The goal of this research proposal is to understand the relations between brain energy consumption and neuronal activity. Mammalian brains normally obtain their energy from oxidizing glucose. It is becoming clear that most of the energy consumption supports a particular neurotransmitter activity in which the neurotransmitter cycles through glutamine. This quantitatively relates brain energy consumption to a specific neurochemical flux. Further it shows that considering neuronal communication as the """"""""work"""""""" of the brain, the brain is an efficient organ, using nearly all its energy to do work. These results are obtained by 13C NMR of the living rat brain. Glucose, enriched with 13C is infused and this label is measured as it flows into metabolic pools of glutamate and glutamine. The rate of label flow into glutamate provides a measure of the TCA cycle flux, which evaluates brain energy consumption. The subsequent appearance of the label in glutamine allows the neurotransmitter cycling flux to be determined. The first experiments determining these fluxes were done on the human brain, which were easily done because of the non-invasive nature of the NMR method. The rat; by allowing moderate interventions, has become the subject of these intensive studies in health and disease. In addition to testing the existing model, in which both neurons and glia participate, the research will investigate the role of glycogen, a molecule whose function has not previously been well understood.
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