The human brain accounts for 2% of total body weight, though it consumes 20% of the body's energy supply. Most of this energy is provided by the complete oxidation of glucose to carbon dioxide and water, though some fraction of glucose undergoes aerobic glycolysis without concomitant oxidative phosphorylation. Elevation in neuronal activity increases aerobic glycolysis due to the disproportionate increase in blood flow and glucose utilization greater than oxygen consumption. Since aerobic glycolysis produces significantly less energy than complete oxidation of glucose, its role in cellular activities has been overlooked, though its presence in the resting brain has been known for several decades. In this thesis, we investigate three aspects of resting aerobic glycolysis using positron emission tomography. First, we characterize the regional distribution of aerobic glycolysis in the awake, eyes closed human brain. We show that brain regions with high levels of functional activity in the resting state, including the default network and prefrontal cortex, have elevated aerobic glycolysis. In addition, we show that aerobic glycolysis is modulated by prior task performance. Performance of a complex visuomotor rotation learning task increases aerobic glycolysis in premotor cortex for several hours following task completion. Further, we show that regional brain metabolism is correlated to neurotransmitter receptor density. Aerobic glycolysis is highest in regions with a balanced density of excitatory and inhibitory receptors. Taken together, these results demonstrate the functional significance of resting aerobic glycolysis and its modulation by transient functional activity. These data provide supporting evidence for the synaptic homeostasis hypothesis, indicating elevation in brain metabolism, specifically aerobic glycolysis, during wakefulness associated with alterations in synaptic strength and receptor density.
|Advisor:||Raichle, Marcus E.|
|Commitee:||Mintun, Mark A., Perlmutter, Joel, Snyder, Larry, Thach, W. Thomas, Van Essen, David|
|School:||Washington University in St. Louis|
|Department:||Biology & Biomedical Sciences (Neurosciences)|
|School Location:||United States -- Missouri|
|Source:||DAI-B 71/04, Dissertation Abstracts International|
|Keywords:||Aerobic glycolysis, Brain, Energy metabolism, Learning, Positron emission tomography|
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