pp 1-32 | Cite as

The Function(s) of Sleep

  • Marcos G. Frank
  • H. Craig HellerEmail author
Part of the Handbook of Experimental Pharmacology book series


Sleep is a highly conserved phenomenon in endotherms, and therefore it must serve at least one basic function across this wide range of species. What that function is remains one of the biggest mysteries in neurobiology. By using the word neurobiology, we do not mean to exclude possible non-neural functions of sleep, but it is difficult to imagine why the brain must be taken offline if the basic function of sleep did not involve the nervous system. In this chapter we discuss several current hypotheses about sleep function. We divide these hypotheses into two categories: ones that propose higher-order cognitive functions and ones that focus on housekeeping or restorative processes. We also pose four aspects of sleep that any successful functional hypothesis has to account for: why do the properties of sleep change across the life span? Why and how is sleep homeostatically regulated? Why must the brain be taken offline to accomplish the proposed function? And, why are there two radically different stages of sleep?

The higher-order cognitive function hypotheses we discuss are essential mechanisms of learning and memory and synaptic plasticity. These are not mutually exclusive hypotheses. Each focuses on specific mechanistic aspects of sleep, and higher-order cognitive processes are likely to involve components of all of these mechanisms. The restorative hypotheses are maintenance of brain energy metabolism, macromolecular biosynthesis, and removal of metabolic waste. Although these three hypotheses seem more different than those related to higher cognitive function, they may each contribute important components to a basic sleep function. Any sleep function will involve specific gene expression and macromolecular biosynthesis, and as we explain there may be important connections between brain energy metabolism and the need to remove metabolic wastes.

A deeper understanding of sleep functions in endotherms will enable us to answer whether or not rest behaviors in species other than endotherms are homologous with mammalian and avian sleep. Currently comparisons across the animal kingdom depend on superficial and phenomenological features of rest states and sleep, but investigations of sleep functions would provide more insight into the evolutionary relationships between EEG-defined sleep in endotherms and rest states in ectotherms.


Glycogen Glymphatic system Hippocampal place cells Learning Memory Ocular dominance plasticity Synaptic homeostasis Synaptic plasticity 


  1. Ackermann S, Rasch B (2014) Differential effects of non-REM and REM sleep on memory consolidation? Curr Neurol Neurosci Rep 14(2):430Google Scholar
  2. Albensi BC et al (2007) Electrical stimulation protocols for hippocampal synaptic plasticity and neuronal hyper-excitability: are they effective or relevant? Exp Neurol 204(1):1–13Google Scholar
  3. Andersen ML et al (2005) Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats. J Sleep Res 14(1):83–90Google Scholar
  4. Areal CC et al (2017) Sleep loss and structural plasticity. Curr Opin Neurobiol 44:1–7Google Scholar
  5. Arrigoni E et al (2009) Long-term synaptic plasticity is impaired in rats with lesions of the ventrolateral preoptic nucleus. Eur J Neurosci 30(11):2112–2120Google Scholar
  6. Aton SJ et al (2009a) The sedating antidepressant trazodone impairs sleep-dependent cortical plasticity. PLoS One 4(7):1–10Google Scholar
  7. Aton SJ et al (2009b) Mechanisms of sleep-dependent consolidation of cortical plasticity. Neuron 61(3):454–466Google Scholar
  8. Aton SJ et al (2013) Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons. PNAS 110(8):3101–3106Google Scholar
  9. Aton SJ et al (2014) Sleep promotes cortical response potentiation following visual experience. Sleep 37(7):1163–1170Google Scholar
  10. Basheer R et al (2005) Sleep deprivation-induced protein changes in basal forebrain: implications for synaptic plasticity. J Neurosci Res 82(5):650–658Google Scholar
  11. Bellesi M et al (2013) Effects of sleep and wake on oligodendrocytes and their precursors. J Neurosci 33(36):14288–14300Google Scholar
  12. Benington JH, Heller HC (1994) Does the function of REM sleep concern non-REM sleep or waking? Prog Neurobiol 44(5):433–449Google Scholar
  13. Benington J, Heller HC (1995) Restoration of brain energy metabolism as the function of sleep. Prog Neurobiol 45(4):347–360Google Scholar
  14. Benington JH et al (1995) Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res 692(1):79–85Google Scholar
  15. Blanco W et al (2015) Synaptic homeostasis and restructuring across the sleep-wake cycle. PLoS Comput Biol 11(5):e1004241Google Scholar
  16. Bobillier P et al (1971) Deprivation of paradoxical sleep and in vitro cerebral protein synthesis in the rat. Life Sci 10(Part II):1349–1357Google Scholar
  17. Bonhoeffer T, Grinvald A (1996) Optical imaging based on intrinsic signal. The methodology. In: Toga AW, Massiotta HC (eds) Brain mapping: the methods. Academic Press, London, pp 55–97Google Scholar
  18. Borbely AA, Achermann P (1992) Concepts and models of sleep regulation: an overview. J Sleep Res 1(2):63–79Google Scholar
  19. Born J, Wilhelm I (2012) System consolidation of memory during sleep. Psychol Res 76(2):192–203Google Scholar
  20. Cai DJ et al (2009) Sleep selectively enhances hippocampus-dependent memory in mice. Behav Neurosci 123(4):713–719Google Scholar
  21. Campbell IG et al (2002) Sleep deprivation impairs long-term potentiation in the rat hippocampal slices. J Neurophysiol 88:1073–1076Google Scholar
  22. Chen C et al (2006) Altered NMDA receptor trafficking contributes to sleep deprivation-induced hippocampal synaptic and cognitive impairments. Biochem Biophys Res Commun 340(2):435–440Google Scholar
  23. Cirelli C, Tononi G (2015) Sleep and synaptic homeostasis. Sleep 38(1):161–162Google Scholar
  24. Cirelli C et al (2004) Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron 41(1):35–43Google Scholar
  25. Cooke SF, Bear MF (2010) Visual experience induces long-term potentiation in the primary visual cortex. J Neurosci 30(48):16304–16313Google Scholar
  26. Czikk MJ et al (2003) Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state. Am J Physiol Regul Integr Comp Physiol 284(1):R200–R207Google Scholar
  27. Davidson TJ et al (2009) Hippocampal replay of extended experience. Neuron 63(4):497–507Google Scholar
  28. Davis CJ et al (2003) REM sleep deprivation-induced deficits in the latency-to-peak induction and maintenance of long-term potentiation within the CA1 region of the hippocampus. Brain Res 973(2):293–297Google Scholar
  29. Davis CJ et al (2006) REM sleep deprivation attenuates actin-binding protein cortactin: a link between sleep and hippocampal plasticity. Neurosci Lett 400(3):191–196Google Scholar
  30. de Sanchez VC et al (1993) Day-night variations of adenosine and its metabolizing enzymes in the brain cortex of the rat – possible physiological significance for the energetic homeostasis and the sleep-wake cycle. Brain Res 612:115–121Google Scholar
  31. de Vivo L et al (2017) Ultrastructural evidence for synaptic scaling across the wake/sleep cycle. Science 355(6324):507Google Scholar
  32. Denin NN et al (1980) Concentration of proteins and RNA in neurons and gliocytes of the rat locus coeruleus during natural sleep and REM-sleep deprivation. Fiziol ZH SSSR Im I Sechnonovia 66(11):1626–1631Google Scholar
  33. Diering GH et al (2017) Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science 355(6324):511Google Scholar
  34. Dumoulin Bridi MC et al (2015) Rapid eye movement sleep promotes cortical plasticity in the developing brain. Sci Adv 1(6):e1500105Google Scholar
  35. Dumoulin MC et al (2015) Extracellular signal-regulated kinase (ERK) activity during sleep consolidates cortical plasticity in vivo. Cereb Cortex 25(2):507–515Google Scholar
  36. Durkin J, Aton SJ (2016) Sleep-dependent potentiation in the visual system is at odds with the synaptic homeostasis hypothesis. Sleep 39:155–159Google Scholar
  37. Durkin J et al (2017) Cortically coordinated NREM thalamocortical oscillations play an essential, instructive role in visual system plasticity. Proc Natl Acad Sci 114(39):10485–10490Google Scholar
  38. Ego-Stengel V, Wilson MA (2010) Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus 20(1):1–10Google Scholar
  39. Endo T et al (1997) Selective and total sleep deprivation: effect on the sleep EEG in the rat. Psychiatry Res 66:97–110Google Scholar
  40. Endo T et al (1998) Selective REM sleep deprivation in humans: effects on sleep and sleep EEG. Am J Phys 274(4 Pt 2):R1186–R1194Google Scholar
  41. Espinosa JS, Stryker MP (2012) Development and plasticity of the primary visual cortex. Neuron 75(2):230–249Google Scholar
  42. Falkowska A et al (2015) Energy metabolism of the brain, including the cooperation between astrocytes and neurons, especially in the context of glycogen metabolism. Int J Mol Sci 16(11):25959–25981Google Scholar
  43. Faraguna U et al (2008) A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. J Neurosci 28(15):4088–4095Google Scholar
  44. Faraguna U et al (2010) Unilateral cortical spreading depression affects sleep need and induces molecular and electrophysiological signs of synaptic potentiation in vivo. Cereb Cortex 20(12):2939–2947Google Scholar
  45. Farooqui SM et al (1996) Changes in monoamines and their metabolite concentrations in REM sleep-deprived rat forebrain nuclei. Pharmacol Biochem Behav 54(2):385–391Google Scholar
  46. Florian C et al (2011) Astrocyte-derived adenosine and A1 receptor activity contribute to sleep loss-induced deficits in hippocampal synaptic plasticity and memory in mice. J Neurosci 31(19):6956–6962Google Scholar
  47. Foster DJ (2017) Replay comes of age. Annu Rev Neurosci 40(1):581–602Google Scholar
  48. Frank MG (2005) Sleep, synaptic plasticity and the developing brain. In: Luppi P-H (ed) Sleep circuits and functions. CRC Press, Boca Raton, pp 177–192Google Scholar
  49. Frank MG (2006) The mystery of sleep function: current perspectives and future directions. Rev Neurosci 17:375–392Google Scholar
  50. Frank MG (2010) The functions of sleep. In: Winkelman JW, Plante DT (eds) Foundations of psychiatric sleep medicine. Cambridge University Press, Cambridge, pp 59–78Google Scholar
  51. Frank MG (2012) Erasing synapses in sleep: is it time to be SHY? Neural Plast 2012:264–378Google Scholar
  52. Frank MG (2013) Why I’m not shy: a reply to Tononi and Cirelli. Neural Plast 2013:394946Google Scholar
  53. Frank M (2015) Sleep and synaptic plasticity in the developing and adult brain. Curr Top Behav Neurosci 25:123–149Google Scholar
  54. Frank MG, Cantera R (2014) Sleep, clocks, and synaptic plasticity. Trends Neurosci 37(9):491–501Google Scholar
  55. Frank M, Issa NP, Stryker MP (2001) Sleep enhances plasticity in the developing visual cortex. Neuron 30:275–287Google Scholar
  56. Franken P et al (2003) Changes in brain glycogen after sleep deprivation vary with genotype. Am J Physiol Regul Integr Comp Physiol 285(2):R413–R419Google Scholar
  57. Frenkel MY et al (2006) Instructive effect of visual experience in mouse visual cortex. Neuron 51(3):339–349Google Scholar
  58. Fujisawa S, Buzsáki G (2011) A 4 Hz oscillation adaptively synchronizes prefrontal, VTA, and hippocampal activities. Neuron 72(1):153–165Google Scholar
  59. Gip P et al (2002) Sleep deprivation decreases glycogen in the cerebellum but not in the cortex of young rats. Am J Physiol Regul Integr Comp Physiol 283(1):R54–R59Google Scholar
  60. Girardeau G et al (2009) Selective suppression of hippocampal ripples impairs spatial memory. Nat Neurosci 12:1222Google Scholar
  61. Giuditta A et al (1980a) Influence of synchronized sleep on the biosynthesis of RNA in neuronal and mixed fractions isolated from rabbit cerebral cortex. J Neurochem 35(6):1267–1272Google Scholar
  62. Giuditta A et al (1980b) Influence of synchronized sleep on the biosynthesis of RNA in two nuclear classes isolated from rabbit cerebral cortex. J Neurochem 35(6):1259–1266Google Scholar
  63. Giuditta A et al (1995) The sequential hypothesis of the function of sleep. Behav Brain Res 69:157–166Google Scholar
  64. Graves LA et al (2003) Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning. Learn Mem 10(3):168–176Google Scholar
  65. Greene RW et al (2017) The adenosine-mediated, neuronal-glial, homeostatic sleep response. Curr Opin Neurobiol 44:236–242Google Scholar
  66. Guzman-Marin R et al (2003) Sleep deprivation reduces proliferation of cells in the dentate gyrus of the hippocampus in rats. J Physiol Lond 549(2):563–571Google Scholar
  67. Guzman-Marin R et al (2005) Sleep deprivation suppresses neurogenesis in the adult hippocampus of rats. Eur J Neurosci 22(8):2111–2116Google Scholar
  68. Guzman-Marin R et al (2006) Suppression of hippocampal plasticity-related gene expression by sleep deprivation. J Physiol Lond 575(Pt 3):807–819Google Scholar
  69. Guzman-Marin R et al (2008) Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat. Sleep 31(2):167–175Google Scholar
  70. Hagewoud R et al (2009) Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation. J Sleep Res 19(2):280–288Google Scholar
  71. Hairston IS et al (2005) Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning. J Neurophysiol 94(6):4224–4233Google Scholar
  72. Halassa MM et al (2009) Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61(2):213–219Google Scholar
  73. Hall-Porter JM et al (2014) The effect of two benzodiazepine receptor agonist hypnotics on sleep-dependent memory consolidation. J Clin Sleep Med 10(1):27–34Google Scholar
  74. Havekes R, Abel T (2017) The tired hippocampus: the molecular impact of sleep deprivation on hippocampal function. Curr Opin Neurobiol 44:13–19Google Scholar
  75. Havekes R et al (2007) The tired hippocampus: effects of sleep deprivation on AMPA receptor function and cell proliferation. Sleep Biol Rhythms 5(Supplement 1):A48Google Scholar
  76. Havekes R et al (2016) Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1. elife 5:e13424Google Scholar
  77. Heller HC et al (2014) Adaptive and pathological inhibition of neuroplasticity associated with circadian rhythms and sleep. Behav Neurosci 128(3):273–282Google Scholar
  78. Hendricks JC et al (2000a) Rest in drosophila is a sleep-like state. Neuron 25(1):129–138Google Scholar
  79. Hendricks JC et al (2000b) The need for a simple animal model to understand sleep. Prog Neurobiol 61(4):339–351Google Scholar
  80. Hengen KB et al (2016) Neuronal firing rate homeostasis is inhibited by sleep and promoted by wake. Cell 165(1):180–191Google Scholar
  81. Herculano-Houzel S (2013) Sleep it out. Science 342(6156):316–317Google Scholar
  82. Hill S et al (2008) Sleep improves the variability of motor performance. Brain Res Bull 76(6):605–611Google Scholar
  83. Hipolide DC et al (1998) Heterogeneous effects of rapid eye movement sleep deprivation on binding to [alpha]- and [beta]-adrenergic receptor subtypes in rat brain. Neuroscience 86(3):977–987Google Scholar
  84. Hobson JA (1999) Neural control of sleep. In: Turek FW, Zee PC (eds) Regulation of sleep and circadian rhythms, vol 133. Marcel Dekker, New York, pp 81–110Google Scholar
  85. Holscher C (1999) Synaptic plasticity and learning and memory: LTP and beyond. J Neurosci Res 58:62–75Google Scholar
  86. Hubel DH, Wiesel TN (1970) The period of susceptibility to the physiological effects of unilateral eye closure in kittens. J Physiol 206:419–436Google Scholar
  87. Huber R (2007) TMS-induced cortical potentiation during wakefulness locally increases slow wave activity during sleep. PLoS One 2:e276Google Scholar
  88. Huber R, Ghilardi MF, Massimini M, Tononi G (2004) Local sleep and learning. Nature 430:78–81Google Scholar
  89. Huerta PT, Lisman JE (1996) Low-frequency stimulation at the troughs of theta-oscillation induces long-term depression of previously potentiated CA1 synapses. J Neurophysiol 75(2):877–884Google Scholar
  90. Hulme SR et al (2014) Mechanisms of heterosynaptic metaplasticity. Philos Trans R Soc Lond B Biol Sci 369(1633):20130148Google Scholar
  91. Iliff JJ, Nedergaard M (2013) Is there a cerebral lymphatic system? Stroke 44(6 suppl 1):S93Google Scholar
  92. Inoki K et al (2012) AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol 52(1):381–400Google Scholar
  93. Ishikawa A et al (2006) Selective rapid eye movement sleep deprivation impairs the maintenance of long-term potentiation in the rat hippocampus. Eur J Neurosci 24(1):243–248Google Scholar
  94. Jha SK et al (2005) Sleep-dependent plasticity requires cortical activity. J Neurosci 25(40):9266–9274Google Scholar
  95. Ji D, Wilson MA (2007) Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci 10(1):100–106Google Scholar
  96. Kaplan ES et al (2016) Contrasting roles for parvalbumin-expressing inhibitory neurons in two forms of adult visual cortical plasticity. elife 5:e11450Google Scholar
  97. Khodagholy D et al (2017) Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus. Science 358(6361):369Google Scholar
  98. Kim E et al (2005) REM sleep deprivation inhibits LTP in vivo in area CA1 of rat hippocampus. Neurosci Lett 388(3):163–167Google Scholar
  99. Kong J et al (2002) Brain glycogen decreases with increased periods of wakefulness: implications for homeostatic drive to sleep. J Neurosci 22(13):5581–5587Google Scholar
  100. Kopp C et al (2006) Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function. J Neurosci 26(48):12456–12465Google Scholar
  101. Lee AK, Wilson MA (2002) Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36:1183–1194Google Scholar
  102. Li W et al (2017) REM sleep selectively prunes and maintains new synapses in development and learning. Nat Neurosci 20(3):427–437Google Scholar
  103. Liu Z-W et al (2010) Direct evidence for wake-related increases and sleep-related decreases in synaptic strength in rodent cortex. J Neurosci 30(25):8671–8675Google Scholar
  104. Longordo F et al (2009) NR2A at CA1 synapses is obligatory for the susceptibility of hippocampal plasticity to sleep loss. J Neurosci 29(28):9026–9041Google Scholar
  105. Louie K, Wilson MA (2001) Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron 29:145–156Google Scholar
  106. Lundgaard I et al (2016) Glymphatic clearance controls state-dependent changes in brain lactate concentration. J Cereb Blood Flow Metab 37(6):2112–2124Google Scholar
  107. Mackiewicz M et al (2007) Macromolecule biosynthesis – a key function of sleep. Physiol Genomics 31:441–457Google Scholar
  108. Majumdar S, Mallick BN (2005) Cytomorphometric changes in rat brain neurons after rapid eye movement sleep deprivation. Neuroscience 135(3):679–690Google Scholar
  109. Maloney KJ et al (2002) c-Fos expression in dopaminergic and GABAergic neurons of the ventral mesencephalic tegmentum after paradoxical sleep deprivation and recovery. Eur J Neurosci 15(4):774–778Google Scholar
  110. Maret S et al (2011) Sleep and waking modulate spine turnover in the adolescent mouse cortex. Nat Neurosci 14:1418–1420Google Scholar
  111. Marks CA, Wayner MJ (2005) Effects of sleep disruption on rat dentate granule cell LTP in vivo. Brain Res Bull 66(2):114–119Google Scholar
  112. McDermott CM et al (2003) Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci 23(29):9687–9695Google Scholar
  113. McDermott CM et al (2006) Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus. J Physiol Lond 570(3):553–565Google Scholar
  114. Mehta MR (2007) Cortico-hippocampal interaction during up-down states and memory consolidation. Nat Neurosci 10:13Google Scholar
  115. Merchant-Nancy H et al (1992) c-fos proto-oncogene changes in relation to REM sleep duration. Brain Res 579(2):342–346Google Scholar
  116. Molle M et al (2006) Hippocampal sharp wave-ripples linked to slow oscillations in rat slow-wave sleep. J Neurophysiol 96:62–70Google Scholar
  117. Mueller AD et al (2008) Sleep deprivation can inhibit adult hippocampal neurogenesis independent of adrenal stress hormones. Am J Physiol Regul Integr Comp Physiol 294(5):R1693–R1703Google Scholar
  118. Naidoo N et al (2005) Sleep deprivation induces the unfolded protein response in mouse cerebral cortex. J Neurochem 92(5):1150–1157Google Scholar
  119. Nakanishi H et al (1997) Positive correlations between cerebral protein synthesis rates and deep sleep in Macaca mulatta. Eur J Neurosci 9:271–279Google Scholar
  120. Nere AT et al (2013) Sleep dependent synaptic down-selection (I): modeling the benefits of sleep on memory consolidation and integration. Front Neurol 4:143Google Scholar
  121. Norimoto H et al (2018) Hippocampal ripples down-regulate synapses. Science 359:1524–1527Google Scholar
  122. O’Donnell C, Sejnowski TJ (2014) Selective memory generalization by spatial patterning of protein synthesis. Neuron 82(2):398–412Google Scholar
  123. Olcese U et al (2010) Sleep and synaptic renormalization: a computational study. J Neurophysiol 104(6):3476–3493Google Scholar
  124. Oudiette D, Paller KA (2013) Upgrading the sleeping brain with targeted memory reactivation. Trends Cogn Sci 17(3):142–149Google Scholar
  125. Palchykova S et al (2010) Manipulation of adenosine kinase affects sleep regulation in mice. J Neurosci 30(39):13157–13165Google Scholar
  126. Pedrazzoli M, Benedito MAC (2004) Rapid eye movement sleep deprivation-induced down-regulation of beta-adrenergic receptors in the rat brainstem and hippocampus. Pharmacol Biochem Behav 79(1):31–36Google Scholar
  127. Petit J-M et al (2002) Sleep deprivation modulates brain mRNAs encoding genes of glycogen metabolism. Eur J Neurosci 16(6):1163–1167Google Scholar
  128. Petit J-M et al (2015) Glycogen metabolism and the homeostatic regulation of sleep. Metab Brain Dis 30(1):263–279Google Scholar
  129. Poe GR, Nitz DA, McNaughton BL, Barnes DA (2000) Experience-dependent phase-reversal of hippocampal neuron firing during REM sleep. Brain Res 855:176–180Google Scholar
  130. Porkka-Heiskanen T et al (1997) Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276(5316):1265–1268Google Scholar
  131. Porrka-Heiskanen T et al (1995) Noradrenergic activity in rat brain during rapid eye movement sleep deprivation and rebound sleep. Am J Physiol 268(37):R1456–R1463Google Scholar
  132. Prichard J et al (1991) Lactate rise detected by 1H NMR in human visual cortex during physiological stimulation. PNAS 88:5829–5831Google Scholar
  133. Puentes-Mestril C, Aton SJ (2017) Linking network activity to synaptic plasticity during sleep: hypotheses and recent data. Front Neural Circuits 11:61Google Scholar
  134. Radulovacki M et al (1984) Adenosine analogs and sleep in rats. J Pharmacol Exp Ther 228(2):268–274Google Scholar
  135. Ramirez S, Tonegawa D, Liu X (2013) Identification and optogenetic manipulation of memory engrams in the hippocampus. Front Behav Neurosci 7:226Google Scholar
  136. Ramm P, Smith CT (1990) Rates of cerebral protein synthesis are linked to slow-wave sleep in the rat. Physiol Behav 48:749–753Google Scholar
  137. Rasch B, Born J (2007) Maintaining memories by reactivation. Curr Opin Neurobiol 17:698–703Google Scholar
  138. Rasch B, Born J (2013) About sleep’s role in memory. Physiol Rev 93(2):681–766Google Scholar
  139. Ravassard P et al (2006) Paradoxical sleep amount modulates neuronal plasticity in adult rat hippocampus. J Sleep Res 15:191–191Google Scholar
  140. Ravassard P et al (2009) Paradoxical (REM) sleep deprivation causes a large and rapidly reversible decrease in long-term potentiation, synaptic transmission, glutamate receptor protein levels, and ERK/MAPK activation in the dorsal hippocampus. Sleep 32(2):227–240Google Scholar
  141. Ravassard P et al (2015) REM sleep-dependent bidirectional regulation of hippocampal-based emotional memory and LTP. Cereb Cortex 26:1488–1500Google Scholar
  142. Rechtschaffen A (1998) Current perspectives on the function of sleep. Perspect Biol Med 41(3):359–390Google Scholar
  143. Rechtschaffen A et al (2002) Sleep deprivation in the rat: X. Integration and discussion of the findings. 1989. Sleep 25(1):68–87Google Scholar
  144. Ribeiro S (2011) Sleep and plasticity. Pfluegers Arch Eur J Physiol 463:111–120Google Scholar
  145. Rolls A et al (2013) Sleep to forget: interference of fear memories during sleep. Mol Psychiatry 18:1166Google Scholar
  146. Romcy-Pereira R, Pavlides C (2004) Distinct modulatory effects of sleep on the maintenance of hippocampal and medial prefrontal cortex LTP. Eur J Neurosci 20(12):3453–3462Google Scholar
  147. Rudoy JD et al (2009) Strengthening individual memories by reactivating them during sleep. Science 326(5956):1079Google Scholar
  148. Sadowski JH et al (2016) Sharp-wave ripples orchestrate the induction of synaptic plasticity during reactivation of place cell firing patterns in the hippocampus. Cell Rep 14(8):1916–1929Google Scholar
  149. Seibt J et al (2008) The non-benzodiazepine hypnotic Zolpidem impairs sleep-dependent cortical plasticity. Sleep 31(10):1381–1392Google Scholar
  150. Seibt J et al (2012) Protein synthesis during sleep consolidates cortical plasticity in vivo. Curr Biol 22(8):676–682Google Scholar
  151. Seibt J et al (2017) Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents. Nat Commun 8(1):684Google Scholar
  152. Sengpiel F (2001) Cortical plasticity: learning while you sleep? Curr Biol 11(16):R647–R650Google Scholar
  153. Shapiro C, Girdwood P (1981) Protein synthesis in rat brain during sleep. Neuropharmacology 20:457–460Google Scholar
  154. Shaw PJ et al (2000) Correlates of sleep and waking in Drosophila melanogaster. Science 287(5459):1834–1837Google Scholar
  155. Siapas AG et al (2005) Prefrontal phase locking to hippocampal theta oscillations. Neuron 46(1):141–151Google Scholar
  156. Smith C (2001) Sleep states and memory processes in humans: procedural versus declarative memory systems. Sleep Med Rev 5:491–506Google Scholar
  157. Smith GB et al (2009) Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex. Philos Trans R Soc Lond B Biol Sci 364(1515):357–367Google Scholar
  158. Soulé J et al (2012) Balancing arc synthesis, mRNA decay, and proteasomal degradation. J Biol Chem 287(26):22354–22366Google Scholar
  159. Spolidoro M et al (2008) Plasticity in the adult brain: lessons from the visual system. Exp Brain Res 192:335–341Google Scholar
  160. Steriade M, Timofeev I (2003) Neuronal plasticity in thalamocortical networks during sleep and waking oscillations. Neuron 37(4):563–576Google Scholar
  161. Stickgold R (2005) Sleep-dependent memory consolidation. Nature 437(7063):1272–1278Google Scholar
  162. Taishi P et al (2001) Conditions that affect sleep alter the expression of molecules associated with synaptic plasticity. Am J Phys 281:R839–R845Google Scholar
  163. Tartar JL et al (2006) Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation. Eur J Neurosci 23(10):2739–2748Google Scholar
  164. Terao A et al (2003) Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience 116(1):187–200Google Scholar
  165. Timofeev I, Chauvette S (2017) Sleep slow oscillation and plasticity. Curr Opin Neurobiol 44:116–126Google Scholar
  166. Tobler I (2005) Phylogeny of sleep regulation. In: Kryger M, Roth T, Dement WC (eds) Principles and practice of sleep medicine. W. B. Saunders, Philadelphia, pp 72–90Google Scholar
  167. Tononi G, Cirelli C (2003) Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull 62(2):143–150Google Scholar
  168. Tononi G, Cirelli C (2006) Sleep function and synaptic homeostasis. Sleep Med Rev 10(1):49–62Google 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(1):12–34Google Scholar
  170. Toppila J et al (1995) REM sleep deprivation induces galanin gene expression in the rat brain. Neurosci Lett 183(3):171–174Google Scholar
  171. Tropea D et al (2009) Molecular mechanisms of experience-dependent plasticity in visual cortex. Philos Trans R Soc Lond B Biol Sci 364(1515):341–355Google Scholar
  172. Tsanov M, Manahan-Vaughan D (2007) The adult visual cortex expresses dynamic synaptic plasticity that is driven by the light/dark cycle. J Neurosci 27(31):8414–8421Google Scholar
  173. Tudor JC et al (2016) Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis. Sci Signal 9(425):ra41Google Scholar
  174. Tung A et al (2005) Effects of sleep deprivation and recovery sleep upon cell proliferation in adult rat dentate gyrus. Neuroscience 134(3):721–723Google Scholar
  175. Turrigiano G (2007) Homeostatic signaling: the positive side of negative feedback. Curr Opin Neurobiol 17:318–324Google Scholar
  176. van Dongen EV et al (2012) Memory stabilization with targeted reactivation during human slow-wave sleep. Proc Natl Acad Sci 109(26):10575–10580Google Scholar
  177. Vazquez J et al (2008) Rapid alterations in cortical protein profiles underlie spontaneous sleep and wake bouts. J Cell Biochem 105:1472–1484Google Scholar
  178. Vecsey CG et al (2009) Sleep deprivation impairs cAMP signalling in the hippocampus. Nature 461(7267):1122–1125Google Scholar
  179. Vecsey CG et al (2012) Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus. Physiol Genomics 44(20):981–991Google Scholar
  180. Vyazovskiy VV et al (2008) Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep. Nat Neurosci 11(2):200–208Google Scholar
  181. Vyazovskiy VV et al (2009) Cortical firing and sleep homeostasis. Neuron 63(6):865–878Google Scholar
  182. Watson BO et al (2016) Network homeostasis and state dynamics of neocortical sleep. Neuron 90(4):839–852Google Scholar
  183. Wierzynski CM, Lubenov EV, Gu M, Siapas AG (2009) State-dependent spike-timing relationships between hippocampal and prefrontal circuits during sleep. Neuron 61(4):587–596Google Scholar
  184. Wiesel TN, Hubel DH (1963) Single cell responses in striate cortex of kittens deprived of vision in one eye. J Neurophysiol 28:1029–1040Google Scholar
  185. Wilson MA, McNaughton BL (1994) Reactivation of hippocampal ensemble memories during sleep. Science 265:676–682Google Scholar
  186. Xie L et al (2013) Sleep drives metabolite clearance from the adult brain. Science 342(6156):373–377Google Scholar
  187. Yang G, Gan W-B (2011) Sleep contributes to dendritic spine formation and elimination in the developing mouse somatosensory cortex. Dev Neurobiol 72:1391–1398Google Scholar
  188. Yang G et al (2014) Sleep promotes branch-specific formation of dendritic spines after learning. Science 344(6188):1173–1178Google Scholar
  189. Zimmerman JE et al (2004) Glycogen in the brain of Drosophila melanogaster: diurnal rhythm and the effect of rest deprivation. J Neurochem 88(1):32–40Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomedical SciencesElson S. Floyd College of Medicine, Washington State University SpokaneSpokaneUSA
  2. 2.Department of BiologyStanford UniversityStanfordUSA

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