Resilient versus fragile aspects of blood flow in the mammalian brain

主要研究者（最后一名、第一名、中间名）：克莱菲尔德，大卫 我们建议，以促进我们的血液分布的关键因素的理解， 个脑袋我们的重点开始与流动动力学的拓扑结构的基础angioachitecture。在 皮质是一个高度互连的表面血管网络和皮下血管网络， 显示出在分配血液和提供对闭塞的强免疫性方面是有效的。而反观 将血液从皮质表面穿梭到下面的微血管的穿透性小动脉被证明是 是大脑供血的瓶颈，也是微中风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，是否有一套不同的设计规则。 我们最初的重点是海马，因为海马神经元对缺血非常敏感。 虽然脉管系统的拓扑结构是固定的，但是个体的直径以及因此对流动的阻力可以 变化首先，脑血管的直径随着0.1Hz频率的血管运动而变化。不 已知该慢信号相位锁定到远处区域或对侧半球的血管运动， 也会被一个共同的刺激物激活我们将确定清醒的感觉刺激对 血管运动沿着途径在大区域的皮质。活性诱导相关性的发现， 血管舒缩应该是由大胆的氧合衍生的功能连接的基础 水平依赖（BOLD）功能磁共振成像（fMRI）。神经血管的第二个方面 信号传导涉及小动脉和潜在微血管毛细血管直径的变化， 调节剂由刺激诱导的神经活动释放。神经活动的机制导致了 血管收缩和血管舒张是一个谜。我们将确定血管活性物质的竞争性质 通过同时测量突触外调节剂浓度和特定神经元的激活来进行信号传导 通过血管收缩或血管舒张改变血流的影响。 我们注意到，所有拟议的实验都使用了广泛的技术，从 从行为到生理学，从探针到成像，从而也为科学发现提供了一个肥沃的试验平台 作为培养下一代神经科学家成为通才的一种手段。

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.