Grant: Discovery Grants Program - Individual

An overarching long-term objective of my research program is to understand how nutrients that flow from the blood to the brain provide for the metabolic needs of brain regions involved in the processing of new information and the acquisition of new abilities. A secondary goal is to examine the contribution of aerobic glycolysis to the memory consolidation processes. Another long-term goal is to examine the plastic changes in the transport mechanisms of nutrients in response to brain activation. A final long-term goal is to examine the impact of fasting and physical exercise, which both change the balance of blood-borne nutrients, on brain metabolism during the increased activity associated with learning and memory. My program of research will provide evidence for the link between aerobic glycolysis and neuronal remodeling. The experiments will demonstrate that aerobic glycolysis in the brain and its immediate end-product, lactate, is temporally associated with the period that follows learning and memory processing. It is also predicted that variation in learning speed will correlate with the amplitude and length of the increase in aerobic glycolysis. A second set of experiments will examine the contribution of aerobic glycolysis to the memory consolidation processes by evaluating the correlation between various glycolysis markers and markers of neurite and synaptic remodeling following a memory task and examine the time course of these changes. This part of the project will provide direct support for the contribution of aerobic glycolysis to neuronal plasticity in general and learning and memory in particular. Glucose is the main brain metabolic substrate and it enters the brain through glucose transporters. We will examine the plasticity of these transporters during learning and memory and test if brain areas that are more often active see a permanent increase in these transporters. The final part of my research program examines the impact of fasting and exercise on brain metabolism in the context of the increase in metabolic requirement during learning and memory. Fasting and exercise produce changes in glucose and lactate transporters. It is unknown if these changes are long-lasting and if they have an impact on the efficiency of the mechanism underlying brain plasticity. The proposed research program provides a crucial test of neuronal metabolic models. The extent to which metabolic plasticity occurs in the brain will determine the way we interpret experiments that measure brain "activation" using oxygenation levels or glucose uptake.