Resilient versus fragile aspects of blood flow in the mammalian brain

首席调查员(最后、第一、中间)：大卫·克莱菲尔德 我们建议增进我们对血液在体内分布的关键因素的理解 大脑。我们的重点是血流动力学与基础血管构筑物的拓扑结构之间的关系。在……里面 皮质，一个高度相互连接的表层血管网络和一个地下血管网络 被证明在分配血液和提供强大的闭塞免疫力方面有效。相比之下， 穿透小动脉将血液从皮质表面输送到下面的微血管。 是大脑内血液供应的瓶颈，也是微卒中后认知能力下降的场所。我们 将决定其他大脑区域是否遵循相同的血管计划，或者更确切地说，是有一套不同的设计规则。 考虑到海马神经元对缺血的高度敏感性，我们最初的重点是海马区。 虽然血管系统的拓扑结构是固定的，但个体的直径和对流动的阻力 变化。首先，在0.1赫兹的频率下，脑血管的直径随血管运动而变化。它不是 已知这一缓慢信号是否与远处或对侧大脑半球的血管运动有关 也是由普通刺激激活的。我们将确定清醒感觉刺激对 沿着大脑皮层大片区域的通路进行血管运动。活动性相关的发现 血管运动应作为大胆氧合产生的功能连通性的基础 水平相关(BOLD)功能磁共振成像(FMRI)。神经血管的第二个方面 信号涉及小动脉和潜在的微血管内管径的变化 由刺激诱导的神经活动所释放的调节剂。神经活动导致两者的机制 血管收缩和血管扩张是一个谜。我们将确定血管活性物质的竞争性 伴随突触外调节剂浓度和特异性神经元激活的信号转导 根据其对通过血管收缩或血管扩张而改变血流的影响而划分的亚型。 我们注意到，所有拟议的实验都利用了广泛的技术，包括 从行为到生理，从探针到成像，因此也为科学发现提供了一个肥沃的试验台 作为一种手段，将下一代神经科学家培养成多面手。

Principal Investigator (Last, first, middle): KLEINFELD, DAVID We propose to advance our understanding of the key factors involved in the distribution of blood within the brain. Our focus begins with the relation of flow dynamics to the topology of the underlying angioachitecture. In cortex, a highly interconnected network of surface vessels and a network of subsurface vasculature were shown to be effective in distributing blood and in providing a robust immunity to occlusions. In contrast, the penetrating arterioles that shuttle blood from the cortical surface to the underlying microvessels were shown to be a bottleneck to the supply of blood within the brain and a locus for cognitive decline after a microstroke. We will determine if other brain areas follow the same vascular plan or rather have a different set of design rules. Our initial emphasis is on hippocampus, given the great sensitivity of hippocampal neurons to ischemia. While the topology of the vasculature is fixed, the diameter and thus the resistance to flow of individual can change. First, the diameter of brain blood vessels changes with vasomotion at a frequency of 0.1 Hz. It is not known if this slow signal phase-locks to vasomotion in a distant region or in the contralateral hemisphere that is also activated by a common stimulus. We will determine the effects of awake sensory stimulation on vasomotion along pathways over large regions of cortex. The finding of activity induced correlation of vasomotion should have implications as a basis for the functional connectivity derived by bold oxygenation level dependent (BOLD) functional magnetic resonant imaging (fMRI). A second aspect of neurovascular signaling concerns changes in diameter in arterioles and potentially microvascular capillaries in response to modulators released by stimulus-induced neural activity. The mechanism by which neural activity leads to both vasoconstriction and to vasodilation is a puzzle. We will determine the competitive nature of vasoactive signaling by concomitant measure of extrasynaptic modulator concentration and activation of specific neuronal subtypes in terms of their affects on changing blood flow through vasoconstriction or vasodilation. We note that all of the proposed experiments make use of a broad range of technologies, ranging from behavior to physiology to probes to imaging, and thus provide a fertile test bed for scientific discovery as well as a means to train the next generation of neuroscientists as generalists.