Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation

Ainscow, 2002, Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(+) channels, J. Physiol., 544, 429, 10.1113/jphysiol.2002.022434 Allaman, 2010, Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability, J. Neurosci., 30, 3326, 10.1523/JNEUROSCI.5098-09.2010 Allaman, 2011, Astrocyte-neuron metabolic relationships: for better and for worse, Trends Neurosci., 34, 76, 10.1016/j.tins.2010.12.001 Alle, 2009, Energy-efficient action potentials in hippocampal mossy fibers, Science, 325, 1405, 10.1126/science.1174331 Almeida, 2001, Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection, Proc. Natl. Acad. Sci. USA, 98, 15294, 10.1073/pnas.261560998 Almeida, 2004, Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway, Nat. Cell Biol., 6, 45, 10.1038/ncb1080 Ances, 2001, Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats, Neurosci. Lett., 306, 106, 10.1016/S0304-3940(01)01868-7 Attwell, 2001, An energy budget for signaling in the grey matter of the brain, J. Cereb. Blood Flow Metab., 21, 1133, 10.1097/00004647-200110000-00001 Attwell, 2010, Glial and neuronal control of brain blood flow, Nature, 468, 232, 10.1038/nature09613 Bak, 2006, The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer, J. Neurochem., 98, 641, 10.1111/j.1471-4159.2006.03913.x Barros, 2010, Glucose and lactate supply to the synapse, Brain Res. Brain Res. Rev., 63, 149, 10.1016/j.brainresrev.2009.10.002 Barros, 2009, Preferential transport and metabolism of glucose in Bergmann glia over Purkinje cells: a multiphoton study of cerebellar slices, Glia, 57, 962, 10.1002/glia.20820 Belanger, 2009, The role of astroglia in neuroprotection, Dialogues Clin. Neurosci., 11, 281, 10.31887/DCNS.2009.11.3/mbelanger Ben Yoseph, 1996, Assessment of the role of the glutathione and pentose phosphate pathways in the protection of primary cerebrocortical cultures from oxidative stress, J. Neurochem., 66, 2329, 10.1046/j.1471-4159.1996.66062329.x Berkich, 2007, Mitochondrial transport proteins of the brain, J. Neurosci. Res., 85, 3367, 10.1002/jnr.21500 Bernardinelli, 2004, Astrocytes generate Na+-mediated metabolic waves, Proc. Natl. Acad. Sci. USA, 101, 14937, 10.1073/pnas.0405315101 Bittner, 2010, High resolution measurement of the glycolytic rate, Front Neuroenergetics., 2, 26, 10.3389/fnene.2010.00026 Bolanos, 2010, Glycolysis: a bioenergetic or a survival pathway?, Trends Biochem. Sci., 35, 145, 10.1016/j.tibs.2009.10.006 Boumezbeur, 2010, Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy, J. Cereb. Blood Flow Metab., 30, 211, 10.1038/jcbfm.2009.197 Boumezbeur, 2010, The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy, J. Neurosci., 30, 13983, 10.1523/JNEUROSCI.2040-10.2010 Bouzier, 2000, The metabolism of [3-(13)C]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment, J. Neurochem., 75, 480, 10.1046/j.1471-4159.2000.0750480.x Bouzier-Sore, 2006, Competition between glucose and lactate as oxidative energy substrates in both neurons and astrocytes: a comparative NMR study, Eur. J. Neurosci., 24, 1687, 10.1111/j.1460-9568.2006.05056.x Brooks, 2009, Cell-cell and intracellular lactate shuttles, J. Physiol., 587, 5591, 10.1113/jphysiol.2009.178350 Brown, 2004, Brain glycogen re-awakened, J. Neurochem., 89, 537, 10.1111/j.1471-4159.2004.02421.x Brown, 2007, Astrocyte glycogen and brain energy metabolism, Glia, 55, 1263, 10.1002/glia.20557 Brown, 2005, Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter, J. Neurosci. Res., 79, 74, 10.1002/jnr.20335 Cahoy, 2008, A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function, J. Neurosci., 28, 264, 10.1523/JNEUROSCI.4178-07.2008 Carmignoto, 2010, The contribution of astrocyte signalling to neurovascular coupling, Brain Res. Brain Res. Rev., 63, 138, 10.1016/j.brainresrev.2009.11.007 Castro, 2009, A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid, J. Neurochem., 110, 423, 10.1111/j.1471-4159.2009.06151.x Cerdan, 2006, The redox switch/redox coupling hypothesis, Neurochem. Int., 48, 523, 10.1016/j.neuint.2005.12.036 Chen, 2001, Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism, J. Neurochem., 77, 1601, 10.1046/j.1471-4159.2001.00374.x Chih, 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, 10.1097/01.WCB.0000081369.51727.6F Cholet, 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, 10.1097/00004647-200104000-00009 Chuquet, 2010, Predominant enhancement of glucose uptake in astrocytes versus neurons during activation of the somatosensory cortex, J. Neurosci., 30, 15298, 10.1523/JNEUROSCI.0762-10.2010 Clarke, 1999, Circulation and energy metabolism of the brain, 637 Dienel, 2007, A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover, J. Neurochem., 102, 466, 10.1111/j.1471-4159.2007.04595.x DiNuzzo, 2010, Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics: evidence from mathematical modeling, J. Cereb. Blood Flow Metab., 30, 586, 10.1038/jcbfm.2009.232 Dringen, 2000, Metabolism and functions of glutathione in brain, Prog. Neurobiol., 62, 649, 10.1016/S0301-0082(99)00060-X Dringen, 1993, Glycogen in astrocytes: possible function as lactate supply for neighboring cells, Brain Res., 623, 208, 10.1016/0006-8993(93)91429-V Erlichman, 2008, Inhibition of Monocarboxylate Transporter 2 in the retrotrapezoid nucleus in rats: a test of the astrocyte-neuron lactate-shuttle hypothesis, J. Neurosci., 28, 4888, 10.1523/JNEUROSCI.5430-07.2008 Figley, 2011, The role(s) of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals, Eur. J. Neurosci., 33, 577, 10.1111/j.1460-9568.2010.07584.x Fox, 1986, Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects, Proc. Natl. Acad. Sci. USA, 83, 1140, 10.1073/pnas.83.4.1140 Fox, 1988, Nonoxidative glucose consumption during focal physiologic neural activity, Science, 241, 462, 10.1126/science.3260686 Gallagher, 2009, The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study, Brain, 132, 2839, 10.1093/brain/awp202 Garcia-Nogales, 2003, Peroxynitrite protects neurons against nitric oxide-mediated apoptosis. A key role for glucose-6-phosphate dehydrogenase activity in neuroprotection, J. Biol. Chem., 278, 864, 10.1074/jbc.M206835200 Genoud, 2006, Plasticity of astrocytic coverage and glutamate transporter expression in adult mouse cortex, PLoS Biol., 4, e343, 10.1371/journal.pbio.0040343 Giaume, 2010, Astroglial networks: a step further in neuroglial and gliovascular interactions, Nat. Rev. Neurosci., 11, 87, 10.1038/nrn2757 Gibbs, 2006, Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens, Glia, 54, 214, 10.1002/glia.20377 Gordon, 2008, Brain metabolism dictates the polarity of astrocyte control over arterioles, Nature, 456, 745, 10.1038/nature07525 Gusnard, 2001, Searching for a baseline: functional imaging and the resting human brain, Nat. Rev. Neurosci., 2, 685, 10.1038/35094500 Halassa, 2007, Synaptic islands defined by the territory of a single astrocyte, J. Neurosci., 27, 6473, 10.1523/JNEUROSCI.1419-07.2007 Halim, 2010, Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons, Glia, 58, 1168, 10.1002/glia.20996 Hashimoto, 2008, Evidence for the mitochondrial lactate oxidation complex in rat neurons: demonstration of an essential component of brain lactate shuttles, PLoS ONE, 3, e2915, 10.1371/journal.pone.0002915 Herard, 2005, Decreased metabolic response to visual stimulation in the superior colliculus of mice lacking the glial glutamate transporter GLT-1, Eur. J. Neurosci., 22, 1807, 10.1111/j.1460-9568.2005.04346.x Herrero-Mendez, 2009, The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1, Nat. Cell Biol., 11, 747, 10.1038/ncb1881 Hu, 1997, 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, 10.1046/j.1471-4159.1997.69041484.x Hyder, 2006, Neuronal-glial glucose oxidation and glutamatergic-GABAergic function, J. Cereb. Blood Flow Metab., 26, 865, 10.1038/sj.jcbfm.9600263 Iadecola, 2007, Glial regulation of the cerebral microvasculature, Nat. Neurosci., 10, 1369, 10.1038/nn2003 Itoh, 2003, Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo, Proc. Natl. Acad. Sci. USA, 100, 4879, 10.1073/pnas.0831078100 Jolivet, 2010, Comment on recent modeling studies of astrocyte-neuron metabolic interactions, J. Cereb. Blood Flow Metab., 30, 1982, 10.1038/jcbfm.2010.132 Kacem, 1998, Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study, Glia, 23, 1, 10.1002/(SICI)1098-1136(199805)23:1<1::AID-GLIA1>3.0.CO;2-B Kasischke, 2004, Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis, Science, 305, 99, 10.1126/science.1096485 Kasischke, 2011, Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions, J. Cereb. Blood Flow Metab., 31, 68, 10.1038/jcbfm.2010.158 Lam, 2005, Regulation of blood glucose by hypothalamic pyruvate metabolism, Science, 309, 943, 10.1126/science.1112085 Lam, 2009, CNS regulation of glucose homeostasis, Physiology (Bethesda), 24, 159, 10.1152/physiol.00003.2009 Laughton, 2007, Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase, BMC Neurosci., 8, 35, 10.1186/1471-2202-8-35 Lebon, 2002, Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism, J. Neurosci., 22, 1523, 10.1523/JNEUROSCI.22-05-01523.2002 Lin, 2010, Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex, Proc. Natl. Acad. Sci. USA, 107, 8446, 10.1073/pnas.0909711107 Lovatt, 2007, The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex, J. Neurosci., 27, 12255, 10.1523/JNEUROSCI.3404-07.2007 Magistretti, 2008, Brain energy metabolism, 271 Magistretti, 2009, Role of glutamate in neuron-glia metabolic coupling, Am. J. Clin. Nutr., 90, 875S, 10.3945/ajcn.2009.27462CC Magistretti, 2005, Relationship between L-glutamate-regulated intracellular Na+ dynamics and ATP hydrolysis in astrocytes, J. Neural Transm., 112, 77, 10.1007/s00702-004-0171-6 Magistretti, 1996, Cellular bases of brain energy metabolism and their relevance to functional brain imaging: evidence for a prominent role of astrocytes, Cereb. Cortex, 6, 50, 10.1093/cercor/6.1.50 Magistretti, 1981, Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism, Proc. Natl. Acad. Sci. USA, 78, 6535, 10.1073/pnas.78.10.6535 Magistretti, 1983, Functional receptors for vasoactive intestinal polypeptide in cultured astroglia from neonatal rat brain, Regul. Pept., 6, 71, 10.1016/0167-0115(83)90136-2 Magistretti, 1993, Regulation of glycogen metabolism in astrocytes: physiological, pharmacological, and pathological aspects, 243 Mangia, 2003, The aerobic brain: lactate decrease at the onset of neural activity, Neuroscience, 118, 7, 10.1016/S0306-4522(02)00792-3 Mangia, 2009, The in vivo neuron-to-astrocyte lactate shuttle in human brain: evidence from modeling of measured lactate levels during visual stimulation, J. Neurochem., 109, 55, 10.1111/j.1471-4159.2009.06003.x McKenna, 2007, The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain, J. Neurosci. Res., 85, 3347, 10.1002/jnr.21444 Metea, 2006, Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling, J. Neurosci., 26, 2862, 10.1523/JNEUROSCI.4048-05.2006 Mosconi, 2008, Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer's disease, Ann. N Y Acad. Sci., 1147, 180, 10.1196/annals.1427.007 Mozrzymas, 2011, The effect of glycogen phosphorolysis on basal glutaminergic transmission, Biochem. Biophys. Res. Commun., 404, 652, 10.1016/j.bbrc.2010.12.033 Mulligan, 2004, Calcium transients in astrocyte endfeet cause cerebrovascular constrictions, Nature, 431, 195, 10.1038/nature02827 Nedergaard, 2003, New roles for astrocytes: redefining the functional architecture of the brain, Trends Neurosci., 26, 523, 10.1016/j.tins.2003.08.008 Nehlig, 2004, Brain uptake and metabolism of ketone bodies in animal models, Prostaglandins Leukot. Essent. Fatty Acids, 70, 265, 10.1016/j.plefa.2003.07.006 Nehlig, 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, 10.1097/01.WCB.0000128533.84196.D8 Oberheim, 2006, Astrocytic complexity distinguishes the human brain, Trends Neurosci., 29, 547, 10.1016/j.tins.2006.08.004 Oberheim, 2009, Uniquely hominid features of adult human astrocytes, J. Neurosci., 29, 3276, 10.1523/JNEUROSCI.4707-08.2009 Offenhauser, 2005, Activity-induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activation and blood flow, J. Physiol., 565, 279, 10.1113/jphysiol.2005.082776 Ogawa, 1992, Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging, Proc. Natl. Acad. Sci. USA, 89, 5951, 10.1073/pnas.89.13.5951 Parsons, 2010, ATP-sensitive potassium channel-mediated lactate effect on orexin neurons: implications for brain energetics during arousal, J. Neurosci., 30, 8061, 10.1523/JNEUROSCI.5741-09.2010 Pellerin, 1994, Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization, Proc. Natl. Acad. Sci. USA, 91, 10625, 10.1073/pnas.91.22.10625 Pellerin, 2007, Activity-dependent regulation of energy metabolism by astrocytes: an update, Glia, 55, 1251, 10.1002/glia.20528 Porras, 2004, Glutamate mediates acute glucose transport inhibition in hippocampal neurons, J. Neurosci., 24, 9669, 10.1523/JNEUROSCI.1882-04.2004 Prichard, 1991, Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation, Proc. Natl. Acad. Sci. USA, 88, 5829, 10.1073/pnas.88.13.5829 Qu, 2000, (13)C MR spectroscopy study of lactate as substrate for rat brain, Dev. Neurosci., 22, 429, 10.1159/000017472 Raichle, 2006, Brain work and brain imaging, Annu. Rev. Neurosci., 29, 449, 10.1146/annurev.neuro.29.051605.112819 Ramos, 2003, Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord, Brain Res. Dev. Brain Res., 143, 33, 10.1016/S0165-3806(03)00097-X Rouach, 2008, Astroglial metabolic networks sustain hippocampal synaptic transmission, Science, 322, 1551, 10.1126/science.1164022 Schmidt, 2008, Neuronal functions, feeding behavior, and energy balance in Slc2a3+/− mice, Am. J. Physiol. Endocrinol. Metab., 295, E1084, 10.1152/ajpendo.90491.2008 Schurr, 2007, Lactate, not pyruvate, is neuronal aerobic glycolysis end product: an in vitro electrophysiological study, Neuroscience, 147, 613, 10.1016/j.neuroscience.2007.05.002 Schurr, 1997, Brain lactate is an obligatory aerobic energy substrate for functional recovery after hypoxia: further in vitro validation, J. Neurochem., 69, 423, 10.1046/j.1471-4159.1997.69010423.x Schurr, 1999, An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons, J. Neurosci., 19, 34, 10.1523/JNEUROSCI.19-01-00034.1999 Serres, 2005, Ex vivo NMR study of lactate metabolism in rat brain under various depressed states, J. Neurosci. Res., 79, 19, 10.1002/jnr.20277 Shih, 2003, Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress, J. Neurosci., 23, 3394, 10.1523/JNEUROSCI.23-08-03394.2003 Shimizu, 2007, Glial Na(x) channels control lactate signaling to neurons for brain [Na+] sensing, Neuron, 54, 59, 10.1016/j.neuron.2007.03.014 Shulman, 2004, Energetic basis of brain activity: implications for neuroimaging, Trends Neurosci., 27, 489, 10.1016/j.tins.2004.06.005 Sibson, 1998, Functional energy metabolism: in vivo 13C-NMR spectroscopy evidence for coupling of cerebral glucose consumption and glutamatergic neuronal activity, Dev. Neurosci., 20, 321, 10.1159/000017327 Sickmann, 2009, Functional significance of brain glycogen in sustaining glutamatergic neurotransmission, J. Neurochem., 109, 80, 10.1111/j.1471-4159.2009.05915.x Simpson, 2007, Supply and demand in cerebral energy metabolism: the role of nutrient transporters, J. Cereb. Blood Flow Metab., 27, 1766, 10.1038/sj.jcbfm.9600521 Smith, 2003, Lactate: a preferred fuel for human brain metabolism in vivo, J. Cereb. Blood Flow Metab., 23, 658, 10.1097/01.WCB.0000063991.19746.11 Sokoloff, 1977, The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat, J. Neurochem., 28, 897, 10.1111/j.1471-4159.1977.tb10649.x Stuart, 2011, Brain glucose transporter (Glut3) haploinsufficiency does not impair mouse brain glucose uptake, Brain Res., 1384, 15, 10.1016/j.brainres.2011.02.014 Suzuki, 2011, Astrocyte-neuron lactate transport is required for long-term memory formation, Cell, 144, 810, 10.1016/j.cell.2011.02.018 Swanson, 1992, Sensory stimulation induces local cerebral glycogenolysis: demonstration by autoradiography, Neuroscience, 51, 451, 10.1016/0306-4522(92)90329-Z Takano, 2006, Astrocyte-mediated control of cerebral blood flow, Nat. Neurosci., 9, 260, 10.1038/nn1623 Tarasov, 2004, Metabolic regulation of the pancreatic beta-cell ATP-sensitive K+ channel: a pas de deux, Diabetes, 53, S113, 10.2337/diabetes.53.suppl_3.S113 Tekkok, 2005, Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity, J. Neurosci. Res., 81, 644, 10.1002/jnr.20573 Tsujino, 2009, Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system, Pharmacol. Rev., 61, 162, 10.1124/pr.109.001321 van Hall, 2009, Blood lactate is an important energy source for the human brain, J. Cereb. Blood Flow Metab., 29, 1121, 10.1038/jcbfm.2009.35 Vargas, 2009, The Nrf2-ARE cytoprotective pathway in astrocytes, Expert Rev. Mol. Med., 11, e17, 10.1017/S1462399409001094 Vilchez, 2007, Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy, Nat. Neurosci., 10, 1407, 10.1038/nn1998 Volterra, 2005, Astrocytes, from brain glue to communication elements: the revolution continues, Nat. Rev. Neurosci., 6, 626, 10.1038/nrn1722 Voutsinos-Porche, 2003, Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex, Neuron, 37, 275, 10.1016/S0896-6273(02)01170-4 Walls, 2009, Robust glycogen shunt activity in astrocytes: effects of glutamatergic and adrenergic agents, Neuroscience, 158, 284, 10.1016/j.neuroscience.2008.09.058 Wang, 2006, A mouse model for Glut-1 haploinsufficiency, Hum. Mol. Genet., 15, 1169, 10.1093/hmg/ddl032 Wilson, 1997, Antioxidant defense of the brain: a role for astrocytes, Can. J. Physiol. Pharmacol., 75, 1149, 10.1139/y97-146 Witcher, 2007, Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus, Glia, 55, 13, 10.1002/glia.20415 Zielke, 2009, Direct measurement of oxidative metabolism in the living brain by microdialysis: a review, J. Neurochem., 109, 24, 10.1111/j.1471-4159.2009.05941.x Zonta, 2003, Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation, Nat. Neurosci., 6, 43, 10.1038/nn980