Functional relationship between neural, metabolic and hemodynamic responses

神经、代谢和血流动力学反应之间的功能关系

• 批准号: 7989208
• 负责人: ALBERTO L VAZQUEZ
• 金额: $ 12.36万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989208
• 关键词: Animal Model; Animals; Basic Science; Blood; Blood Vessels; Blood Volume; Blood capillaries; Blood flow; Brain; Brain imaging; Calcium; Caliber; Cerebrovascular Circulation; Cerebrum; Clinical; Clinical Research; Cognitive; Complex; Core-Binding Factor; Detection; Development; Electrodes; Erythrocytes; Event; Evolution; Fluorescent Dyes; Functional Magnetic Resonance Imaging; Goals; Hemoglobin; Human; Image; Knowledge; Lasers; Light; Location; Maps; Measures; Mentorship; Metabolic; Metabolism; Metals; Methods; Microscopy; NADH; Neuraxis; Neurons; Neurosciences; Optical Methods; Oxygen; Oxygen Consumption; Physiological; Physiology; Plasma; Population; Property; Proteins; Research; Research Personnel; Resolution; Signal Transduction; Site; Specificity; Stimulus; Structure; Surface; Tissues; Tracer; Training; Vascular System; Visual Cortex; Work; absorption; analog; base; blood oxygen level dependent; brain research; calcium indicator; capillary; career; fluorescence imaging; hemodynamics; imaging modality; in vivo; millimeter; mouse model; optical imaging; orientation columns; programs; public health relevance; relating to nervous system; research study; response; stem; success; tool; two-photon

DESCRIPTION (provided by applicant): The objective of the proposed work is to determine and characterize the spatio-temporal limits of the metabolic and hemodynamic responses that result from evoked neural activity. For this purpose a genetically enhanced mouse model expressing the light-sensitive protein Channelrhodopsin-2 will be used whereby the neuronal activity can be controlled through the modulation of the diameter and intensity of a light stimulus delivered directly onto the surface of the brain (photo-stimulus). First, the minimum neuronal activity that elicits a blood flow response will be determined using two-photon microscopy with sub-micrometer resolution. The size and strength of the neuronal activity will be characterized using a calcium indicator. Then, an intra-vascular fluorescent dye will be used to measure corresponding changes in blood velocity and vessel diameter in capillaries. Second, the consistency of these findings and the effect of resolution will be investigated by measuring the functional cerebral blood flow, metabolic and overall hemodynamic responses using larger- scale optical imaging with resolution of tens of micrometers. Specifically, the following optical methods will be used to measure blood flow, metabolic and overall hemodynamic responses to neural activity: laser speckle imaging, intrinsic auto-fluorescence imaging and optical imaging of intrinsic signal, respectively. The latter is a direct analog of blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI). As a result of this project, the spatio-temporal limits of the metabolic and hemodynamic responses will be uncovered with unparalleled resolution. In addition, sufficient knowledge will be obtained to elucidate the theoretical and practical requirements of current brain research tools like fMRI to detect activities encoded in the hemodynamic response that may be thought to be undetectable. This work will have a tremendous impact in brain imaging studies of function in animals and humans, including clinical and basic science research. To perform the proposed studies I will undergo training in two-photon imaging of brain function and complementary optical imaging methods, and in electrophysiological recording of neuronal activity. A unique combination of local and national experts will provide and oversee the necessary training. This proposal is vital in fulfilling my ultimate career goal of attaining an independent and successful research program that focuses on imaging normal and pathological brain function. PUBLIC HEALTH RELEVANCE: The hemodynamic response induced by neural activity is, and has been, the principal means of studying brain function in animals and humans. Methods like functional magnetic resonance imaging are now essential in basic science, developmental, cognitive and clinical studies of normal and impaired brain function. This proposal will reveal the fundamental limits of hemodynamic-based methods to image and detect brain function.

描述（由申请人提供）：拟议工作的目的是确定和表征由唤起神经活动引起的代谢和血液动力学反应的时空限制。为此，将使用表达光敏感蛋白通道蛋白2的遗传增强的小鼠模型，从而通过调节直径和直接传递到大脑表面的光刺激的强度来控制神经元活性（照片刺激）。首先，将使用具有亚微米计分辨率的两光子显微镜确定引起血流反应的最小神经元活性。使用钙指标将表征神经元活性的大小和强度。然后，将使用血管内荧光染料来测量毛细血管中血液速度和血管直径的相应变化。其次，这些发现的一致性和分辨率的效果将通过测量功能性脑血流，代谢和整体血液动力学反应，并使用较大规模的光学成像和分辨率分辨出数十微米。具体而言，以下光学方法将用于测量对神经活动的血流，代谢和总体血流动力学反应：激光斑点成像，内在自发荧光成像和内在信号的光学成像。后者是血液氧合水平依赖性功能磁共振成像的直接类似物（BOLD FMRI）。该项目的结果是，代谢和血液动力学反应的时空限制将通过无与伦比的分辨率进行发现。此外，将获得足够的知识，以阐明当前大脑研究工具（例如fMRI）的理论和实际要求，以检测在血液动力学反应中编码的活动，这些活动可能被认为是无法检测到的。这项工作将对动物和人类功能的大脑成像研究产生巨大影响，包括临床和基础科学研究。为了进行拟议的研究，我将在脑功能和互补的光学成像方法的两光子成像以及神经元活性的电生理记录中接受训练。本地和国家专家的独特组合将提供和监督必要的培训。该建议对于实现我的最终职业目标至关重要，即获得一个独立而成功的研究计划，该计划着重于成像正常和病理大脑功能。 公共卫生相关性：神经活动引起的血液动力学反应是研究动物和人类脑功能的主要手段。现在，功能性磁共振成像等方法在正常和脑功能受损的基础科学，发育，认知和临床研究中至关重要。该建议将揭示基于血液动力学的方法的基本限制，以形象和检测脑功能。