Neuron-glia metabolic coupling and plasticity.

SUMMARY The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function that has provided the basis for 2-deoxyglucose-based functional imaging with positron emission tomography (PET). Astrocytes play a central role in neurometabolic coupling, and the basic mechanism involves glutamate-stimulated aerobic glycolysis; the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. An operational model, the `astrocyte–neuron lactate shuttle', is supported experimentally by a large body of evidence, which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies. In addition, this neuron–glia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity. Thus, distinct subregions of the hippocampus are metabolically active at different time points during spatial learning tasks, suggesting that a type of metabolic plasticity, involving by definition neuron–glia coupling, occurs during learning. In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep–wake cycle, with in particular a marked induction of expression of the gene encoding for protein targeting to glycogen (PTG) following sleep deprivation. These data suggest that glial metabolic plasticity is likely to be concomitant with synaptic plasticity.

[1]  Douglas W. Barrett,et al.  Metabolic Mapping of Mouse Brain Activity after Extinction of a Conditioned Emotional Response , 2003, The Journal of Neuroscience.

[2]  P. Magistretti,et al.  Cell‐specific expression pattern of monocarboxylate transporters in astrocytes and neurons observed in different mouse brain cortical cell cultures , 2003, Journal of neuroscience research.

[3]  P. Magistretti,et al.  Selective Distribution of Lactate Dehydrogenase Isoenzymes in Neurons and Astrocytes of Human Brain , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  S. J. Martin,et al.  Reversible neural inactivation reveals hippocampal participation in several memory processes , 1999, Nature Neuroscience.

[5]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  M. Corbetta,et al.  Top-down modulation of early sensory cortex. , 1997 .

[7]  H. Haas,et al.  Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats , 1996, Neuroscience.

[8]  E. Welker,et al.  Plasticity in the barrel cortex of the adult mouse: effects of chronic stimulation upon deoxyglucose uptake in the behaving animal , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  E. Tulving,et al.  Hippocampal PET activations of memory encoding and retrieval: The HIPER model , 1998, Hippocampus.

[10]  M. Raichle,et al.  Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[11]  H. Hydén,et al.  Unraveling of important neurobiological mechanisms by the use of pure, fully differentiated neurons obtained from adult animals , 2000, Progress in Neurobiology.

[12]  C. Sherrington,et al.  On the Regulation of the Blood‐supply of the Brain , 1890, The Journal of physiology.

[13]  Changlian Zhu,et al.  The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia‐ischemia as potently as erythropoietin , 2004, Journal of neurochemistry.

[14]  R. McCarley,et al.  Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. , 1997, Science.

[15]  P. Magistretti,et al.  Pro‐inflammatory cytokines induce the transcription factors C/EBPβ and C/EBPδ in astrocytes , 2000, Glia.

[16]  Irene Tobler,et al.  Sleep deprivation modulates brain mRNAs encoding genes of glycogen metabolism , 2002, The European journal of neuroscience.

[17]  O. Porras,et al.  Glutamate Triggers Rapid Glucose Transport Stimulation in Astrocytes as Evidenced by Real-Time Confocal Microscopy , 2003, The Journal of Neuroscience.

[18]  M. Raichle,et al.  Appraising the brain's energy budget , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  H. Craig Heller,et al.  Restoration of brain energy metabolism as the function of sleep , 1995, Progress in Neurobiology.

[20]  P. Magistretti,et al.  Glucocorticoids modulate neurotransmitter‐induced glycogen metabolism in cultured cortical astrocytes , 2003, Journal of neurochemistry.

[21]  B. MacVicar,et al.  Calcium transients in astrocyte endfeet cause cerebrovascular constrictions , 2004, Nature.

[22]  M. Raichle,et al.  Searching for a baseline: Functional imaging and the resting human brain , 2001, Nature Reviews Neuroscience.

[23]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[24]  P. Magistretti,et al.  How to balance the brain energy budget while spending glucose differently , 2003, The Journal of physiology.

[25]  P. Magistretti,et al.  Noradrenaline enhances monocarboxylate transporter 2 expression in cultured mouse cortical neurons via a translational regulation , 2003, Journal of neurochemistry.

[26]  R. Shulman,et al.  Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[27]  F. Schenk,et al.  Metabolic Activation Pattern of Distinct Hippocampal Subregions during Spatial Learning and Memory Retrieval , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  P. Magistretti,et al.  Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[29]  F. Hyder,et al.  Total neuroenergetics support localized brain activity: Implications for the interpretation of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Franconi,et al.  Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity* , 2004, Journal of Biological Chemistry.

[31]  M. Raichle Functional Brain Imaging and Human Brain Function , 2003, The Journal of Neuroscience.

[32]  M. Wong-Riley,et al.  Expression and regulation of NMDA receptor subunit R1 and neuronal nitric oxide synthase in cortical neuronal cultures: Correlation with cytochrome oxidase , 1999, Journal of neurocytology.

[33]  J. Kleim,et al.  A brain adaptation view of plasticity: is synaptic plasticity an overly limited concept? , 2002, Progress in brain research.

[34]  N C Andreasen,et al.  Remembering the past: two facets of episodic memory explored with positron emission tomography. , 1995, The American journal of psychiatry.

[35]  Robert G. Shulman,et al.  Energy on Demand , 1999, Science.

[36]  B. McNaughton,et al.  Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  P. Magistretti,et al.  Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[38]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[39]  W. Webb,et al.  Neural Activity Triggers Neuronal Oxidative Metabolism Followed by Astrocytic Glycolysis , 2004, Science.

[40]  M. Buhot,et al.  Effects of medial septal or unilateral hippocampal inactivations on reference and working spatial memory in rats , 1994, Hippocampus.

[41]  G. Tononi,et al.  Modulation of Brain Gene Expression during Sleep and Wakefulness: A Review of Recent Findings , 2001, Neuropsychopharmacology.

[42]  A. Pack,et al.  Brain Glycogen Decreases with Increased Periods of Wakefulness: Implications for Homeostatic Drive to Sleep , 2002, The Journal of Neuroscience.

[43]  T. Takano,et al.  Astrocyte-mediated control of cerebral blood flow , 2006, Nature Neuroscience.

[44]  Mark F Bear,et al.  Bidirectional synaptic plasticity: from theory to reality. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[45]  B. Bontempi,et al.  Time-dependent reorganization of brain circuitry underlying long-term memory storage , 1999, Nature.

[46]  P. Magistretti,et al.  Protein targeting to glycogen mRNA expression is stimulated by noradrenaline in mouse cortical astrocytes , 2000, Glia.

[47]  M. Mintun,et al.  Nonoxidative glucose consumption during focal physiologic neural activity. , 1988, Science.

[48]  A. Baddeley,et al.  Stimulus-independent thought depends on central executive resources , 1995, Memory & cognition.

[49]  M. Karnovsky,et al.  Changes in Brain Glycogen During Slow‐Wave Sleep in the Rat , 1983, Journal of neurochemistry.

[50]  S. Thibodeau,et al.  Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. , 1996, The New England journal of medicine.

[51]  P. Magistretti,et al.  Vasoactive intestinal peptide and noradrenaline exert long-term control on glycogen levels in astrocytes: blockade by protein synthesis inhibition , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  R. Malenka The long-term potential of LTP , 2003, Nature Reviews Neuroscience.

[53]  F. Gonzalez-Lima,et al.  Quantitative histochemistry of cytochrome oxidase in rat brain , 1991, Neuroscience Letters.

[54]  P. Room,et al.  Local cerebral glucose uptake in anatomically defined structures of freely moving rats , 1989, Journal of Neuroscience Methods.

[55]  P. Magistretti,et al.  Empiricism and Rationalism: Two Paths toward the Same Goal , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[56]  B. Bontempi,et al.  Sites of Neocortical Reorganization Critical for Remote Spatial Memory , 2004, Science.

[57]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.