Mechanisms of neurovascular coupling in awake animals

大脑有很高的能量需求，但实际上没有储备能量的能力。因此，它高度依赖于与局部能量需求动态匹配的恒定血液和营养流动。这一过程被称为功能性充血（FH）。FH是由活跃神经元产生的分子信号引起的，这些信号转化为局部供血血管管腔直径的增加和血流量的增加。然而，调控FH及其空间协调的细胞间信号传导过程尚不清楚。我的长期愿景是全面了解细胞间分子信号机制，这些信号机制负责翻译神经元能量需求，以协调局部和远端脑血管管腔直径和血流的变化。我们和其他人已经提供了大量证据，证明被称为星形胶质细胞的脑细胞能够“倾听”突触神经元的活动，并通过向局部血管系统发送血管扩张信号来做出反应，从而增加血流量。星形胶质细胞在FH发生和空间传导中的作用将是我们短期项目目标的首要重点。短期目标（约5年）是：

The brain has a high energy demand but virtually no reserve energy capacity. Therefore, it is highly dependent on constant blood and nutrient flow matched dynamically with local energy demand. This is accomplished by a process called functional hyperemia (FH). FH results from creation of molecular signals from active neurons that translate to increases in the lumen diameter of local blood supply vessels and increased blood flow. However, the molecular cell to cell signaling processes that regulate FH and its spatial coordination are poorly understood. My long-term vision is to gain a comprehensive understanding of the intercellular molecular signaling mechanisms responsible for translating neuronal energy need to coordinated local and distal changes in brain vascular lumen diameter and blood flow. We and others have contributed to a wealth of evidence that brain cells called astrocytes are capable of “listening” to synaptic neuronal activity and reacting by sending vasodilatory signals to the local vasculature to increase blood flow. The role of astrocytes in genesis and spatial conduction of FH will be an overarching focus of our short term program objectives. Short term objectives (~5 years) are to: