Role of interneurons in brain tissue oxygen regulation

项目总结 脑组织中氧的调节是最重要的基础性问题之一。 神经科学和医学。大脑有很高的新陈代谢需求和健康的功能 取决于将组织氧气维持在一个相对较窄的范围内，该范围足够高到 防止缺氧，并足够低，以最大限度地减少有毒氧气物种的产生。这项规定 大脑皮质中的脑组织氧含量受兴奋性活动的影响，包括 丘脑皮质传入和锥体细胞，以及中间神经元的活动，但它们如何 塑造这一至关重要的过程仍然知之甚少。基于已公布的和初步的数据 我们假设中间神经元主要负责调节脑组织的氧分压。 自发波动和刺激诱发反应与其神经元程度的关系 开火。在目标1中，我们将展示PO2调节和阻断所需的中间神经元。 神经元间输出将导致PO2反应降低，同时神经元增加 活动。在目标2中，我们将确定中间神经元是否能够产生PO2反应 没有兴奋性活动。在目标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动 中间神经元主要负责高频(8-15cpm)的PO2波动。 同时进行氧气、核磁共振和电生理测量，并结合定位 药物操作以及感官和光遗传刺激将提供信息 关于脑组织的氧气调节。这些研究将使我们更深入地了解 中间神经元的生理学以及它们如何影响脑组织中的氧气水平。

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.