) Novel experience induces persistent sleep-dependent plasticity in the cortex but not in the hippocampus. Front Neurosci 1:43–55PubMedCentralPubMedGoogle Scholar
  145. Riedner BA, Hulse BK, Murphy MJ, Ferrarelli F, Tononi G (2011) Temporal dynamics of cortical sources underlying spontaneous and peripherally evoked slow waves. Prog Brain Res 193:201–218PubMedCentralPubMedGoogle Scholar
  146. Riedner BA, Vyazovskiy VV, Huber R, Massimini M, Esser S, Murphy M, Tononi G (2007) Sleep homeostasis and cortical synchronization: III. A high-density EEG study of sleep slow waves in humans. Sleep 30:1643–1657PubMedCentralPubMedGoogle Scholar
  147. Rinne A, Birk A, Bunemann M (2013) Voltage regulates adrenergic receptor function. Proc Natl Acad Sci USA 110:1536–1541PubMedCentralPubMedGoogle Scholar
  148. Rioult-Pedotti MS, Friedman D, Donoghue JP (2000) Learning-induced LTP in neocortex. Science 290:533–536PubMedGoogle Scholar
  149. Rioult-Pedotti MS, Friedman D, Hess G, Donoghue JP (1998) Strengthening of horizontal cortical connections following skill learning. Nat Neurosci 1:230–234PubMedGoogle Scholar
  150. Rusterholz T, Durr R, Achermann P (2010) Inter-individual differences in the dynamics of sleep homeostasis. Sleep 33:491–498PubMedCentralPubMedGoogle Scholar
  151. Sakata S, Harris KD (2009) Laminar structure of spontaneous and sensory-evoked population activity in auditory cortex. Neuron 64:404–418PubMedCentralPubMedGoogle Scholar
  152. Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE (2010) Sleep state switching. Neuron 68:1023–1042PubMedCentralPubMedGoogle Scholar
  153. Seibt J, Dumoulin MC, Aton SJ, Coleman T, Watson A, Naidoo N, Frank MG (2012) Protein synthesis during sleep consolidates cortical plasticity in vivo. Curr Biol 22:676–682PubMedCentralPubMedGoogle Scholar
  154. Sidrauski C, Chapman R, Walter P (1998) The unfolded protein response: an intracellular signalling pathway with many surprising features. Trends Cell Biol 8:245–249PubMedGoogle Scholar
  155. Sirota A, Montgomery S, Fujisawa S, Isomura Y, Zugaro M, Buzsaki G (2008) Entrainment of neocortical neurons and gamma oscillations by the hippocampal theta rhythm. Neuron 60:683–697PubMedCentralPubMedGoogle Scholar
  156. Stefan K, Wycislo M, Gentner R, Schramm A, Naumann M, Reiners K, Classen J (2006) Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training. Cereb Cortex 16:376–385PubMedGoogle Scholar
  157. Stellwagen D, Malenka RC (2006) Synaptic scaling mediated by glial TNF-alpha. Nature 440:1054–1059PubMedGoogle Scholar
  158. Steriade M, Contreras D, Curro Dossi R, Nunez A (1993a) The slow (<1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks. J Neurosci 13:3284–3299PubMedGoogle Scholar
  159. Steriade M, Nunez A, Amzica F (1993b) Intracellular analysis of relations between the slow (<1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. J Neurosci 13:3266–3283PubMedGoogle Scholar
  160. Steriade M, Nunez A, Amzica F (1993c) A novel slow (<1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J Neurosci 13:3252–3265PubMedGoogle Scholar
  161. Steriade M, Timofeev I, Grenier F (2001) Natural waking and sleep states: a view from inside neocortical neurons. J Neurophysiol 85:1969–1985PubMedGoogle Scholar
  162. Tartar JL, Ward CP, McKenna JT, Thakkar M, Arrigoni E, McCarley RW, Brown RE, Strecker RE (2006) Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation. Eur J Neurosci 23:2739–2748PubMedCentralPubMedGoogle Scholar
  163. Terao A, Steininger TL, Hyder K, Apte-Deshpande A, Ding J, Rishipathak D, Davis RW, Heller HC, Kilduff TS (2003) Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience 116:187–200PubMedGoogle Scholar
  164. Timofeev I, Grenier F, Bazhenov M, Sejnowski TJ, Steriade M (2000) Origin of slow cortical oscillations in deafferented cortical slabs. Cereb Cortex 10:1185–1199PubMedGoogle Scholar
  165. Tobler I (2005) Phylogeny of sleep regulation. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. W. B. Saunders, PhiladelphiaGoogle Scholar
  166. Tobler I, Borbely AA (1986) Sleep EEG in the rat as a function of prior waking. Electroencephalogr Clin Neurophysiol 64:74–76PubMedGoogle Scholar
  167. Tononi G, Cirelli C (2003) Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull 62:143–150PubMedGoogle Scholar
  168. Tononi G, Cirelli C (2006) Sleep function and synaptic homeostasis. Sleep Med Rev 10:49–62PubMedGoogle Scholar
  169. Tononi G, Cirelli C (2014) Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron 81:12–34PubMedCentralPubMedGoogle Scholar
  170. Turner TH, Drummond SP, Salamat JS, Brown GG (2007) Effects of 42 h of total sleep deprivation on component processes of verbal working memory. Neuropsychology 21:787–795PubMedGoogle Scholar
  171. Turrigiano GG (1999) Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same. Trends Neurosci 22:221–227PubMedGoogle Scholar
  172. Turrigiano GG (2008) The self-tuning neuron: synaptic scaling of excitatory synapses. Cell 135:422–435PubMedCentralPubMedGoogle Scholar
  173. Uschakov A, Grivel J, Cvetkovic-Lopes V, Bayer L, Bernheim L, Jones BE, Muhlethaler M, Serafin M (2011) Sleep-deprivation regulates alpha-2 adrenergic responses of rat hypocretin/orexin neurons. PLoS One 6:e16672PubMedCentralPubMedGoogle Scholar
  174. Van Dongen HP, Maislin G, Mullington JM, Dinges DF (2003) The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26:117–126PubMedGoogle Scholar
  175. Varshavsky A (2012) Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis. Protein Sci 21:1634–1661PubMedCentralPubMedGoogle Scholar
  176. Verkhratsky A, Petersen OH (2002) The endoplasmic reticulum as an integrating signalling organelle: from neuronal signalling to neuronal death. Eur J Pharmacol 447:141–154PubMedGoogle Scholar
  177. Verzeano M, Negishi K (1960) Neuronal activity in cortical and thalamic networks. J Gen Physiol 43(6)Suppl:177–195Google Scholar
  178. Volgushev M, Chauvette S, Mukovski M, Timofeev I (2006) Precise long-range synchronization of activity and silence in neocortical neurons during slow-wave oscillations [corrected]. J Neurosci 26:5665–5672PubMedGoogle Scholar
  179. Vyazovskiy V, Achermann P, Borbely AA, Tobler I (2004a) Interhemispheric coherence of the sleep electroencephalogram in mice with congenital callosal dysgenesis. Neuroscience 124:481–488PubMedGoogle Scholar
  180. Vyazovskiy V, Borbely AA, Tobler I (2000) Unilateral vibrissae stimulation during waking induces interhemispheric EEG asymmetry during subsequent sleep in the rat. J Sleep Res 9:367–371PubMedGoogle Scholar
  181. Vyazovskiy VV (2013) Cortical neuronal mechanisms of sleep homeostasis. Zh Vyssh Nerv Deiat Im I P Pavlova 63:13–23PubMedGoogle Scholar
  182. Vyazovskiy VV, Achermann P, Borbely AA, Tobler I (2004b) The dynamics of spindles and EEG slow-wave activity in NREM sleep in mice. Arch Ital Biol 142:511–523PubMedGoogle Scholar
  183. Vyazovskiy VV, Achermann P, Tobler I (2007a) Sleep homeostasis in the rat in the light and dark period. Brain Res Bull 74:37–44PubMedGoogle Scholar
  184. Vyazovskiy VV, Borbely AA, Tobler I (2002a) Interhemispheric sleep EEG asymmetry in the rat is enhanced by sleep deprivation. J Neurophysiol 88:2280–2286PubMedGoogle Scholar
  185. Vyazovskiy VV, Cirelli C, Pfister-Genskow M, Faraguna U, Tononi G (2008a) Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep. Nat Neurosci 11:200–208PubMedGoogle Scholar
  186. Vyazovskiy VV, Cirelli C, Tononi G (2011a) Electrophysiological correlates of sleep homeostasis in freely behaving rats. Prog Brain Res 193:17–38PubMedCentralPubMedGoogle Scholar
  187. Vyazovskiy VV, Cirelli C, Tononi G, Tobler I (2008b) Cortical metabolic rates as measured by 2-deoxyglucose-uptake are increased after waking and decreased after sleep in mice. Brain Res Bull 75:591–597PubMedCentralPubMedGoogle Scholar
  188. Vyazovskiy VV, Deboer T, Rudy B, Lau D, Borbely AA, Tobler I (2002b) Sleep EEG in mice that are deficient in the potassium channel subunit K.v.3.2. Brain Res 947:204–211PubMedGoogle Scholar
  189. Vyazovskiy VV, Faraguna U, Cirelli C, Tononi G (2009a) Triggering slow waves during NREM sleep in the rat by intracortical electrical stimulation: effects of sleep/wake history and background activity. J Neurophysiol 101:1921–1931PubMedCentralPubMedGoogle Scholar
  190. Vyazovskiy VV, Harris KD (2013) Sleep and the single neuron: the role of global slow oscillations in individual cell rest. Nat Rev Neurosci 14:443–451PubMedCentralPubMedGoogle Scholar
  191. Vyazovskiy VV, Olcese U, Cirelli C, Tononi G (2013) Prolonged wakefulness alters neuronal responsiveness to local electrical stimulation of the neocortex in awake rats. J Sleep Res 22: 239–250Google Scholar
  192. Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G (2011b) Local sleep in awake rats. Nature 472:443–447PubMedCentralPubMedGoogle Scholar
  193. Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, Cirelli C, Tononi G (2009b) Cortical firing and sleep homeostasis. Neuron 63:865–878PubMedCentralPubMedGoogle Scholar
  194. Vyazovskiy VV, Riedner BA, Cirelli C, Tononi G (2007b) Sleep homeostasis and cortical synchronization: II. A local field potential study of sleep slow waves in the rat. Sleep 30:1631–1642PubMedCentralPubMedGoogle Scholar
  195. Vyazovskiy VV, Ruijgrok G, Deboer T, Tobler I (2006) Running wheel accessibility affects the regional electroencephalogram during sleep in mice. Cereb Cortex 16:328–336PubMedGoogle Scholar
  196. Vyazovskiy VV, Tobler I (2005) Regional differences in NREM sleep slow-wave activity in mice with congenital callosal dysgenesis. J Sleep Res 14:299–304PubMedGoogle Scholar
  197. Vyazovskiy VV, Tobler I (2008) Handedness leads to interhemispheric EEG asymmetry during sleep in the rat. J Neurophysiol 99:969–975PubMedGoogle Scholar
  198. Vyazovskiy VV, Tobler I (2012) The temporal structure of behaviour and sleep homeostasis. PLoS One 7:e50677PubMedCentralPubMedGoogle Scholar
  199. Vyazovskiy VV, Tobler I, Winsky-Sommerer R (2007c) Alteration of behavior in mice by muscimol is associated with regional electroencephalogram synchronization. Neuroscience 147:833–841PubMedGoogle Scholar
  200. Vyazovskiy VV, Welker E, Fritschy JM, Tobler I (2004c) Regional pattern of metabolic activation is reflected in the sleep EEG after sleep deprivation combined with unilateral whisker stimulation in mice. Eur J Neurosci 20:1363–1370PubMedGoogle Scholar
  201. Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:1081–1086PubMedGoogle Scholar
  202. Werth E, Achermann P, Borbely AA (1996) Brain topography of the human sleep EEG: antero–posterior shifts of spectral power. NeuroReport 8:123–127PubMedGoogle Scholar
  203. Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science 313:1093–1097PubMedGoogle Scholar
  204. Winters BD, Huang YH, Dong Y, Krueger JM (2011) Sleep loss alters synaptic and intrinsic neuronal properties in mouse prefrontal cortex. Brain Res 1420:1–7PubMedCentralPubMedGoogle Scholar
  205. Xue X, Piao JH, Nakajima A, Sakon-Komazawa S, Kojima Y, Mori K, Yagita H, Okumura K, Harding H, Nakano H (2005) Tumor necrosis factor alpha (TNFalpha) induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNFalpha. J Biol Chem 280:33917–33925PubMedGoogle Scholar
  206. Yang G, Gan WB (2012) Sleep contributes to dendritic spine formation and elimination in the developing mouse somatosensory cortex. Dev Neurobiol 72:1391–1398PubMedCentralPubMedGoogle Scholar
  207. Yokoyama TK, Mochimaru D, Murata K, Manabe H, Kobayakawa K, Kobayakawa R, Sakano H, Mori K, Yamaguchi M (2011) Elimination of adult-born neurons in the olfactory bulb is promoted during the postprandial period. Neuron 71:883–897PubMedGoogle Scholar
  208. Yoo SS, Hu PT, Gujar N, Jolesz FA, Walker MP (2007) A deficit in the ability to form new human memories without sleep. Nat Neurosci 10:385–392PubMedGoogle Scholar
  209. Zavada A, Strijkstra AM, Boerema AS, Daan S, Beersma DG (2009) Evidence for differential human slow-wave activity regulation across the brain. J Sleep Res 18:3–10PubMedGoogle Scholar
  210. Ziemann U (2004) LTP-like plasticity in human motor cortex. Suppl Clin Neurophysiol 57:702–707PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
  2. 2.Department of Translational Research on New Technologies in Medicine and SurgeryUniversità di PisaPisaItaly

Personalised recommendations