Fast Optical Imaging with Flavoprotein Autofluorescence in Visual Cortex

视觉皮层中黄素蛋白自发荧光的快速光学成像

• 批准号: 7286816
• 负责人: MITSUHIRO FUKUDA
• 金额: $ 17.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7286816
• 关键词: Active Sites; Animals; Architecture; Area; Autoradiography; Base of the Brain; Brain; Brain Mapping; Brain imaging; Cells; Clinical Research; Cognitive deficits; Coupled; Degenerative Disorder; Deoxyglucose; Diagnosis; Evaluation; Felis catus; Flavins; Flavoproteins; Functional Imaging; Goals; Hemoglobin; Human; Image; Individual; Laboratories; Localized; Maps; Measurement; Measures; Metabolic; Mitochondria; Modeling; Monitor; NADH; Neurons; Neurosciences; Nicotinamide adenine dinucleotide; Optics; Oxidation-Reduction; Oxygen Consumption; Oxygen measurement, partial pressure, arterial; Pattern; Personal Satisfaction; Photic Stimulation; Recording of previous events; Relative (related person); Research; Research Personnel; Resolution; Rodent; Scanning; Signal Transduction; Site; Specificity; Stimulus; Structure; System; Techniques; Testing; Tissues; Vision; Visual Cortex; area striata; base; charge coupled device camera; hemodynamics; human disease; improved; in vivo; millimeter; optical imaging; orientation columns; relating to nervous system; response; spatiotemporal; success

DESCRIPTION (provided by applicant): In this research, we will focus on spatial and temporal resolution of the autofluorescence signal induced by neural activity. Optical imaging of autofluorescence signal of mitochondrial endogenous flavoprotein can be used for monitoring spatial and temporal patterns of neural activity from a relatively large cortical area of the brain with high spatial and temporal resolution. Despite a long history of optical measurements of cellular autofluorescence and recent successful attempts of flavoprotein imaging in rodent cortex in vivo, application of this technique to phylogenetically higher animals and humans for functional brain mapping has been underestimated. The specific aim of this proposed research is to investigate the feasibility of flavoprotein autofluorescence imaging for functional brain mapping in phylogenetically higher animals' visual cortex whose functions are relevant to the human brain. Our long-term goal is to elucidate the spatiotemporal correlation between neuronal activity and their metabolic responses induced by stimulation, and inherent spatial and temporal resolution of the metabolic-based functional brain imaging. The specific hypotheses to be tested are: 1) neural activity-dependant metabolic change detected by flavoprotein autofluorescence signal is highly confined to neural active sites, and 2) the flavin autofluorescence signal immediately emerges after the onset of stimulation. We base these hypotheses on general observations that i) a stimulus-induced increase in gluclose utilization is well localized to neural active sites and that ii) a stimulus- induced tissue oxygen tension change is tightly correlated with neural spiking activity. We will test these hypotheses on the model of orientation columns in the primary visual cortex. The orientation column is a functional structure related to stimulus orientation, in which neurons in response to the same orientation cluster together and form columns through pia to white mater, and it has been extensively investigated electrophysiologically, anatomically, and with hemodynamic-based optical imaging of intrinsic signals. The orientation maps obtained from flavoprotein signal will be quantitatively compared to the maps of the well- established hemodynamic-based intrinsic signals for its evaluation. We believe that the establishment of this technique will greatly improve the acuracy of mapping neural activity which will provide cruicial information for diagnosis and treatment of disease and human brain functions.

描述（由申请人提供）： 在本研究中，我们将集中在空间和时间分辨率的自发荧光信号诱导的神经活动。线粒体内源性黄素蛋白的自发荧光信号的光学成像可用于以高空间和时间分辨率监测来自大脑的相对大的皮质区域的神经活动的空间和时间模式。尽管细胞自发荧光的光学测量和最近的成功尝试在啮齿动物皮层在体内的黄素蛋白成像的历史悠久，这种技术的应用程序遗传学高等动物和人类的功能脑映射一直被低估。这项拟议研究的具体目的是研究黄蛋白自发荧光成像用于系统发育高等动物视觉皮质功能脑映射的可行性，其功能与人类大脑相关。我们的长期目标是阐明神经元活动与刺激诱导的代谢反应之间的时空相关性，以及基于代谢的脑功能成像的固有空间和时间分辨率。待检验的具体假设是：1）通过黄素蛋白自体荧光信号检测的神经活性依赖性代谢变化高度局限于神经活性位点，以及2）黄素自体荧光信号在刺激开始后立即出现。我们将这些假设基于以下一般观察：i）刺激诱导的葡萄糖利用的增加很好地定位于神经活性位点，以及ii）刺激诱导的组织氧张力变化与神经尖峰活动紧密相关。我们将在初级视觉皮层的方向柱模型上检验这些假设。定向柱是一种与刺激定向相关的功能结构，其中响应于相同定向的神经元聚集在一起并形成穿过软脑膜到白色脑膜的柱，并且已经从电生理学、解剖学和基于血流动力学的内在信号光学成像方面对其进行了广泛的研究。将从黄素蛋白信号获得的方向图与基于血流动力学的固有信号的图进行定量比较，以进行评价。我们相信，该技术的建立将大大提高神经活动映射的准确性，为疾病的诊断和治疗以及人类大脑功能提供重要信息。