Role of interneurons in brain tissue oxygen regulation

中间神经元在脑组织氧调节中的作用

• 批准号: 10409799
• 负责人: Daniil Aksenov
• 金额: $ 31.07万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409799
• 关键词: Brain; Brain Hypoxia; Cerebral cortex; Data; Electrodes; Electrophysiology (science); Ensure; Frequencies; Functional Magnetic Resonance Imaging; Generations; Halorhodopsins; Homeostasis; Hyperoxia; Hypoxia; Interneurons; Magnetic Resonance Imaging; Measurement; Measures; Medicine; Metabolic; Methods; Mus; Neurons; Neurosciences; Oryctolagus cuniculus; Output; Oxygen; Pathologic; Pharmacology; Physiology; Process; Publishing; Pyramidal Cells; Regulation; Role; Sensory; Shapes; Signal Transduction; Stimulus; Testing; Tissues; Vascular Diseases; Vibrissae; awake; barrel cortex; base; blood oxygenation level dependent response; brain tissue; cerebrovascular; improved; neuroimaging; optogenetics; pressure; prevent; response

PROJECT SUMMARY The regulation of oxygen in brain tissue is one of the most important fundamental questions in neuroscience and medicine. The brain has high metabolic demands and its healthy function depends on maintaining tissue oxygen within a relatively narrow range that is sufficiently high to prevent hypoxia and low enough to minimize generation of toxic oxygen species. The regulation of brain tissue oxygen in the cerebral cortex is influenced by excitatory activity, consisting of thalamocortical input and pyramidal cells, as well as the activity of interneurons, yet how they shape this vital process remains poorly understood. Based on published and preliminary data we hypothesize that interneurons are primarily responsible for regulating brain tissue PO2 spontaneous fluctuations and stimulus-evoked responses according to their degree of neuronal firing. In Aim 1, we will show that interneurons are required for PO2 regulation and blocking interneuron output will result in decreased PO2 response in parallel with increased neuronal activity. In Aim 2, we will determine whether interneurons are able to generate PO2 response without excitatory activity. In Aim 3, we will establish that the amplitude and frequency of PO2 fluctuations depend on inhibitory and excitatory spontaneous neuronal activity by demonstrating that interneurons are primarily responsible for high-frequency (8-15 cpm) PO2 fluctuations. Simultaneous oxygen, MRI, and electrophysiological measurements combined with localized pharmacological manipulations and sensory and optogenetic stimulation will provide information about brain tissue oxygen regulation. These studies will provide a deeper understanding of the physiology of interneurons and how they shape the oxygen level in brain tissue.

项目摘要 脑组织中氧气的调节是最重要的基本问题之一 神经科学和医学。大脑的代谢需求很高及其健康功能 取决于在相对狭窄的范围内维持组织氧，该范围足够高至 预防缺氧和足够低以最大程度地减少有毒氧的产生。法规 大脑皮层中脑组织氧的氧气受兴奋活动的影响，由 丘脑皮质输入和锥体细胞，以及中间神经元的活性，但如何 塑造这一重要过程仍然知之甚少。根据已发布和初步数据 我们假设中间神经元主要负责调节脑组织PO2 根据其神经元的程度，自发波动和刺激诱发的反应 射击。在AIM 1中，我们将证明中间神经元是PO2调节和阻塞所必需的 内神经元输出将导致PO2响应与神经元的增加同行 活动。在AIM 2中，我们将确定中间神经元是否能够产生PO2响应 没有兴奋活动。在AIM 3中，我们将确定PO2的幅度和频率 波动取决于抑制性和兴奋性自发神经元活性 该中间神经元主要负责高频（8-15 cpm）PO2波动。 同时氧气，MRI和电生理测量与局部结合 药理操作以及感觉和光遗传刺激将提供信息 关于脑组织氧气调节。这些研究将对 中间神经元的生理学及其如何塑造脑组织中的氧气水平。