Abstract
The energy consumption of the brain is derived from the oxidation of glucose. The basal oxygen/glucose ratio (O/G) in the brain is 5.5. While 90% of glucose is oxidised, a small fraction undergoes glycolysis and gives rise to lactate. The difference between the delivery of oxygen and its utilisation is the oxygen extraction fraction (OEF). Although brain regions differ in their energy consumption under basal conditions there is little or no variation in the OEF. On activation there is an increase in energy production and a decrease in the O/G and an increase in lactate. There are various theories about the nature of the changes during the increased energy production; one of these is the astrocyte-neuron-lactate-shuttle theory according to which neurones use lactate rather than glucose for their increased energy production. An understanding of the causal connections between the changes requires the elucidation of their temporal relationships. In the present review the in vivo changes during activation of oxygen, glucose, glycogen and lactate are examined. The evidence suggests that the additional lactate is not used locally as a substrate for neuronal metabolism. It is proposed that the substantial rise in extracellular lactate is not derived from the uptake of synaptically released glutamate but the reuptake of glutamate released from astrocytes. The release of glutamate is the result of the stimulation of metabotropic glutamate receptors on the astrocytic membrane. Various roles have been proposed for the astrocytic glutamate. The lactate resulting from the reuptake of the astrocytic glutamate has no further function and is removed by diffusion or release into the circulation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abi-Saab WM, Maggs DG, Jones T, Jacob R, Srihari V, Thompson J, Kerr D, Leone P, Krystal JH, Spencer DD, During MJ, Sherwin RS (2002) Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. J Cereb Blood Flow Metab 22:271–279
Ackermann RF, Lear JL (1989) Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose. J Cereb Blood Flow Metab 9:774–785
Ames A 3rd (2000) CNS energy metabolism as related to function. Brain Res Brain Res Rev 34:42–68
Ances BM, Buerk DG, Greenberg JH, Detre JA (2001a) Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats. Neurosci Lett 306:106–110
Ances BM, Wilson DF, Greenberg JH, Detre JA (2001b) Dynamic changes in cerebral blood flow, O2 tension, and calculated cerebral metabolic rate of O2 during functional activation using oxygen phosphorescence quenching. J Cereb Blood Flow Metab 21:511–516
Araque A, Perea G (2004) Glial modulation of synaptic transmission in culture. Glia 47:241–248
Araque A, Parpura V, Sanzgiri RP, Haydon PG (1998a) Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur J Neurosci 10:2129–2142
Araque A, Sanzgiri RP, Parpura V, Haydon PG (1998b) Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. J Neurosci 18:6822–6829
Araque A, Parpura V, Sanzgiri RP, Haydon PG (1999a) Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 22:208–215
Araque A, Sanzgiri RP, Parpura V, Haydon PG (1999b) Astrocyte-induced modulation of synaptic transmission. Can J Physiol Pharmacol 77:699–706
Araque A, Li N, Doyle RT, Haydon PG (2000) SNARE protein-dependent glutamate release from astrocytes. J Neurosci 20:666–673
Araque A, Martin ED, Perea G, Arellano JI, Buno W (2002) Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices. J Neurosci 22:2443–2450
Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403–450
Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133–1145
Baker DA, Xi ZX, Shen H, Swanson CJ, Kalivas PW (2002) The origin and neuronal function of in vivo nonsynaptic glutamate. J Neurosci 22:9134–9141
Ball KK, Gandhi G, Thrash J, Cruz NF, Dienel GA (2007) Astrocytic connexin distributions and rapid, extensive dye transfer via gap junctions in the inferior colliculus: Implications for [14C]glucose metabolite trafficking. J Neurosci Res 85:3267–3283
Barbour B (2001) An evaluation of synapse independence. J Neurosci 21:7969–7984
Bell JE, Hume R, Busuttil A, Burchell A (1993) Immunocytochemical detection of the microsomal glucose-6-phosphatase in human brain astrocytes. Neuropathol Appl Neurobiol 19:429–435
Bequet F, Gomez Merino D, Berthelot M, Guezennec CY (2001) Exercise-induced changes in brain glucose and serotonin revealed by microdialysis in rat hippocampus: effect of glucose supplementation. Acta Physiol Scand 173:223–230
Bergersen LH, Gundersen V (2009) Morphological evidence for vesicular glutamate release from astrocytes. Neuroscience 158:260–265
Bernardinelli Y, Magistretti PJ, Chatton JY (2004) Astrocytes generate Na+-mediated metabolic waves. Proc Natl Acad Sci USA 101:14937–14942
Bezzi P, Carmignoto G, Pasti L, Vesce S, Rossi D, Rizzini BL, Pozzan T, Volterra A (1998) Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 391:281–285
Biggs CS, Fowler LJ, Whitton PS, Starr MS (1995) Impulse-dependent and tetrodotoxin-sensitive release of GABA in the rat’s substantia nigra measured by microdialysis. Brain Res 684:172–178
Brennan AM, Connor JA, Shuttleworth CW (2006) NAD(P)H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function. J Cereb Blood Flow Metab 26:1389–1406
Brennan AM, Connor JA, Shuttleworth CW (2007) Modulation of the amplitude of NAD(P)H fluorescence transients after synaptic stimulation. J Neurosci Res 85:3233–3243
Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192
Buxton RB (2001) The elusive initial dip. NeuroImage 13:953–958
Buxton RB, Frank LR (1997) A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. J Cereb Blood Flow Metab 17:64–72
Buzsaki G (2006) Rhythms of the Brain. Oxford University Press, Oxford
Buzsaki G, Draguhn A (2004) Neuronal oscillations in cortical networks. Science 304:1926–1929
Buzsáki G, Kaila K, Raichle M (2007) Inhibition and brain work. Neuron 56:771–783
Caesar K, Hashemi P, Douhou A, Bonvento G, Boutelle MG, Walls AB, Lauritzen M (2008) Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo. J Physiol (Lond) 586:1337–1349
Canal CE, McNay EC, Gold PE (2005) Increases in extracellular fluid glucose levels in the rat hippocampus following an anesthetic dose of pentobarbital or ketamine-xylazine: an in vivo microdialysis study. Physiol Behav 84:245–250
Carmignoto G, Fellin T (2006) Glutamate release from astrocytes as a non-synaptic mechanism for neuronal synchronization in the hippocampus. J Physiol 99:2–3
Chatton JY, Pellerin L, Magistretti PJ (2003) GABA uptake into astrocytes is not associated with significant metabolic cost: implications for brain imaging of inhibitory transmission. Proc Natl Acad Sci USA 100:12456–12461
Chih CP, Roberts EL Jr (2003) Energy substrates for neurons during neural activity: a critical review of the astrocyte-neuron lactate shuttle hypothesis. J Cereb Blood Flow Metab 23:1263–1281
Chih CP, Lipton P, Roberts EL Jr (2001) Do active cerebral neurons really use lactate rather than glucose? Trends Neurosci 24:573–578
Choi IY, Gruetter R (2003) In vivo 13C NMR assessment of brain glycogen concentration and turnover in the awake rat. Neurochem Int 43:317–322
Cholet N, Pellerin L, Welker E, Lacombe P, Seylaz J, Magistretti PJ, Bonvento G (2001) Local injection of antisense oligonucleotides targeted to the glial glutamate transporter GLAST decreases the metabolic response to somatosensory activation. J Cereb Blood Flow Metab 21:404–412
Cohen PJH, Wollman SC, Alexander PE, Behar MG (1964) Cerebral carbohydrate metabolism in man during halothane anaesthesia. Anaesthesiology 25:185–191
Collins RC, McCandless DW, Wagman IL (1987) Cerebral glucose utilization: comparison of [14C]deoxyglucose and [6-14C]glucose quantitative autoradiography. J Neurochem 49:1564–1570
Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith JS (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247:470–473
Cruz NF, Dienel GA (2002) High glycogen levels in brains of rats with minimal environmental stimuli: implications for metabolic contributions of working astrocytes. J Cereb Blood Flow Metab 22:1476–1489
Cruz NF, Ball KK, Dienel GA (2007) Functional imaging of focal brain activation in conscious rats: impact of [(14)C]glucose metabolite spreading and release. J Neurosci Res 85: 3254–3266
Dale AM, Halgren E (2001) Spatiotemporal mapping of brain activity by integration of multiple imaging modalities. Curr Opin Neurobiol 11:202–208
Day BK, Pomerleau F, Burmeister JJ, Huettl P, Gerhardt GA (2006) Microelectrode array studies of basal and potassium-evoked release of L-glutamate in the anesthetized rat brain. J Neurochem 96:1626–1635
Demestre M, Boutelle M, Fillenz M (1997) Stimulated release of lactate in freely moving rats is dependent on the uptake of glutamate. J Physiol 499:825–832
Derouiche A, Frotscher M (2001) Peripheral astrocyte processes: monitoring by selective immunostaining for the actin-binding ERM proteins. Glia 36:330–341
Diamond JS (2001) Neuronal glutamate transporters limit activation of NMDA receptors by neurotransmitter spillover on CA1 pyramidal cells. J Neurosci 21:8328–8338
Diamond JS (2002) A broad view of glutamate spillover. Nat Neurosci 5:291–292
Dienel G (2004a) Glial biology: functional interactions among glia and neurons. Neurochem Int 45:189–190
Dienel GA (2004b) Lactate muscles its way into consciousness: fueling brain activation. Am J Physiol 287:R519–R521
Dienel GA, Cruz NF (2003) Neighborly interactions of metabolically-activated astrocytes in vivo. Neurochem Int 43:339–354
Dienel GA, Cruz NF (2004) Nutrition during brain activation: does cell-to-cell lactate shuttling contribute significantly to sweet and sour food for thought? Neurochem Int 45:321–351
Dienel GA, Hertz L (2001) Glucose and lactate metabolism during brain activation. J Neurosci Res 66:824–838
Dienel GA, Nelson T, Cruz NF, Jay T, Crane AM, Sokoloff L (1988) Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2-3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites. J Biol Chem 263:19697–19708
Dienel GA, Schmidt K, Cruz NF (2007) Astrocyte activation in vivo during graded photic stimulation. J Neurochem 103:1506–1522
Dringen R, Gebhardt R, Hamprecht B (1993) Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res 623:208–214
Duong TQ, Kim DS, Ugurbil K, Kim SG (2000) Spatiotemporal dynamics of the BOLD fMRI signals: toward mapping submillimeter cortical columns using the early negative response. Magnetic Resonance in Medicine 44:231–242
Erecinska M, Silver IA (1989) ATP and brain function. J Cereb Blood Flow Metab 9:2–19
Erecinska M, Silver IA (1994) Ions and energy in mammalian brain. Prog Neurobiol 43:37–71
Fellin T, Pascual O, Haydon PG (2006) Astrocytes coordinate synaptic networks: balanced excitation and inhibition. Physiology 21:208–215
Fellows LK, Boutelle MG, Fillenz M (1992) Extracellular brain glucose levels reflect local neuronal activity: a microdialysis study in awake, freely moving rats. J Neurochem 59:2141–2147
Fellows LK, Boutelle MG, Fillenz M (1993) Physiological stimulation increases nonoxidative glucose metabolism in the brain of the freely moving rat. J Neurochem 60:1258–1263
Fillenz M (2005) The role of lactate in brain metabolism. Neurochem Int 47:413–417
Fillenz M, Lowry JP (1998) Studies of the source of glucose in the extracellular compartment of the rat brain. Dev Neurosci 20:365–368
Forsyth RJ, Bartlett K, Eyre J (1996) Dephosphorylation of 2-deoxyglucose 6-phosphate and 2-deoxyglucose export from cultured astrocytes. Neurochem Int 28:243–250
Foster KA, Beaver CJ, Turner DA (2005) Interaction between tissue oxygen tension and NADH imaging during synaptic stimulation and hypoxia in rat hippocampal slices. Neuroscience 132:645–657
Fox PT, Raichle ME (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci USA 83:1140–1144
Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711
Fox PT, Raichle ME, Mintun MA, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–464
Fray AE, Forsyth RJ, Boutelle MG, Fillenz M (1996) The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study. J Physiol 496:49–57
Fray AE, Boutelle M, Fillenz M (1997) Extracellular glucose turnover in the striatum of unanaesthetized rats measured by quantitative microdialysis. J Physiol 504:721–726
Gadea A, Lopez-Colome AM (2001) Glial transporters for glutamate, glycine, and GABA III. Glycine transporters. J Neurosci Res 64:218–222
Gibbs ME, Anderson DG, Hertz L (2006) Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens. Glia 54:214–222
Gibbs ME, Hutchinson D, Hertz L (2008) Astrocytic involvement in learning and memory consolidation. Neurosci Biobehav Rev 32:927–944
Gjedde A, Marrett S (2001) Glycolysis in neurons, not astrocytes, delays oxidative metabolism of human visual cortex during sustained checkerboard stimulation in vivo. J Cereb Blood Flow Metab 21:1384–1392
Gotoh J, Kuang TY, Nakao Y, Cohen DM, Melzer P, Itoh Y, Pak H, Pettigrew K, Sokoloff L (2001) Regional differences in mechanisms of cerebral circulatory response to neuronal activation. Am J Physiol 280:H821–H829
Gruetter R (2003) Glycogen: the forgotten cerebral energy store. J Neurosci Res 74:179–183
Guionie O, Clottes E, Stafford K, Burchell A (2003) Identification and characterisation of a new human glucose-6-phosphatase isoform. FEBS Lett 551:159–164
Gusnard DA, Raichle ME (2001) Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci 2:685–694
Haydon PG (2001) GLIA: listening and talking to the synapse. Nat Rev Neurosci 2:185–193
Hepp R, Perraut M, Chasserot Golaz S, Galli T, Aunis D, Langley K, Grant NJ (1999) Cultured glial cells express the SNAP-25 analogue SNAP-23. Glia 27:181–187
Herrera-Marschitz M, You ZB, Goiny M, Meana JJ, Silveira R, Godukhin OV, Chen Y, Espinoza S, Pettersson E, Loidl CF, Lubec G, Andersson K, Nylander I, Terenius L, Ungerstedt U (1996) On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis. J Neurochem 66:1726–1735
Hertz L, Peng L, Lai JCK (1998) Functional studies in cultured astrocytes. Methods - A companion to Method Enzymol 16:293–310
Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249
Hirase H, Qian L, Barthó P, Buzsáki G (2004) Calcium dynamics of cortical astrocytic networks in vivo. Plos Biol 2:0494–0499
Hu Y, Wilson GS (1997a) A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor. J Neurochem 69:1484–1490
Hu Y, Wilson GS (1997b) Rapid changes in local extracellular rat brain glucose observed with an in vivo glucose sensor. J Neurochem 68:1745–1752
Huang MT, Veech RL (1986) Glucose-6-phosphatase activity in brain. Science 234:1128–1129
Hyder F, Shulman RG, Rothman DL (1998) A model for the regulation of cerebral oxygen delivery. J Appl Physiol 85:554–564
Innocenti B, Parpura V, Haydon PG (2000) Imaging extracellular waves of glutamate during calcium signaling in cultured astrocytes. J Neurosci 20:1800–1808
Jeftinija SD, Jeftinija KV, Stefanovic G, Liu F (1996) Neuroligand-evoked calcium-dependent release of excitatory amino acids from cultured astrocytes. J Neurochem 66:676–684
Jeremic A, Jeftinija K, Stevanovic J, Glavaski A, Jeftinija S (2001) ATP stimulates calcium-dependent glutamate release from cultured astrocytes. J Neurochem 77:664–675
Jones M, Berwick J, Johnston D, Mayhew J (2001) Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex. NeuroImage 13:1002–1015
Kann O, Kovács R (2007) Mitochondria and neuronal activity. Am J Physiol, Cell Physiol 292:C641–C657
Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW (2004) Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305:99–103
Korf J (2006) Is brain lactate metabolized immediately after neuronal activity through the oxidative pathway? J Cereb Blood Flow Metab 26:1584–1586
Korf J, Gramsbergen JB (2007) Timing of potential and metabolic brain energy. J Neurochem 103:1697–1708
Kullmann DM, Asztely F (1998) Extrasynaptic glutamate spillover in the hippocampus: evidence and implications. Trends Neurosci 21:8–14
Kullmann DM, Asztely F (2000) Spillover and synaptic cross talk mediated by glutamate and GABA in the mammalian brain. Extrasynaptic glutamate spillover in the hippocampus: evidence and implications. Prog Brain Res 125:339–351
Kullmann D, Min M, Asztely F, Rusakov D (1999) Extracellular glutamate diffusion determines the occupancy of glutamate receptors at CA1 synapses in the hippocampus. Philos Trans R Soc Lond, B, Biol Sci 354:395–402
Langemann H, Alessandri B, Mendelowitsch A, Feuerstein T, Landolt H, Gratzl O (2001) Extracellular levels of glucose and lactate measured by quantitative microdialysis in the human brain. Neurol Res 23:531–536
Leegsma-Vogt G, Venema K, Korf J (2003) Evidence for a lactate pool in the rat brain that is not used as an energy supply under normoglycemic conditions. J Cereb Blood Flow Metab 23:933–941
Lennie P (2003) The cost of cortical computation. Curr Biol 13:493–497
Lindauer U, Royl G, Leithner C, Kühl M, Gold L, Gethmann J, Kohl-Bareis M, Villringer A, Dirnagl U (2001) No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation. NeuroImage 13:988–1001
Lönnroth P, Jansson PA, Smith U (1987) A microdialysis method allowing characterization of interecellular water space in humans. Am J Physiol 253:652–654
Lowry JP, Fillenz M (1997) Evidence for uncoupling of oxygen and glucose utilization during neuronal activation in rat striatum. J Physiol 498:497–501
Lowry JP, Demestre M, Fillenz M (1998a) Relation between cerebral blood flow and extracellular glucose in rat striatum during mild hypoxia and hyperoxia. Dev Neurosci 20:52–58
Lowry JP, O’Neill RD, Boutelle MG, Fillenz M (1998b) Continuous monitoring of extracellular glucose concentrations in the striatum of freely moving rats with an implanted glucose biosensor. J Neurochem 70:391–396
Madsen PL, Linde R, Hasselbalch SG, Paulson OB, Lassen NA (1998) Activation-induced resetting of cerebral oxygen and glucose uptake in the rat. J Cereb Blood Flow Metab 18:742–748
Madsen PL, Cruz NF, Sokoloff L, Dienel GA (1999) Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue. J Cereb Blood Flow Metab 19:393–400
Magistretti PJ, Pellerin L (1999) Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond, B, Biol Sci 354:1155–1163
Magistretti PJ, Pellerin L, Rothman DL, Shulman RG (1999) Energy on demand. Science 283: 496–497
Malarkey EB, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52:142–154
Mangia S, Garreffa G, Bianciardi M, Giove F, Di Salle F, Maraviglia B (2003) The aerobic brain: lactate decrease at the onset of neural activity. Neuroscience 118:7–10
Marcaggi P, Attwell D (2004) Role of glial amino acid transporters in synaptic transmission and brain energetics. Glia 47:217–225
Marota JJ, Ayata C, Moskowitz MA, Weisskoff RM, Rosen BR, Mandeville JB (1999) Investigation of the early response to rat forepaw stimulation. Magn Reson Med 41:247–252
Masamoto K, Omura T, Takizawa N, Kobayashi H, Katura T, Maki A, Kawaguchi H, Tanishita K (2003) Biphasic changes in tissue partial pressure of oxygen closely related to localized neural activity in guinea pig auditory cortex. J Cereb Blood Flow Metab 23:1075–1084
Masamoto K, Vazquez A, Wang P, Kim SG (2009) Brain tissue oxygen consumption and supply induced by neural activation: determined under suppressed hemodynamic response conditions in the anesthetized rat cerebral cortex. Adv Exp Med Biol 645:287–292
Mason GF, Gruetter R, Rothman DL, Behar KL, Shulman RG, Novotny EJ (1995) Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J Cereb Blood Flow Metab 15:12–25
Mayhew J, Johnston D, Berwick J, Jones M, Coffey P, Zheng Y (2000) Spectroscopic analysis of neural activity in brain: increased oxygen consumption following activation of barrel cortex. NeuroImage 12:664–675
McNay EC, Gold PE (1999) Extracellular glucose concentrations in the rat hippocampus measured by zero-net-flux: effects of microdialysis flow rate, strain, and age. J Neurochem 72:785–790
McNay EC, Fries TM, Gold PE (2000) Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task. Proc Natl Acad Sci USA 97:2881–2885
McNay EC, McCarty RC, Gold PE (2001) Fluctuations in brain glucose concentration during behavioral testing: dissociations between brain areas and between brain and blood. Neurobiol Learn Mem 75:325–337
Middleditch C, Marcolongo P, Benedetti A, Burchell A (1997) Glucose-6-phosphatase activity: a determinant of brain microsomal intactness. Biochem Soc Trans 25:183S
Miele M, Berners M, Boutelle MG, Kusakabe H, Fillenz M (1996a) The determination of the extracellular concentration of brain glutamate using quantitative microdialysis. Brain Res 707:131–133
Miele M, Boutelle MG, Fillenz M (1996b) The source of physiologically stimulated glutamate efflux from the striatum of conscious rats. J Physiol 497:745–751
Moghaddam B (1993) Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: comparison to hippocampus and basal ganglia. J Neurochem 60:1650–1657
Montana V, Malarkey EB, Verderio C, Matteoli M, Parpura V (2006) Vesicular transmitter release from astrocytes. Glia 54:700–715
Muyderman H, Angehagen M, Sandberg M, Bjorklund U, Olsson T, Hansson E, Nilsson M (2001) Alpha 1-adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes. J Biol Chem 276:46504–46514
Ndubuizu O, LaManna JC (2007) Brain tissue oxygen concentration measurements. Antioxid Redox Signal 9:1207–1219
Nehlig A, Coles J (2007) Cellular pathways of energy metabolism in the brain: is glucose used by neurons or astrocytes? Glia 55:1238–1250
Nehlig A, Wittendorp-Rechenmann E, Lam CD (2004) Selective uptake of [14C]2-deoxyglucose by neurons and astrocytes: high-resolution microautoradiographic imaging by cellular 14C-trajectography combined with immunohistochemistry. J Cereb Blood Flow Metab 24:1004–1014
Netchiporouk L, Shram N, Salvert D, Cespuglio R (2001) Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake cycle. Eur J Neurosci 13:1429–1434
Newman EA, Volterra A (2004) Glial control of synaptic function. Glia 47:207–208
Ni Y, Malarkey E, Parpura V (2007) Vesicular release of glutamate mediates bidirectional signaling between astrocytes and neurons. J Neurochem 103:1273–1284
Offenhauser N, Thomsen K, Caesar K, Lauritzen M (2005) Activity-induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activation and blood flow. J Physiol 565:279–294
Olson RJ, Justice JB Jr (1993) Quantitative microdialysis under transient conditions. Anal Chem 65:1017–1022
Osborne PG, Niwa O, Kato T, Yamamoto K (1997) On-line, continuous measurement of extracellular striatal glucose using microdialysis sampling and electrochemical detection. J Neurosci Methods 77:143–150
Parpura V, Scemes E, Spray DC (2004) Mechanisms of glutamate release from astrocytes: gap junction “hemichannels”, purinergic receptors and exocytotic release. Neurochem Int 45:259–264
Pasti L, Volterra A, Pozzan T, Carmignoto G (1997) Intracellular calcium oscillations in astrocytes: a highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J Neurosci 17:7817–7830
Pasti L, Zonta M, Pozzan T, Vicini S, Carmignoto G (2001) Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate. J Neurosci 21:477–484
Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL (2005) The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci USA 102:5588–5593
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91: 10625–10629
Pellerin L, Magistretti PJ (1996) Excitatory amino acids stimulate aerobic glycolysis in astrocytes via an activation of the Na+/K + ATPase. Dev Neurosci 18:336–342
Pellerin L, Magistretti PJ (1997) Glutamate uptake stimulates Na+, K + -ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 69: 2132–2137
Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, Stella N, Magistretti PJ (1998) Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 20:291–299
Pfeiffer B, Meyermann R, Hamprecht B (1992) Immunohistochemical co-localization of glycogen phosphorylase with the astroglial markers glial fibrillary acidic protein and S-100 protein in rat brain sections. Histochemistry 97:405–412
Piet R, Vargová L, Syková E, Poulain DA, Oliet SH (2004) Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk. Proc Natl Acad Sci USA 101:2151–2155
Porter JT, McCarthy KD (1996) Hippocampal astrocytes in situ respond to glutamate released from synaptic terminals. J Neurosci 16:5073–5081
Prichard J, Rothman D, Novotny E, Petroff O, Kuwabara T, Avison M, Howseman A, Hanstock C, Shulman R (1991) Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc Natl Acad Sci USA 88:5829–5831
Raichle ME (1998) Behind the scenes of functional brain imaging: a historical and physiological perspective. Proc Natl Acad Sci USA 95:765–772
Raichle ME (2001) Cognitive neuroscience. Bold insights. Nature 412:128–130
Raichle M, Snyder AZ (2007) A default mode of brain function: a brief history of an evolving idea. NeuroImage 37:1083–1090
Reinstrup P, Ståhl N, Mellergård P, Uski T, Ungerstedt U, Nordström CH (2000) Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery. Neurosurgery 47:701–710
Ros J, Pecinska N, Alessandri B, Landolt H, Fillenz M (2001) Lactate reduces glutamate-induced neurotoxicity in rat cortex. J Neurosci Res 66:790–794
Roy CS, Sherrington CS (1890) On the regulation of the blood supply of the brain. J Physiol 11:85–108
Rusakov DA (2001) The role of perisynaptic glial sheaths in glutamate spillover and extracellular Ca(2+) depletion. Biophys J 81:1947–1959
Santello M, Volterra A (2008) Synaptic modulation by astrocytes via Ca(2+)-dependent glutamate release. Neuroscience 22(1):253
Sappey-Marinier D, Calabrese G, Fein G, Hugg JW, Biggins C, Weiner MW (1992) Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy. J Cereb Blood Flow Metab 12:584–592
Scemes E, Giaume C (2006) Astrocyte calcium waves: what they are and what they do. Glia 54:716–725
Schasfoort EM, De Bruin LA, Korf J (1988) Mild stress stimulates rat hippocampal glucose utilization transiently via NMDA receptors, as assessed by lactography. Brain Res 475:58–63
Schmalbruch IK, Linde R, Paulson OB, Madsen PL (2002) Activation-induced resetting of cerebral metabolism and flow is abolished by beta-adrenergic blockade with propranolol. Stroke 33:251–255
Schurr A (2006) Lactate: the ultimate cerebral oxidative energy substrate? J Cereb Blood Flow Metab 26:142–152
Schurr A, Payne RS (2007) Lactate, not pyruvate, is neuronal aerobic glycolysis end product: an in vitro electrophysiological study. Neuroscience 147:613–619
Segal M, Greenberger V, Hofstein R (1981) Cyclic AMP-generating systems in rat hippocampal slices. Brain Res 213:351–364
Shelton MK, McCarthy KD (2000) Hippocampal astrocytes exhibit Ca2+ -elevating muscarinic cholinergic and histaminergic receptors in situ. J Neurochem 74:555–563
Shulman RG, Hyder F, Rothman DL (2001a) Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Natl Acad Sci USA 98:6417–6422
Shulman RG, Hyder F, Rothman DL (2001b) Lactate efflux and the neuroenergetic basis of brain function. NMR Biomed 14:389–396
Shuttleworth CW, Brennan AM, Connor JA (2003) NAD(P)H fluorescence imaging of postsynaptic neuronal activation in murine hippocampal slices. J Neurosci 23:3196–3208
Sibson NR, Dhankhar A, Mason GF, Behar KL, Rothman DL, Shulman RG (1997) In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc Natl Acad Sci USA 94:2699–2704
Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL, Shulman RG (1998) Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci USA 95:316–321
Siesjö BK (1978) Brain Energy Metabolism. John Wiley & Sons, Chichester
Silva AC, Lee SP, Yang G, Iadecola C, Kim SG (1999) Simultaneous blood oxygenation level-dependent and cerebral blood flow functional magnetic resonance imaging during forepaw stimulation in the rat. J Cereb Blood Flow Metab 19:871–879
Silver IA, Erecinska M (1994) Extracellular glucose concentration in mammalian brain: continuous monitoring of changes during increased neuronal activity and upon limitation in oxygen supply in normo-, hypo-, and hyperglycemic animals. J Neurosci 14:5068–5076
Silver IA, Erecinska M (1997) Energetic demands of the Na+/K + ATPase in mammalian astrocytes. Glia 21:35–45
Smith AD, Olson RJ, Justice JB Jr (1992) Quantitative microdialysis of dopamine in the striatum: effect of circadian variation. J Neurosci Methods 44:33–41
Sokoloff L (1980) Local cerebral energy metabolism: its relationship to local functional activity and blood flow. Bull Schweiz Akad Med Wiss 36:71–91
Sokoloff L (1981) The deoxyglucose method for the measurement of local glucose utilization and the mapping of local functional activity in the central nervous system. Int Rev Neurobiol 22:287–333
Sorg O, Magistretti PJ (1991) Characterization of the glycogenolysis elicited by vasoactive intestinal peptide, noradrenaline and adenosine in primary cultures of mouse cerebral cortical astrocytes. Brain Res 563:227–233
Sporn J, Molinoff P (1976) beta-Adrenergic receptors in rat brain. J Cyclic Nucleotide Res 2:149–161
Swanson RA, Morton MM, Sagar SM, Sharp FR (1992) Sensory stimulation induces local cerebral glycogenolysis: demonstration by autoradiography. Neuroscience 51:451–461
Thompson JK, Peterson MR, Freeman RD (2003) Single-neuron activity and tissue oxygenation in the cerebral cortex. Science 299:1070–1072
Timmerman W, Westerink BH (1997) Brain microdialysis of GABA and glutamate: what does it signify? Synapse 27:242–261
Tsacopoulos M, Magistretti PJ (1996) Metabolic coupling between glia and neurons. J Neurosci 16:877–885
Vafaee MS, Gjedde A (2000) Model of blood-brain transfer of oxygen explains nonlinear flow-metabolism coupling during stimulation of visual cortex. J Cereb Blood Flow Metab 20:747–754
van der Kuil JH, Korf J (1991) On-line monitoring of extracellular brain glucose using microdialysis and a NADPH-linked enzymatic assay. J Neurochem 57:648–654
Vanzetta I, Grinvald A (1999) Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. Science 286:1555–1558
Vanzetta I, Grinvald A (2001) Evidence and lack of evidence for the initial dip in the anesthetized rat: implications for human functional brain imaging. NeuroImage 13:959–967
Vazquez AL, Masamoto K, Kim SG (2008) Dynamics of oxygen delivery and consumption during evoked neural stimulation using a compartment model and CBF and tissue P(O2) measurements. NeuroImage 42:49–59
Ventura R, Harris KM (1999) Three-dimensional relationships between hippocampal synapses and astrocytes. J Neurosci 19:6897–6906
Verkhratsky A, Kettenmann H (1996) Calcium signalling in glial cells. Trends Neurosci 19:346–352
Vincent JL, Patel GH, Fox MD, Snyder AZ, Baker JT, Van Essen DC, Zempel JM, Snyder LH, Corbetta M, Raichle ME (2007) Intrinsic functional architecture in the anaesthetized monkey brain. Nature 447:83–86
Volterra A, Steinhauser C (2004) Glial modulation of synaptic transmission in the hippocampus. Glia 47:249–257
Waldfogel D, van Gelderen P, Muellbacher W, Ziemann U, Immisch I, Hallett M (2000) The relative metabolic demand of inhibition and excitation. Nature 406:995–998
Wang X, Lou N, Xu Q, Tian GF, Peng W, Han X, Kang J, Takano T, Nedergaard M (2006) Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo. Nat Neurosci 9:816–823
Watanabe H, Passonneau JV (1973) Factors affecting the turnover of cerebral glycogen and limit dextrin in vivo. J Neurochem 20:1543–1554
Wittendorp-Rechenmann E, Lam CD, Steibel J, Lasbennes F, Nehlig A (2002) High resolution tracer targeting combining microautoradiographic imaging by cellular C-14-trajectography with immunohistochemistry: A novel protocol to demonstrate metabolism of C-14 2-deoxyglucose by neurons and astrocytes. J Trace Microprobe Tech 20:505–515
Yacoub E, Le TH, Ugurbil K, Hu X (1999) Further evaluation of the initial negative response in functional magnetic resonance imaging. Magn Reson Med 41:436–441
Yacoub E, Shmuel A, Pfeuffer J, Van De Moortele PF, Adriany G, Ugurbil K, Hu X (2001) Investigation of the initial dip in fMRI at 7 Tesla. NMR Biomed 14:408–412
Zhang Q, Haydon PG (2005) Roles for gliotransmission in the nervous system. J Neural Transm 112:121–125
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Fillenz, M. (2012). Glucose Metabolism During Neural Activation. In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_21
Download citation
DOI: https://doi.org/10.1007/978-1-4614-1788-0_21
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-1787-3
Online ISBN: 978-1-4614-1788-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)