Using Electrical Stimulation to Modulation Microglia and the Conversion of Microglia Phenotypes

项目摘要 电微刺激已成为基础神经科学探索的支柱和 日益盛行的临床治疗。尽管神经调节疗法日益流行，但 对患者产生有益效果的基本生理和机械特性较差 明白了。此R01应用程序旨在极大地提高我们对非神经元 细胞(髓系、少突胶质祖细胞系和血管平滑肌细胞)反应和 有助于电刺激反应。对刺激之间关系的认识 参数和支持非神经细胞活动，包括血流，将有助于确定 电微刺激对体内慢性回路行为随时间的变化。在本提案中，我们使用了领先的 多转基因动物活体多光子成像技术系统评价 刺激参数与分子、细胞和细胞的诱导变化之间的关系 本地网络。更好地了解电微刺激对整个组织的影响 健康、异物反应的改变、组织修复的刺激和安全限度将有助于告知 用于治疗应用和基础神经科学的改进的刺激范例和装置设计 研究。

Project Summary Electrical microstimulation has become a mainstay of fundamental neuroscience exploration and an increasingly prevalent clinical therapy. Despite the growing prevalence of neuromodulation therapies, the fundamental physiological and mechanistic properties driving the beneficial effect for the patient are poorly understood. This R01 application aims to greatly improve our understanding of how different non-neuronal cells (myeloid lineage, oligodendrocyte progenitor lineage, and vascular smooth muscle cells) respond and contribute to the electrical stimulation response. Understanding of the relationship between stimulation parameters and supporting non-neuronal cell activity, including blood flow, will help determine the impact of electrical microstimulation on chronic circuit behavior in-vivo over time. In this proposal, we use leading-edge in vivo multiphoton imaging techniques with multiple transgenic animals to systematically evaluate the relationship between stimulation parameters and the induced changes over time at the molecular, cellular, and local network. An improved understanding of the impact of electrical microstimulation on the overall tissue health, changes to the foreign body response, stimulation of tissue repair, and safety limits will help inform improved stimulation paradigms and device design for therapeutic applications and basic neuroscience research.