Excitatory and Inhibitory Activity Contributions to Hemodynamic Signals

兴奋性和抑制性活动对血流动力学信号的贡献

• 批准号: 9506875
• 负责人: ALBERTO L VAZQUEZ
• 金额: $ 33.64万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9506875
• 关键词: Animals; Automobile Driving; Basic Science; Blood; Blood Vessels; Blood Volume; Blood flow; Brain; Calcium; Cells; Cerebrovascular Circulation; Clinical Research; Cognitive; Data; Development; Disease; Electrophysiology (science); Ensure; Excitatory Amino Acid Antagonists; Forelimb; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Glutamates; Goals; Health; Human; Image; Impairment; Knowledge; Laboratories; Laser-Doppler Flowmetry; Maps; Measurement; Measures; Methodology; Methods; Modeling; Neurons; Pharmaceutical Preparations; Pharmacology; Population; Positioning Attribute; Process; Property; Regulation; Role; Sensory; Signal Transduction; Synapses; Synaptic Transmission; Testing; Work; blood oxygen level dependent; brain behavior; cerebral blood volume; design; excitatory neuron; experimental study; gamma-Aminobutyric Acid; hemodynamics; imaging study; in vivo; inhibitory neuron; innovation; interest; mouse model; neurovascular; novel; optical imaging; optogenetics; relating to nervous system; response; somatosensory; tool; two-photon

PROJECT SUMMARY/ABSTRACT Most approaches to assess brain function and connectivity, including functional magnetic resonance imaging (fMRI) and optical imaging of intrinsic signals (OIS), rely on activity-evoked changes in cerebral blood flow, blood volume and/or blood oxygenation as indirect measures of neural activity. While these hemodynamic methods are immensely valuable to map brain function and connectivity in humans and animals, fundamental gaps remain in our understanding of neuro-vascular mechanisms due to its complexity and methodological difficulties. This gap in knowledge greatly impedes our understanding of the driving neuronal processes behind BOLD fMRI findings of brain function, dysfunction and development. The goal of this proposal is to determine the role of excitatory and inhibitory neuronal activity, including glutamatergic and GABAergic synaptic activity, in vascular regulation and their representation in hemodynamic signals. To activate specific neuronal sub-populations in vivo, novel optogenetic mouse models expressing Channelrhodopsin-2 (ChR2) in cortical excitatory or inhibitory neurons will be used. These optogenetic models will be combined with an innovative approach to concurrently record neural and vascular signals under pharmacological conditions designed to modulate glutamatergic and GABAergic synaptic transmission. Neural activity will be measured by electrophysiology and two-photon calcium imaging. Vascular signals of blood flow will be obtained by laser Doppler flowmetry, while OIS will be used to image changes in cerebral blood volume and blood oxygenation (directly analogous to fMRI). These data will then be used to model and integrate excitatory and inhibitory activity contributions to hemodynamic signals. This work will have a tremendous impact by advancing our understanding of relevant neuro-vascular mechanisms as well as establish a more concrete framework that can allow for a deeper understanding of the neuronal processes behind hemodynamic alterations in brain development and dysfunction.

项目摘要/摘要 评估大脑功能和连通性的大多数方法，包括功能磁共振成像 （fMRI）和内在信号（OIS）的光学成像依赖于活动引起的脑血流的变化， 血液体积和/或血液氧合作为神经活动的间接度量。而这些血流动力学 方法对于映射人类和动物的脑功能和连通性非常有价值，基本 由于其复杂性和方法论，我们对神经血管机制的理解仍然存在于我们的理解 困难。知识的差距极大地阻碍了我们对驱动神经元过程的理解 大脑功能，功能障碍和发育的大胆FMRI发现背后。该提议的目的是 确定兴奋性和抑制性神经元活性的作用，包括谷氨酸能和GABA能 突触活动，血管调节及其在血液动力学信号中的表示。激活特定 在体内的神经元亚群，新型的光遗传小鼠模型，表达通道Ropopsin-2（ChR2） 将使用皮质兴奋性或抑制性神经元。这些光遗传模型将与 在药理条件下同时记录神经和血管信号的创新方法 设计用于调节谷氨酸能和GABA能突触传播。神经活动将通过 电生理学和两光子钙成像。血流的血管信号将通过激光获得 多普勒流量指定，而OIS将用于图像大脑血容和血液氧合的变化 （直接类似于fMRI）。然后，这些数据将用于建模和整合兴奋性和抑制性 对血液动力学信号的活性贡献。这项工作将通过推进我们的 了解相关的神经血管机制，并建立一个更具体的框架 可以更深入地了解大脑血液动力学改变背后的神经元过程 开发和功能障碍。