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

项目摘要 电微刺激已经成为基础神经科学探索的支柱， 越来越多的临床治疗。尽管神经调节疗法日益流行， 驱动对患者有益效果的基本生理和机械特性很差 明白这个R01应用程序的目的是大大提高我们对不同的非神经元细胞是如何产生的理解。 细胞（髓系、少突胶质细胞祖细胞系和血管平滑肌细胞）应答， 有助于电刺激反应。理解刺激与 参数和支持非神经元细胞活动，包括血流，将有助于确定 随着时间的推移，电微刺激对体内慢性回路行为的影响。在本提案中，我们使用前沿技术， 体内多光子成像技术与多个转基因动物，系统地评估 刺激参数与诱导的分子、细胞和细胞内变化之间的关系 本地网络。更好地理解电微刺激对整体组织的影响 健康、异物反应的变化、组织修复的刺激和安全限制将有助于告知 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 research.

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.