The Physiological Mechanisms and Role in Neural Coding of Functional Hyperemia

功能性充血的生理机制及其在神经编码中的作用

• 批准号: 9915993
• 负责人: Philip O'Herron
• 金额: $ 19.2万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9915993
• 关键词: Affect; Aging; Area; Arteries; Basic Science; Biological Models; Blood; Blood Vessels; Blood flow; Brain; Caliber; Clinical Research; Closure by clamp; Code; Consumption; Coupling; Data; Data Analyses; Defect; Disease; Dyes; Endothelial Cells; Endothelium; Felis catus; Flowers; Functional Magnetic Resonance Imaging; Future; Gardenal; Genetic; Glucose; Goals; Health; Human body; Hyperemia; Image; Imaging Techniques; Individual; Interruption; Label; Lasers; Lead; Light; Link; Location; Measures; Methods; Mus; Neurologic; Neurons; Neurophysiology - biologic function; Optics; Organ; Oxygen; Photic Stimulation; Physiological; Positioning Attribute; Proxy; Reaction; Research; Resources; Role; Signal Transduction; Source; Stimulus; Synapses; Techniques; Testing; Tissues; Travel; Vascular blood supply; Vasodilation; Visual Cortex; Water; Work; arteriole; blood perfusion; experimental study; fluorophore; hemodynamics; in vivo; millimeter; mouse model; nervous system disorder; neurological pathology; neurotransmission; neurovascular coupling; novel; novel strategies; optogenetics; prevent; relating to nervous system; response; retinotopic; sensory stimulus; temporal measurement; tool; two photon microscopy; two-photon; visual stimulus

PROJECT SUMMARY The activation of neurons in the brain leads to localized blood flow increases – a phenomenon termed functional hyperemia. Widely used hemodynamic imaging techniques, such as fMRI, take advantage of functional hyperemia to infer neural activity from vascular responses. However, the vasculature seems to overcompensate in its reaction to neuronal activity – blood flow increases over a larger region than the area of active neural tissue, and the increase in blood seems to exceed the oxygen needs of the tissue. Therefore, a deeper understanding of the degree to which blood flow changes reflect neural activity is critical for the accurate interpretation of hemodynamic imaging data. Additionally, although it is supposed that functional hyperemia is an efficient means of distributing limited resources, we know surprisingly little about how critical this blood flow increase is for the health and function of neural tissue. The overarching goal of this proposal is to understand the mechanisms and the functional role of the overshoot of blood supply in functional hyperemia. We recently found that individual vessels in the cortical parenchyma display stimulus-evoked blood flow increases even when the tissue around the vessel was unresponsive to the stimuli. In Aim 1, we will test if the increase in blood flow seen outside of the region of active neural tissue is caused by long-range propagation of arterial dilation signals through the pial network. Arterial dilation has been shown to propagate over long distances through endothelial cells in the vessel walls. We will modify a technique for disrupting this propagation using two-photon microscopy and determine if interrupting the propagation of vasodilation leads to a more precise correspondence between the locations of neural and vascular activity. In Aim 2, we will develop a technique for optically controlling the diameter of individual arterioles in vivo to study the effect of functional hyperemia on neural responses. Using two-photon optogenetics, we will prevent increased blood flow into regions of tissue which have been activated by sensory stimuli. We will analyze how the amplitude and stimulus selectivity of neuronal spiking and synaptic responses are affected by the lack of extra blood. These results will help us understand how normal neuronal function depends on robust neurovascular coupling. This in turn will shed light on whether the neurovascular coupling defects seen in many diseases are the cause of the accompanying neurological disorders. This proposal will help establish techniques and model systems for future studies aimed at understanding how neural activity leads to, and in turn depends on, local blood flow changes.

项目摘要 大脑中神经元的激活导致局部血流量增加-这种现象被称为 功能性充血广泛使用的血流动力学成像技术，如fMRI，利用 功能性充血以从血管反应推断神经活动。然而，血管系统似乎 在其对神经元活动的反应中过度补偿-血流量在比大脑皮层面积更大的区域上增加。 活跃的神经组织，血液的增加似乎超过了组织的氧气需求。因此 更深入地了解血流变化反映神经活动的程度对于研究神经系统的功能至关重要。 血流动力学成像数据的准确解释。此外，虽然它被认为是功能性的， 充血是分配有限资源的有效手段，但我们对充血的重要性知之甚少。 这种血流量的增加是为了神经组织的健康和功能。本提案的总体目标是 是为了了解机制和功能作用的血液供应超调， 充血。我们最近发现皮层实质中的单个血管显示刺激诱发的 即使当血管周围的组织对刺激无反应时，血流也会增加。在目标1中，我们 测试在活跃神经组织区域外看到的血流增加是否是由长距离 动脉扩张信号通过软脑膜网络的传播。动脉扩张已经被证明可以传播 通过血管壁中的内皮细胞长距离传播。我们将改进一种技术来破坏它 使用双光子显微镜检查传播，并确定中断血管舒张的传播是否会导致 神经和血管活动的位置之间的更精确的对应关系。在目标2中，我们将开发 一种用于在体内光学控制单个小动脉直径以研究功能性微动脉的影响的技术， 充血对神经反应的影响使用双光子光遗传学，我们将阻止增加的血液流入 被感官刺激激活的组织区域。我们将分析振幅和 神经元尖峰和突触反应的刺激选择性受到缺乏额外血液的影响。这些 这些结果将帮助我们理解正常的神经元功能是如何依赖于强大的神经血管耦合的。这 反过来将揭示在许多疾病中看到的神经血管耦合缺陷是否是导致 伴随的神经系统疾病这一建议将有助于建立技术和模型系统， 未来的研究旨在了解神经活动如何导致并反过来取决于局部血流 变化