Mechanisms of Oligodendrocyte Activity on Chronic Brain Implants and Recording Performance

项目摘要 这项R 01（PA-20-185）应用旨在大大提高对少突胶质细胞的基础科学理解 关于长期植入的微电极和长时间植入的微电极周围的时空动态变化， 记录性能。穿透式记录微电极阵列是 大量的人类神经修复术获得选择性的、高保真的、持久的大脑活动读数是一种 影响运动、前运动和视觉皮质的基础和应用神经科学的关键技术 神经假体和脑机接口。然而，植入皮层微电极会导致 反应性组织反应，导致首选功能性单体性能下降 从而限制了设备的能力。虽然血脑屏障和其他胶质细胞如小胶质细胞和 长期以来，人们一直在研究星形胶质细胞对慢性记录性能的退化、 少突胶质细胞和少突胶质细胞祖细胞在这种异物反应中的作用尚未得到充分研究。 本建议旨在描述少突胶质细胞的作用和慢性记录失败在体内引起的 通过量化结构、细胞和分子水平的组织对慢性植入物的反应， 通过结合多光子成像技术和神经工程技术， 匹兹堡大学动态了解接口对于阐明 神经记录失败背后的机制。少突胶质细胞和少突胶质祖细胞具有 在脑损伤和许多神经退行性疾病后， 疾病因此，我们将利用在少突胶质细胞中具有特异性活性指标的转基因动物， 以及针对少突胶质细胞的药物和神经胶质调节方法， 改善少突胶质细胞健康和慢性皮质内记录性能的机制。这项工作 具有输出与神经工程，缺血， 中风、皮质内出血、动脉瘤、创伤性脑损伤、MS、ALS和闭环神经刺激。

Project Summary This R01 (PA-20-185) application aims to greatly improve basic science understanding of oligodendrocytes with respect to spatial and temporal dynamic changes around chronically implanted microelectrodes and long- term recording performance. Penetrating recording microelectrode arrays are a crucial component of numerous human neuroprosthetics. Obtaining selective, high fidelity, long-lasting readouts of brain activity is a critical technology across basic and applied neuroscience that impacts motor, pre-motor, and visual cortex neuroprostheses and brain-computer interfaces. However, implantation of cortical microelectrodes causes a reactive tissue response, which results in a degradation of the preferred functional single-unit performance over time, thus limiting the device capabilities. While the BBB and the role of other glial cells like microglia and astrocytes have long been studied with respect to the degradation of chronic recording performance, the role of oligodendrocytes and oligodendrocyte progenitor in this foreign body response has been understudied. This proposal aims to characterize the role of oligodendrocytes and chronic recording failure in vivo caused by the insertion via quantifying structural, cellular, and molecular level tissue response to chronic implants in the brain in real time through combining multiphoton imaging technology and neural engineering technology at the University of Pittsburgh. A dynamic understanding of the interfaces is necessary for elucidating the mechanism(s) behind neural recording failure. Oligodendrocytes and oligodendrocyte progenitor cells have been implicated as key players in neuronal health following brain injury and numerous neurodegenerative diseases. Therefore, we will utilize transgenic animals with specific activity indicators in oligodendrocytes as well as pharmaceutical and gliomodulation approaches that target oligodendrocytes in order to explore mechanisms that improve oligodendrocyte health and chronic intracortical recording performance. This work has the potential to output basic and clinical science level knowledge relevant to neural engineering, ischemia, stroke, intracortical hemorrhage, aneurysm, traumatic brain injury, MS, ALS, and closed-loop neurostimulation.