This study investigates the relationship between brain glucose metabolism and glutamatergic neuronal activity in the rat cortex using in vivo 13C NMR spectroscopy. The researchers measured the rates of the tricarboxylic acid (TCA) cycle and glutamine (Gln) synthesis, which allowed them to calculate the rates of oxidative glucose metabolism and glutamate-neurotransmitter cycling between neurons and astrocytes. The results showed a close 1:1 stoichiometric relationship between oxidative glucose metabolism and glutamate-neurotransmitter cycling, indicating that most cortical energy production supports functional glutamatergic neuronal activity. This finding suggests that brain activation studies, which map cortical oxidative glucose metabolism, provide a quantitative measure of synaptic glutamate release. The study used three groups of rats under different anesthetic conditions to measure cerebral metabolism. The results showed that under isoelectric conditions, the rate of glutamate-neurotransmitter cycling was almost completely abolished. The rate of cerebral oxidative glucose consumption was found to be closely correlated with the rate of glutamate-neurotransmitter cycling, with a strong positive correlation (r = 0.94) and a slope of 1.04, indicating a 1:1 stoichiometric relationship. The study also considered the potential contribution of GABA to neurotransmitter cycling and found that including a maximum contribution of GABA cycling increased the slope and molar stoichiometric ratio by less than 30%. The results support a model of coupling between astrocytic glucose consumption and glutamatergic neuronal activity, where the energy required for glutamate uptake and conversion to Gln is balanced by glycolytic ATP production. In conclusion, the study demonstrates a stoichiometric relationship between glutamate-neurotransmitter cycling and oxidative glucose metabolism in the rat cerebral cortex. Under mild anesthesia, glutamate-neurotransmitter cycling accounts for more than 80% of total glucose oxidation, suggesting that synaptic glutamate release may be a control step for cortical glucose consumption. The findings highlight the quantitative coupling between cerebral glucose metabolism and specific neurophysiological processes of functional activity, namely glutamate-neurotransmitter release.This study investigates the relationship between brain glucose metabolism and glutamatergic neuronal activity in the rat cortex using in vivo 13C NMR spectroscopy. The researchers measured the rates of the tricarboxylic acid (TCA) cycle and glutamine (Gln) synthesis, which allowed them to calculate the rates of oxidative glucose metabolism and glutamate-neurotransmitter cycling between neurons and astrocytes. The results showed a close 1:1 stoichiometric relationship between oxidative glucose metabolism and glutamate-neurotransmitter cycling, indicating that most cortical energy production supports functional glutamatergic neuronal activity. This finding suggests that brain activation studies, which map cortical oxidative glucose metabolism, provide a quantitative measure of synaptic glutamate release. The study used three groups of rats under different anesthetic conditions to measure cerebral metabolism. The results showed that under isoelectric conditions, the rate of glutamate-neurotransmitter cycling was almost completely abolished. The rate of cerebral oxidative glucose consumption was found to be closely correlated with the rate of glutamate-neurotransmitter cycling, with a strong positive correlation (r = 0.94) and a slope of 1.04, indicating a 1:1 stoichiometric relationship. The study also considered the potential contribution of GABA to neurotransmitter cycling and found that including a maximum contribution of GABA cycling increased the slope and molar stoichiometric ratio by less than 30%. The results support a model of coupling between astrocytic glucose consumption and glutamatergic neuronal activity, where the energy required for glutamate uptake and conversion to Gln is balanced by glycolytic ATP production. In conclusion, the study demonstrates a stoichiometric relationship between glutamate-neurotransmitter cycling and oxidative glucose metabolism in the rat cerebral cortex. Under mild anesthesia, glutamate-neurotransmitter cycling accounts for more than 80% of total glucose oxidation, suggesting that synaptic glutamate release may be a control step for cortical glucose consumption. The findings highlight the quantitative coupling between cerebral glucose metabolism and specific neurophysiological processes of functional activity, namely glutamate-neurotransmitter release.