Brain plasticity: cellular and metabolic aspects

我的研究计划的一个总体长期目标是了解从血液流向大脑的营养物质如何满足参与处理新信息和获得新能力的大脑区域的代谢需求。第二个目标是研究有氧糖酵解对记忆巩固过程的贡献。另一个长期目标是研究响应大脑激活的营养物质运输机制的可塑性变化。最后一个长期目标是检查禁食和体育锻炼的影响，这两者都改变了血液营养素的平衡，在与学习和记忆相关的活动增加期间对大脑代谢的影响。* 我的研究计划将为有氧糖酵解和神经元重塑之间的联系提供证据。实验将证明大脑中的有氧糖酵解及其直接终产物乳酸与学习和记忆过程之后的时间相关。还预测学习速度的变化将与有氧糖酵解增加的幅度和长度相关。第二组实验将通过评估各种糖酵解标志物与记忆任务后神经突和突触重塑标志物之间的相关性来检查有氧糖酵解对记忆巩固过程的贡献，并检查这些变化的时间过程。该项目的这一部分将为有氧糖酵解对神经元可塑性的贡献提供直接支持，特别是学习和记忆。* 葡萄糖是主要的脑代谢底物，它通过葡萄糖转运蛋白进入大脑。我们将研究这些转运蛋白在学习和记忆过程中的可塑性，并测试大脑中更活跃的区域是否会永久增加这些转运蛋白。我的研究计划的最后一部分研究了在学习和记忆过程中代谢需求增加的背景下禁食和运动对大脑代谢的影响。禁食和运动会引起葡萄糖和乳酸转运蛋白的变化。目前尚不清楚这些变化是否持久，以及它们是否对大脑可塑性机制的效率产生影响。拟议的研究计划提供了一个重要的测试神经元代谢模型。大脑中代谢可塑性发生的程度将决定我们解释使用氧合水平或葡萄糖摄取来测量大脑“激活”的实验的方式。

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.