Resilient versus fragile aspects of blood flow in the mammalian brain

首席研究员（最后、第一位、中间）：KLEINFELD、DAVID 我们建议加深对血液在体内分布的关键因素的理解 大脑。我们的重点始于流动动力学与基础血管结构拓扑的关系。在 皮层是一个高度互连的表面血管网络和地下脉管系统网络 经证明可有效分配血液并提供强大的闭塞免疫力。相比之下， 穿透性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，也是微中风后认知能力下降的场所。我们 将确定其他大脑区域是否遵循相同的血管计划，或者更确切地说有一套不同的设计规则。 鉴于海马神经元对缺血非常敏感，我们最初的重点是海马。 虽然脉管系统的拓扑结构是固定的，但个体的直径和流动阻力可以 改变。首先，脑血管直径随着频率为 0.1 Hz 的血管舒缩而变化。它不是 已知这种慢信号是否与远处区域或对侧半球的血管运动锁相 也被共同的刺激激活。我们将确定清醒感官刺激对 沿着皮层大片区域的路径进行血管舒缩。活动诱导相关性的发现 血管舒缩应该作为大胆氧合产生的功能连接的基础具有影响 水平相关（BOLD）功能磁共振成像（fMRI）。神经血管的第二个方面 信号传导涉及小动脉和潜在微血管毛细血管直径的变化，以响应 由刺激诱导的神经活动释放的调节剂。神经活动导致这两种情况的机制 血管收缩和血管舒张是一个谜。我们将确定血管活性的竞争性质 通过同时测量突触外调节剂浓度和特定神经元的激活来发出信号 亚型通过血管收缩或血管舒张对血流变化的影响。 我们注意到所有提出的实验都利用了广泛的技术，从 从行为到生理学到探索到成像，从而为科学发现提供了肥沃的试验台 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.