Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity.

Sibson, Nicola R.; Dhankhar, Ajay; Mason, Graeme F.; Rothman, Douglas L.; Behar, Kevin L.; Shulman, Robert G.

doi:10.1073/pnas.95.1.316

Cited by 897Neuroscience and Neuropharmacology ResearchAdvanced MRI Techniques and ApplicationsAmino Acid Enzymes and Metabolism

Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity.

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Sibson, Nicola R., Dhankhar, Ajay, Mason, Graeme F., Rothman, Douglas L., Behar, Kevin L., Shulman, Robert G.·1998·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.95.1.316PMC PMC18211

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Abstract

To determine the relationship between cerebral Glc metabolism and glutamatergic neuronal function, we used 13C NMR spectroscopy to measure, simultaneously, the rates of the tricarboxylic acid cycle and Gln synthesis in the rat cortex in vivo. From these measurements, we calculated the rates of oxidative Glc metabolism and glutamate-neurotransmitter cycling between neurons and astrocytes (a quantitative measure of glutamatergic neuronal activity). By measuring the rates of the tricarboxylic acid cycle and Gln synthesis over a range of synaptic activity, we have determined the stoichiometry between oxidative Glc metabolism and glutamate-neurotransmitter cycling in the cortex to be close to 1:1. This finding indicates that the majority of cortical energy production supports functional (synaptic) glutamatergic neuronal activity. Another implication of this result is that brain activation studies, which map cortical oxidative Glc metabolism, provide a quantitative measure of synaptic glutamate release.

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The same stoichiometric coupling applies to rat and human cerebral cortex in vivo.
“Remarkably, these studies have shown that the same stoichiometric coupling applies to rat [32] and human [33] cerebral cortex in vivo.”
From Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution (2011) · cites this paper as [32]
Total glucose use by neurons and astrocytes together is coupled directly to glutamate-mediated synaptic transmission, which accounts for 80-90% of total glucose use in the cerebral cortex.
“As a consequence, the total glucose use by neurons and astrocytes together is coupled directly to glutamate-mediated synaptic transmission [32], [34], [36], which accounts for 80–90% of total glucose use in the cerebral cortex [32].”
From Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution (2011) · cites this paper as [32]

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Authors: Sibson, N. R., Dhankhar, A., Mason, G. F., Rothman, D. L., Behar, K. L., & Shulman, R. G.
Affiliations: Yale University (US)
ORCID: Sibson, Nicola R.
Mason, Graeme F.
Rothman, Douglas L.
Behar, Kevin L.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1998-01-06
Volume: 95
Issue: 1
Pages: 316-321
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.95.1.316
PMC: PMC18211
OpenAlex: W2053268711
Cited by: 897
References: 34
Citations by year: 2026: 19 · 2025: 26 · 2024: 18 · 2023: 21 · 2022: 32 · 2021: 48 · 2020: 23 · 2019: 27 · 2018: 33 · 2017: 37 · 2016: 30 · 2015: 20 · 2014: 45 · 2013: 34 · 2012: 39
FWCI: 13.71
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (2RO1 DK27121, R01DK027121)
National Institute of Neurological Disorders and Stroke (R01 NS 34813, R29NS032126, R29 NS32126, R01NS034813)
National Center for Research Resources
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD032573)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords: brain glucose metabolism, TCA cycle, glutamine synthesis, glucose oxidation, astrocytes, synaptic activity, glutamate release, 13C NMR
MeSH terms: Anesthetics, Animals, Blood Glucose, Cerebral Cortex, Citric Acid Cycle, Electroencephalography, gamma-Aminobutyric Acid, Glucose, Glutamine, Kinetics, Male, Neurons, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Rats, Sprague-Dawley, Neurotransmitter Agents, Rats

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Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity.

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