Neuronal–Glial Glucose Oxidation and Glutamatergic–GABAergic Function

<jats:p> Prior <jats:sup>13</jats:sup>C magnetic resonance spectroscopy (MRS) experiments, which simultaneously measured in vivo rates of total glutamate-glutamine cycling (V<jats:sub>cyc(tot)</jats:sub>) and neuronal glucose oxidation ( CMR<jats:sub>glc(ox), N</jats:sub>), revealed a linear relationship between these fluxes above isoelectricity, with a slope of ~1. In vitro glial culture studies examining glutamate uptake indicated that glutamate, which is cotransported with Na<jats:sup>+</jats:sup>, stimulated glial uptake of glucose and release of lactate. These in vivo and in vitro results were consolidated into a model: recycling of one molecule of neurotransmitter between glia and neurons was associated with oxidation of one glucose molecule in neurons; however, the glucose was taken up only by glia and all the lactate (pyruvate) generated by glial glycolysis was transferred to neurons for oxidation. The model was consistent with the 1:1 relationship between Δ CMR<jats:sub>glc(ox), N</jats:sub> and Δ V<jats:sub>cyc(tot)</jats:sub> measured by <jats:sup>13</jats:sup>C MRS. However, the model could not specify the energetics of glia and γ-amino butyric acid (GABA) neurons because quantitative values for these pathways were not available. Here, we review recent <jats:sup>13</jats:sup>C and <jats:sup>14</jats:sup>C tracer studies that enable us to include these fluxes in a more comprehensive model. The revised model shows that glia produce at least 8% of total oxidative ATP and GABAergic neurons generate ~18% of total oxidative ATP in neurons. Neurons produce at least 88% of total oxidative ATP, and take up ~26% of the total glucose oxidized. Glial lactate (pyruvate) still makes the major contribution to neuronal oxidation, but ~30% less than predicted by the prior model. The relationship observed between Δ CMR<jats:sub>glc(ox), N</jats:sub> and Δ V<jats:sub>cyc(tot)</jats:sub> is determined by glial glycolytic ATP as before. Quantitative aspects of the model, which can be tested by experimentation, are discussed. </jats:p>