Metabolic Coupling and the Energy Substrate of Computation

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Metabolic Coupling and the Energy Substrate of Computation

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  • 1Citationpaper:paper-b5187822d92aThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 7Citationpaper:paper-ba34820dbdb5The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 8Citationpaper:paper-cfb9b6251910The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 1Citationpaper:paper-b5187822d92aThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 9Citationpaper:paper-46b96b226367The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference The largest continuously running energy charge in the brain is the Na^+/K^+-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na^+ ions and one H^+ against counter-transport of one K^+, producing a Na^+ load whose extrusion is immediatel...

  • 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference0 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference1. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference2 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference3. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference4 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference5. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference6 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference7. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference8 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 2Citationpaper:paper-9278da39d4e6The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference9. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference0 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference1. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference2 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference3. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference4 The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-K_m isoform—is enriched on neurons 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference5. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference6 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference7 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference8 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 3Citationpaper:paper-75ba3338cfe7The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference9 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference0 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference1 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference2 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference3 The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}fig:sec6-lactate-rescue). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference4 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference5, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference6 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference7, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference8 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 4Citationpaper:paper-32f78d7dd214The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference9, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference0 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference1, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference2 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference3, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference4 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference5, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference6 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference7, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference8 If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes 5Citationpaper:paper-8f9cb784fc32The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference9, and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference0 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference1 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference2 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference3 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference4 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference5 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference6 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference7 The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference8 Human positron-emission-tomography measurements of aerobic glycolysis (AG)—the regional excess of glucose consumption over oxygen consumption / 6—add a layer that rodent slice work does not capture (Figure {ref}fig:sec6-aerobic-glycolysis). In 33 neurologically normal young adults, resting AG is non-uniform across cortex, elevated in medial and lateral prefrontal, posterior cingulate / precuneus, and lateral parie...

  • 6Citationpaper:paper-6db6df1f36aaThe largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference9 Human positron-emission-tomography measurements of aerobic glycolysis (AG)—the regional excess of glucose consumption over oxygen consumption / 6—add a layer that rodent slice work does not capture (Figure {ref}fig:sec6-aerobic-glycolysis). In 33 neurologically normal young adults, resting AG is non-uniform across cortex, elevated in medial and lateral prefrontal, posterior cingulate / precuneus, and lateral parie...

  • 7Citationpaper:paper-ba34820dbdb5The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference0 Human positron-emission-tomography measurements of aerobic glycolysis (AG)—the regional excess of glucose consumption over oxygen consumption / 6—add a layer that rodent slice work does not capture (Figure {ref}fig:sec6-aerobic-glycolysis). In 33 neurologically normal young adults, resting AG is non-uniform across cortex, elevated in medial and lateral prefrontal, posterior cingulate / precuneus, and lateral parie...

  • 7Citationpaper:paper-ba34820dbdb5The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference1 Together these findings do not establish that ANLS is the universal energetic mode of brain computation. They establish a more restricted and testable picture: AG—an anatomical proxy for glycolytic over oxidative flux—is regionally and developmentally non-uniform in humans, it peaks where and when synaptic turnover is highest, and in rodents the requirement for astrocytic lactate scales with the computational demand...

  • 7Citationpaper:paper-ba34820dbdb5The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference2 Computational models of astrocyte–neuron interaction (§{ref}sec:computational-models) frequently treat metabolic coupling as a steady supply term or as an on/off switch tied to activity. The empirical literature rejects both simplifications. Neuronal glucose uptake is fast and activity-regulated; astrocytic lactate export is slower and engaged selectively under load [diazgarcia_2017_cellmetabolism,dembitskaya_2022...

  • 7Citationpaper:paper-ba34820dbdb5The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference3 Computational models of astrocyte–neuron interaction (§{ref}sec:computational-models) frequently treat metabolic coupling as a steady supply term or as an on/off switch tied to activity. The empirical literature rejects both simplifications. Neuronal glucose uptake is fast and activity-regulated; astrocytic lactate export is slower and engaged selectively under load [diazgarcia_2017_cellmetabolism,dembitskaya_2022...

  • 7Citationpaper:paper-ba34820dbdb5The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference4 Computational models of astrocyte–neuron interaction (§{ref}sec:computational-models) frequently treat metabolic coupling as a steady supply term or as an on/off switch tied to activity. The empirical literature rejects both simplifications. Neuronal glucose uptake is fast and activity-regulated; astrocytic lactate export is slower and engaged selectively under load [diazgarcia_2017_cellmetabolism,dembitskaya_2022...

  • 7Citationpaper:paper-ba34820dbdb5The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}sec:synaptic-modulation. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...content/06_metabolic_coupling.md:line 8Open reference5 Computational models of astrocyte–neuron interaction (§{ref}sec:computational-models) frequently treat metabolic coupling as a steady supply term or as an on/off switch tied to activity. The empirical literature rejects both simplifications. Neuronal glucose uptake is fast and activity-regulated; astrocytic lactate export is slower and engaged selectively under load [diazgarcia_2017_cellmetabolism,dembitskaya_2022...

  • ... 6 additional anchors in refs_json

References

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  2. [stobart_2013_frontcell] paper:paper-9278da39d4e6 “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  3. [pellerin_1994_procnatl] paper:paper-75ba3338cfe7 “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  4. [pellerin_2007_glia] paper:paper-32f78d7dd214 “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  5. [pellerin_2012_jcereb] paper:paper-8f9cb784fc32 “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  6. [falkowska_2015_ijms] paper:paper-6db6df1f36aa “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  7. [beard_2022_frontphysiol] paper:paper-ba34820dbdb5 “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  8. [yellen_2018_cellbiology] paper:paper-cfb9b6251910 “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  9. [allaman_2015_frontneurosci] paper:paper-46b96b226367 “The largest continuously running energy charge in the brain is the Na$^+$/K$^+$-ATPase, and a substantial fraction of it runs in astrocytes to support the two clearances described in §{ref}`sec:synaptic-modulation`. Glutamate uptake by GLT-1 is thermodynamically coupled to the co-transport of three Na$^+$ ions and one H$^+$ against counter-transport of one K$^+$, producing a Na$^+$ load whose extrusion is immediatel...”
  10. [halestrap_1999_biochemical] paper:paper-8065ec86aa64 “The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-$K_m$ isoform—is enriched on neurons [halestrap_1999_biochemical,halestrap_2013_molecularaspects,pierre_2005_neurochemistry]. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...”
  11. [halestrap_2013_molecularaspects] paper:paper-d684cbb7b17e “The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-$K_m$ isoform—is enriched on neurons [halestrap_1999_biochemical,halestrap_2013_molecularaspects,pierre_2005_neurochemistry]. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...”
  12. [pierre_2005_neurochemistry] paper:paper-d6f4762cb136 “The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-$K_m$ isoform—is enriched on neurons [halestrap_1999_biochemical,halestrap_2013_molecularaspects,pierre_2005_neurochemistry]. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...”
  13. [dimmer_2000_biochemical] paper:paper-464081b7a79a “The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-$K_m$ isoform—is enriched on neurons [halestrap_1999_biochemical,halestrap_2013_molecularaspects,pierre_2005_neurochemistry]. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...”
  14. [kirk_2000_embo] paper:paper-7b721c5f080b “The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-$K_m$ isoform—is enriched on neurons [halestrap_1999_biochemical,halestrap_2013_molecularaspects,pierre_2005_neurochemistry]. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...”
  15. [alberini_2018_glia] paper:paper-819b53235252 “The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-$K_m$ isoform—is enriched on neurons [halestrap_1999_biochemical,halestrap_2013_molecularaspects,pierre_2005_neurochemistry]. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...”
  16. [gibbs_2016_frontintegr] paper:paper-30c9f87c67ac “The monocarboxylate transporter (MCT) family encodes the molecular conduit. MCT1 and MCT4 are expressed on astrocytes and on the vascular side, and MCT2—a high-affinity, low-$K_m$ isoform—is enriched on neurons [halestrap_1999_biochemical,halestrap_2013_molecularaspects,pierre_2005_neurochemistry]. MCT4 is kinetically adapted to export high concentrations of lactate from glycolytic cells and is the predicted dominan...”
  17. [suzuki_2011_cell] paper:paper-1829615f8d75 “The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}`fig:sec6-lactate-rescue`). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...”
  18. [newman_2011_plosone] paper:paper-16e6ed98049d “The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}`fig:sec6-lactate-rescue`). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...”
  19. [vezzoli_2020_cerebral] paper:paper-b7318ec88980 “The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}`fig:sec6-lactate-rescue`). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...”
  20. [bouryjamot_2016_molpsychiatry] paper:paper-baef06af1040 “The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}`fig:sec6-lactate-rescue`). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...”
  21. [tadi_2015_plosone] paper:paper-22c77e3f9b83 “The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}`fig:sec6-lactate-rescue`). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...”
  22. [descalzi_2019_communbiol] paper:paper-40aaf6eec5f7 “The strongest behavioural evidence for a functional ANLS comes from a family of pharmacological and antisense experiments in which inhibition of astrocytic glycogenolysis or of MCT-mediated lactate flux impairs learning or plasticity, and exogenous L-lactate—but not equicaloric glucose—rescues the deficit (Figure {ref}`fig:sec6-lactate-rescue`). In rat hippocampus, intrahippocampal 1,4-dideoxy-1,4-imino-d-arabinitol...”
  23. [machler_2016_cellmetabolism] paper:paper-aad5d2879183 “If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes [pellerin_1994_procnatl], and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...”
  24. [sanmartin_2013_plosone] paper:paper-194e2c412ea5 “If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes [pellerin_1994_procnatl], and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...”
  25. [hall_2012_neuroscience] paper:paper-a00cdcfc37b1 “If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes [pellerin_1994_procnatl], and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...”
  26. [lundgaard_2015_natcommun] paper:paper-c0ab0710be9a “If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes [pellerin_1994_procnatl], and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...”
  27. [diazgarcia_2017_cellmetabolism] paper:paper-42100a283aa1 “If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes [pellerin_1994_procnatl], and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...”
  28. [jha_2018_experimentalneurolog] paper:paper-3823a64302c2 “If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes [pellerin_1994_procnatl], and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...”
  29. [jha_2020_frontcell] paper:paper-2db5001fff52 “If astrocytes are the primary glycolytic cell during activity, activity-evoked 2-deoxyglucose or glucose uptake should localise preferentially to astrocytes. The direct measurements do not agree. Glutamate uptake stimulates aerobic glycolysis in cultured astrocytes [pellerin_1994_procnatl], and in vivo two-photon imaging with the Laconic FRET lactate sensor reveals a steady-state lactate gradient from astrocytes to...”
  30. [yang_2014_procnatl] paper:paper-bfdd56cbdaf9 “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  31. [brooks_2020_redoxbiology] paper:paper-24cee1e8837c “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  32. [dienel_2012_jcereb] paper:paper-664d463114bc “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  33. [dienel_2012_asnneuro] paper:paper-b8988109da93 “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  34. [dienel_2013_neurochemistry] paper:paper-76190760a4ad “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  35. [steinman_2016_frontintegr] paper:paper-49a93776098f “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  36. [lee_2012_nature] paper:paper-22801498 “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  37. [philips_2021_cellreports] paper:6ab4d25a-c4ef-4a7e-95c3-24b2fce544a8 “The best-attested resolution—provisional, but internally consistent—is that neurons can use glucose directly on fast time-scales, and that astrocyte-derived lactate becomes rate-limiting only for slower, load-dependent processes (long-term memory consolidation, high-frequency LTP, learning-induced structural plasticity). Time-scale separation also helps reconcile the imaging disagreement: two-photon 2DG-IR and Lacon...”
  38. [vaishnavi_2010_procnatl] paper:paper-36666c0f41b9 “Human positron-emission-tomography measurements of aerobic glycolysis (AG)—the regional excess of glucose consumption over oxygen consumption / 6—add a layer that rodent slice work does not capture (Figure {ref}`fig:sec6-aerobic-glycolysis`). In 33 neurologically normal young adults, resting AG is non-uniform across cortex, elevated in medial and lateral prefrontal, posterior cingulate / precuneus, and lateral parie...”
  39. [goyal_2014_cellmetabolism] paper:paper-cdd6bd06868f “Human positron-emission-tomography measurements of aerobic glycolysis (AG)—the regional excess of glucose consumption over oxygen consumption / 6—add a layer that rodent slice work does not capture (Figure {ref}`fig:sec6-aerobic-glycolysis`). In 33 neurologically normal young adults, resting AG is non-uniform across cortex, elevated in medial and lateral prefrontal, posterior cingulate / precuneus, and lateral parie...”
  40. [dembitskaya_2022_procnatl] paper:paper-cd0fabafa821 “Human positron-emission-tomography measurements of aerobic glycolysis (AG)—the regional excess of glucose consumption over oxygen consumption / 6—add a layer that rodent slice work does not capture (Figure {ref}`fig:sec6-aerobic-glycolysis`). In 33 neurologically normal young adults, resting AG is non-uniform across cortex, elevated in medial and lateral prefrontal, posterior cingulate / precuneus, and lateral parie...”
  41. [cunnane_2020_natrev] paper:paper-https://openalex.org/W3044114834 “Together these findings do not establish that ANLS is the universal energetic mode of brain computation. They establish a more restricted and testable picture: AG—an anatomical proxy for glycolytic over oxidative flux—is regionally and developmentally non-uniform in humans, it peaks where and when synaptic turnover is highest, and in rodents the requirement for astrocytic lactate scales with the computational demand...”

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