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Cited by 130Sleep and Wakefulness ResearchNeuroscience and Neuropharmacology ResearchNeuroscience of respiration and sleep

Brain energetics during the sleep-wake cycle

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DiNuzzo, Mauro, Nedergaard, Maiken·2017·Current Opinion in Neurobiology
DOI 10.1016/j.conb.2017.09.010PMC PMC5732842
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Abstract

Brain activity during wakefulness is associated with high metabolic rates that are believed to support information processing and memory encoding. In spite of loss of consciousness, sleep still carries a substantial energy cost. Experimental evidence supports a cerebral metabolic shift taking place during sleep that suppresses aerobic glycolysis, a hallmark of environment-oriented waking behavior and synaptic plasticity. Recent studies reveal that glial astrocytes respond to the reduction of wake-promoting neuromodulators by regulating volume, composition and glymphatic drainage of interstitial fluid. These events are accompanied by changes in neuronal discharge patterns, astrocyte-neuron interactions, synaptic transactions and underlying metabolic features. Internally-generated neuronal activity and network homeostasis are proposed to account for the high sleep-related energy demand.

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  • The local input-output balance between neuronal synaptic/spiking (or subthreshold/suprathreshold) activity is a primary determinant in the upregulation of aerobic glycolysis.

    “Based on experimental evidence and metabolic modeling, we have previously proposed that the local input–output balance between neuronal synaptic/spiking (or subthreshold/suprathreshold) activity is a primary determinant in the upregulation of aerobic glycolysis (DiNuzzo and Giove, 2012; DiNuzzo et al., 2011; DiNuzzo and Nedergaard, 2017).”

    From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as DiNuzzo and Nedergaard, 2017

    The section on state-dependent astrocyte–neuron interactions says the balance between presynaptic and postsynaptic activation may account for changes in the oxygen-glucose index during the sleep–wake cycle, which bears on aerobic glycolysis. It does not identify the synaptic-versus-spiking (subthreshold-versus-suprathreshold) input–output balance as a primary determinant of aerobic glycolysis upregulation. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Elevated brain lactate and glutamate levels are associated with wakefulness and memory formation, which naturally require the processing of incoming sensory stimuli.

    “Elevated brain lactate and glutamate levels are associated with wakefulness and memory formation, which naturally require the processing of incoming sensory stimuli”

    From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as DiNuzzo and Nedergaard, 2017

    The “Oxidative shift in brain energy metabolism during state transitions” section reports higher extracellular glutamate during wakefulness than NREM sleep, while “Coupling between aerobic glycolysis and plasticity by norepinephrine” links increased lactate to memory processing. The copy does not establish that elevated glutamate levels are associated with memory formation, or specifically link the reported elevations to processing incoming sensory stimuli. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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References 88 · Cited by 130

Research works printed but not linked: 68

  1. [1]Vyazovskiy VV Sleep, recovery, and metaregulation: explaining the benefits of sleep Nat Sci Sleep 2015 7 171 184 26719733 PMC4689288
  2. [2]Harris JJ Jolivet R Attwell D Synaptic energy use and supply Neuron 2012 75 762 777 22958818
  3. [4]Wehr TA A brain-warming function for REM sleep Neuroscience & Biobehavioral Reviews 1992 16 379 397 1528526
  4. [5]Vyazovskiy VV Palchykova S Achermann P Tobler I Deboer T Different Effects of Sleep Deprivation and Torpor on EEG Slow-Wave Characteristics in Djungarian Hamsters Cereb Cortex 2017 1 12 PMC5390404 28168294
  5. [7]Dienel GA Cruz NF Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism J Neurochem 2016 138 14 52 27166428
  6. [8]Van den Noort S Brine K Effect of sleep on brain labile phosphates and metabolic rate Am J Physiol 1970 218 1434 1439 4245209
  7. [9]Netchiporouk L Shram N Salvert D Cespuglio R Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake cycle Eur J Neurosci 2001 13 1429 1434 11298804
  8. [10]Dash MB Bellesi M Tononi G Cirelli C Sleep/wake dependent changes in cortical glucose concentrations J Neurochem 2013 124 79 89 23106535 PMC3518620
  9. [12]Clegern WC Moore ME Schmidt MA Wisor J Simultaneous electroencephalography, real-time measurement of lactate concentration and optogenetic manipulation of neuronal activity in the rodent cerebral cortex J Vis Exp 2012 e4328 23271428 PMC3576421
  10. [13]Shram N Netchiporouk L Cespuglio R Lactate in the brain of the freely moving rat: voltammetric monitoring of the changes related to the sleep-wake states Eur J Neurosci 2002 16 461 466 12193189
  11. [14]Rempe MJ Wisor JP Cerebral lactate dynamics across sleep/wake cycles Front Comput Neurosci 2014 8 174 25642184 PMC4294128
  12. [15]Dash MB Tononi G Cirelli C Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex Sleep 2012 35 909 919 22754037 PMC3369226
  13. [16]Richter D Dawson RM Brain metabolism in emotional excitement and in sleep Am J Physiol 1948 154 73 79 18893062
  14. [17]Cespuglio R Netchiporouk L Shram N Glucose and Lactate Monitoring Across the Rat Sleep–Wake Cycle Microelectrode Biosensors Marinesco S Dale N Humana Press 2013 241 256
  15. [18]McNay EC Fries TM Gold PE Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task Proc Natl Acad Sci U S A 2000 97 2881 2885 10706633 PMC16024
  16. [19]Naylor E Aillon DV Gabbert S Harmon H Johnson DA Wilson GS Petillo PA Simultaneous real-time measurement of EEG/EMG and L-glutamate in mice: A biosensor study of neuronal activity during sleep J Electroanal Chem (Lausanne) 2011 656 106 113 27076812 PMC4827928
  17. [20]Dash MB Douglas CL Vyazovskiy VV Cirelli C Tononi G Long-term homeostasis of extracellular glutamate in the rat cerebral cortex across sleep and waking states J Neurosci 2009 29 620 629 19158289 PMC2770705
  18. [21]Dworak M McCarley RW Kim T Kalinchuk AV Basheer R Sleep and brain energy levels: ATP changes during sleep J Neurosci 2010 30 9007 9016 20592221 PMC2917728
  19. [22]Wong-Riley M What is the meaning of the ATP surge during sleep? Sleep 2011 34 833 834 21731129 PMC3119554
  20. [24]Fox PT Raichle ME Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects Proc Natl Acad Sci U S A 1986 83 1140 1144 3485282 PMC323027
  21. [25]Blomqvist G Seitz RJ Sjogren I Halldin C Stone-Elander S Widen L Solin O Haaparanta M Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography Acta Physiol Scand 1994 151 29 43 8048334
  22. [27]Maquet P Dive D Salmon E Sadzot B Franco G Poirrier R von Frenckell R Franck G Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose method Brain Res 1990 513 136 143 2350676
  23. [28]Heiss WD Pawlik G Herholz K Wagner R Wienhard K Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming Brain Res 1985 327 362 366 3872693
  24. [29]Franck G Salmon E Poirrier R Sadzot B Franco G Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography Rev Electroencephalogr Neurophysiol Clin 1987 17 71 77 3495831
  25. [30]Buchsbaum MS Gillin JC Wu J Hazlett E Sicotte N Dupont RM Bunney WE Jr Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography Life Sci 1989 45 1349 1356 2796606
  26. [31]Hoshi Y Mizukami S Tamura M Dynamic features of hemodynamic and metabolic changes in the human brain during all-night sleep as revealed by near-infrared spectroscopy Brain Res 1994 652 257 262 7953738
  27. [32]Mangold R Sokoloff L Conner E Kleinerman J Therman PO Kety SS The effects of sleep and lack of sleep on the cerebral circulation and metabolism of normal young men J Clin Invest 1955 34 1092 1100 14392224 PMC438860
  28. [33]Madsen PL Schmidt JF Holm S Vorstrup S Lassen NA Wildschiodtz G Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2) Brain Res 1991 557 217 220 1747754
  29. [34]Madsen PL Schmidt JF Wildschiodtz G Friberg L Holm S Vorstrup S Lassen NA Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep J Appl Physiol (1985) 1991 70 2597 2601 1885454
  30. [35]Wisor JP Rempe MJ Schmidt MA Moore ME Clegern WC Sleep slow-wave activity regulates cerebral glycolytic metabolism Cereb Cortex 2013 23 1978 1987 22767634 PMC3707408
  31. [37]Sara SJ Locus Coeruleus in time with the making of memories Curr Opin Neurobiol 2015 35 87 94 26241632
  32. [39]Vaishnavi SN Vlassenko AG Rundle MM Snyder AZ Mintun MA Raichle ME Regional aerobic glycolysis in the human brain Proc Natl Acad Sci U S A 2010 107 17757 17762 20837536 PMC2955101
  33. Shannon BJ Vaishnavi SN Vlassenko AG Shimony JS Rutlin J Raichle ME Brain aerobic glycolysis and motor adaptation learning Proc Natl Acad Sci U S A 2016 113 E3782 3791 The first in vivo human study measuring brain glucose/oxygen utilization and plasticity changes during a visual-motor adaptation task. Combining [18F]-fluorodeoxyglucose and [15O]-water/carbon monoxide/oxygen positron-emission tomography with functional-connectivity magnetic resonance imaging, a correlation between increased aerobic glycolysis, resting-state connectivity and behavioral adaptation was reported. These outcomes strongly support a number of recent observations that identied aerobic glycolysis as a critical mechanism for memory formation 27217563 PMC4932971
  34. [42]Newman LA Korol DL Gold PE Lactate produced by glycogenolysis in astrocytes regulates memory processing PLoS One 2011 6 e28427 22180782 PMC3236748
  35. [44]Tadi M Allaman I Lengacher S Grenningloh G Magistretti PJ Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory PLoS One 2015 10 e0141568 26513352 PMC4625956
  36. [45]Yang J Ruchti E Petit JM Jourdain P Grenningloh G Allaman I Magistretti PJ Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons Proc Natl Acad Sci U S A 2014 111 12228 12233 25071212 PMC4143009
  37. [46]Cirelli C Tononi G Differential expression of plasticity-related genes in waking and sleep and their regulation by the noradrenergic system J Neurosci 2000 20 9187 9194 11124996 PMC6773024
  38. [47]Tang F Lane S Korsak A Paton JF Gourine AV Kasparov S Teschemacher AG Lactate-mediated glia-neuronal signalling in the mammalian brain Nat Commun 2014 5 3284 24518663 PMC3926012
  39. Lundgaard I Lu ML Yang E Peng W Mestre H Hitomi E Deane R Nedergaard M Glymphatic clearance controls state-dependent changes in brain lactate concentration J Cereb Blood Flow Metab 2016 37 2112 2124 Role of glymphatic system in brain lactate decrease associated with sleep assessed in mice in vivo. Different procedures known to impair insterstitial-cerebrospinal fluid exchange and glymphatic function were found to abolish the decrease in cerebral lactate as measured by microdialysis. As lymphatic-paravascular fluxes are substantially smaller during wakefulness than sleep, the study suggests that the glymphatic system contributes to maintain waking brain lactate levels 27481936 PMC5464705
  40. [50]Ball KK Cruz NF Mrak RE Dienel GA Trafficking of glucose, lactate, and amyloid-beta from the inferior colliculus through perivascular routes J Cereb Blood Flow Metab 2010 30 162 176 19794399 PMC2801760
  41. [51]DiNuzzo M Astrocyte-Neuron Interactions during Learning May Occur by Lactate Signaling Rather than Metabolism Front Integr Neurosci 2016 10 2 26858613 PMC4731513
  42. [52]O’Donnell J Zeppenfeld D McConnell E Pena S Nedergaard M Norepinephrine: a neuromodulator that boosts the function of multiple cell types to optimize CNS performance Neurochem Res 2012 37 2496 2512 22717696 PMC3548657
  43. [53]Sherpa AD Xiao F Joseph N Aoki C Hrabetova S Activation of beta-adrenergic receptors in rat visual cortex expands astrocytic processes and reduces extracellular space volume Synapse 2016 70 307 316 27085090 PMC4909535
  44. Ding F O’Donnell J Xu Q Kang N Goldman N Nedergaard M Changes in the composition of brain interstitial ions control the sleep-wake cycle Science 2016 352 550 555 In vivo measurements of interstitial fluid ionic composition during sleep-wake cycle in mice. Alterations in the extracellular concentration of several important ions were reported to correlate with sleep and waking in a neuromodulator-dependent manner. Blockade of neuronal activity failed to prevent these changes from occurring during state transitions. Most importantly, topical application or intracisternal injection of artificial cerebrospinal fluid with ion concentrations mimicking sleep and wake states recapitulated the corresponding electrophysiological brain patterns regardless of the actual brain state. The study demonstrates that changes in neuronal discharge associated with sleep and wakefulness are secondary to changes in interstitial ionic levels 27126038 PMC5441687
  45. [55]Baskey G Singh A Sharma R Mallick BN REM sleep deprivation-induced noradrenaline stimulates neuronal and inhibits glial Na-K ATPase in rat brain: in vivo and in vitro studies Neurochem Int 2009 54 65 71 19013490
  46. [56]Risher WC Andrew RD Kirov SA Real-Time Passive Volume Responses of Astrocytes to Acute Osmotic and Ischemic Stress in Cortical Slices and in vivo Revealed by Two-Photon Microscopy Glia 2009 57 207 221 18720409 PMC2635108
  47. [57]Andrew RD Labron MW Boehnke SE Carnduff L Kirov SA Physiological evidence that pyramidal neurons lack functional water channels Cereb Cortex 2007 17 787 802 16723408
  48. Bellesi M de Vivo L Tononi G Cirelli C Effects of sleep and wake on astrocytes: clues from molecular and ultrastructural studies BMC Biol 2015 13 66 Determination of astrocytic gene expression and ultrastructure during sleep-wake cycle. Using a combination of techniques, an association between wakefulness (sleep) and increases (decreases) in elongation, surface area and synaptic coverage of peripheral astrocytic processes was found. The study provides a structural support for state-dependent changes in astrocyte-neuron interactions 26303010 PMC4548305
  49. [59]Wang F Smith NA Xu Q Fujita T Baba A Matsuda T Takano T Bekar L Nedergaard M Astrocytes modulate neural network activity by Ca(2)+-dependent uptake of extracellular K+ Sci Signal 2012 5 ra26 22472648 PMC3515082
  50. [60]Vyazovskiy VV Olcese U Lazimy YM Faraguna U Esser SK Williams JC Cirelli C Tononi G Cortical firing and sleep homeostasis Neuron 2009 63 865 878 19778514 PMC2819325
  51. Watson BO Levenstein D Greene JP Gelinas JN Buzsaki G Network Homeostasis and State Dynamics of Neocortical Sleep Neuron 2016 90 839 852 In vivo measurements of neuronal firing during sleep-wake cycle in rats. By sampling a large number of neurons using multi-site silicon-probe based recordings, sleep sub-stages were reported to be associated with homeostasis of neuronal firing rate distribution (i.e. homogenization). The study suggests that sleep rebalances learning-induced and homeostatic plastic processes 27133462 PMC4873379
  52. [62]Abbott LF Varela JA Sen K Nelson SB Synaptic depression and cortical gain control Science 1997 275 220 224 8985017
  53. [63]Papouin T Dunphy J Tolman M Foley JC Haydon PG Astrocytic control of synaptic function Philos Trans R Soc Lond B Biol Sci 2017 372 PMC5247586 28093548
  54. [65]Hinckelmann M-V Virlogeux A Niehage C Poujol C Choquet D Hoflack B Zala D Saudou F Self-propelling vesicles define glycolysis as the minimal energy machinery for neuronal transport Nature Communications 2016 7 13233 PMC5078996 27775035
  55. [66]Ikemoto A Bole DG Ueda T Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase J Biol Chem 2003 278 5929 5940 12488440
  56. [67]Ishida A Noda Y Ueda T Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake Neurochem Res 2009 34 807 818 18751889 PMC2659335
  57. [68]Zala D Hinckelmann MV Yu H Lyra da Cunha MM Liot G Cordelieres FP Marco S Saudou F Vesicular glycolysis provides on-board energy for fast axonal transport Cell 2013 152 479 491 23374344
  58. [70]Sasaki T Matsuki N Ikegaya Y Action-potential modulation during axonal conduction Science 2011 331 599 601 21292979
  59. [73]Xu J Song D Xue Z Gu L Hertz L Peng L Requirement of Glycogenolysis for Uptake of Increased Extracellular K(+) in Astrocytes: Potential Implications for K (+) Homeostasis and Glycogen Usage in Brain Neurochem Res 2013 38 472 485 23232850
  60. [74]Sickmann HM Walls AB Schousboe A Bouman SD Waagepetersen HS Functional significance of brain glycogen in sustaining glutamatergic neurotransmission J Neurochem 2009 109 Suppl 1 80 86 19393012
  61. [75]Bittner CX Valdebenito R Ruminot I Loaiza A Larenas V Sotelo-Hitschfeld T Moldenhauer H San Martin A Gutierrez R Zambrano M Fast and reversible stimulation of astrocytic glycolysis by K+ and a delayed and persistent effect of glutamate J Neurosci 2011 31 4709 4713 21430169 PMC6622916
  62. [76]Drulis-Fajdasz D Wójtowicz T Wawrzyniak M Wlodarczyk J Mozrzymas JW Rakus D Involvement of cellular metabolism in age-related LTP modifications in rat hippocampal slices Oncotarget 2015 6 14065 14081 26101857 PMC4546452
  63. [77]Satrustegui J Bak LK Fluctuations in Cytosolic Calcium Regulate the Neuronal Malate-Aspartate NADH Shuttle: Implications for Neuronal Energy Metabolism Neurochem Res 2015 40 2425 2430 26138554
  64. [79]Kjaerby C Rasmussen R Andersen M Nedergaard M Does Global Astrocytic Calcium Signaling Participate in Awake Brain State Transitions and Neuronal Circuit Function? Neurochem Res 2017 42 1810 1822 28210958 PMC5451293
  65. [80]Levenstein D Watson BO Rinzel J Buzsaki G Sleep regulation of the distribution of cortical firing rates Curr Opin Neurobiol 2017 44 34 42 28288386 PMC5511069
  66. [81]Turrigiano GG The dialectic of Hebb and homeostasis Philos Trans R Soc Lond B Biol Sci 2017 372 PMC5247594 28093556
  67. Hengen Keith B Torrado Pacheco A McGregor James N Van Hooser Stephen D Turrigiano Gina G Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake Cell 2016 165 180 191 In vivo measurements of neuronal firing during sleep-wake cycle in rats. Using tungsten microelectrode arrays neuronal firing was monitored in primary visual cortex during firing rate rebound after monocular visual deprivation. Sleep was reported to inhibit rather than promote firing rate homeostasis, indicating that changes in absolute neuronal firing require wakefulness 26997481 PMC4809041
  68. [86]Haydon PG Nedergaard M How do astrocytes participate in neural plasticity? Cold Spring Harb Perspect Biol 2014 7 a020438 25502516 PMC4355266

Authors
DiNuzzo, M., & Nedergaard, M.
Affiliations
University of Copenhagen (DK)
Corresponding author
DiNuzzo, Mauro
ORCID
Venue
Current Opinion in Neurobiology
Publisher
Elsevier BV
Published
2017-12
Volume
47
Pages
65-72
ISSN
0959-4388 (ISSN-L)
DOI
10.1016/j.conb.2017.09.010
PMC
PMC5732842
OpenAlex
W2762575841
Cited by
130
References
88
Citations by year
2026: 7 · 2025: 20 · 2024: 19 · 2023: 14 · 2022: 10 · 2021: 24 · 2020: 17 · 2019: 11 · 2018: 8
FWCI
1.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
European Union's Horizon 2020 research and innovation programme (701635)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
brain energy metabolism, sleep-wake cycle, cerebral metabolic rate, aerobic glycolysis, astrocytes, glymphatic system, interstitial fluid, neuromodulators, synaptic plasticity, neuronal discharge patterns, astrocyte-neuron interaction
MeSH terms
Animals, Brain, Humans, Neuroglia, Neurons, Sleep, Wakefulness

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