Role of interneurons in brain tissue oxygen regulation

项目摘要 脑组织中氧的调节是脑组织中最重要的基本问题之一， 神经科学和医学。大脑具有高代谢需求及其健康功能 取决于将组织氧维持在相对较窄的范围内， 防止缺氧和低到足以最大限度地减少有毒氧物质的产生。调控 大脑皮层中的脑组织氧含量受兴奋性活动的影响，包括 丘脑皮质输入和锥体细胞，以及中间神经元的活动，但他们如何 对这一重要过程的形状仍知之甚少。根据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PO 2 自发波动和刺激诱发的反应，根据其程度的神经元 击发在目标1中，我们将证明中间神经元是PO 2调节和阻断所必需的。 中间神经元输出将导致与增加的神经元输出平行的降低的PO 2响应。 活动在目标2中，我们将确定中间神经元是否能够产生PO 2反应 没有兴奋性活动。在目标3中，我们将确定PO 2的振幅和频率 波动依赖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率（8-15 cpm）的PO 2波动。 同时进行血氧、MRI和电生理测量， 药理学操作以及感觉和光遗传学刺激将提供信息 脑组织氧气调节的理论这些研究将使人们更深入地了解 中间神经元的生理学以及它们如何塑造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.