Elucidating electrical stimulation induced non-neuronal activity using emerging in vivo imaging technology and electrophysiology

利用新兴的体内成像技术和电生理学阐明电刺激诱导的非神经元活动

• 批准号: 10447133
• 负责人: Takashi Daniel Yoshida Kozai
• 金额: $ 61.41万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10447133
• 关键词: 2' ,3' -Cyclic-Nucleotide Phosphodiesterases; Astrocytes; Automobile Driving; Basic Science; Behavior; Biology; Biophysics; Blood Vessels; Blood flow; Brain; Calcium; Cell Differentiation process; Cell Lineage; Cells; Charge; Chemicals; Chronic; Clinical; Coupled; Databases; Degenerative Disorder; Development; Device Designs; Disease; DsRed; Electric Stimulation; Electrodes; Electrophysiology (science); Event; Foreign Bodies; Frequencies; Future; Health; Health Status; Image; Imaging Techniques; Imaging technology; Immune; Immunohistochemistry; Injury; Intervention; Investigation; Mental Depression; Microelectrodes; Microglia; Molecular; Monitor; Morphology; Mus; Myelogenous; Nerve Regeneration; Neuroglia; Neurons; Neurosciences; Neurosciences Research; Oligodendroglia; Optics; Parkinson Disease; Patients; Pericytes; Periodicity; Personal Satisfaction; Phase; Photic Stimulation; Physiological; Prevalence; Property; Protein Analysis; RNA analysis; Recommendation; Regenerative Medicine; Research; Safety; Sensory; Signal Transduction; Smooth Muscle Myocytes; Spectrum Analysis; Stimulus; Supporting Cell; Techniques; Therapeutic; Time; Tissues; Transgenic Animals; Vascular Smooth Muscle; Vasodilation; Visual Cortex; Work; angiogenesis; brain cell; brain tissue; clinical application; clinical implementation; design; electric impedance; electrical microstimulation; excitotoxicity; imaging approach; imaging platform; implantable device; implantation; improved; in vivo; in vivo imaging; microstimulation; multiphoton imaging; myelination; neural network; neuronal excitability; neuroregulation; neurovascular coupling; oligodendrocyte progenitor; predictive modeling; progenitor; ratiometric; response; sensor; spatiotemporal; stem cells; tissue repair; vasoconstriction; voltage

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.

项目概要 电微刺激已成为基础神经科学探索的支柱和 临床治疗日益普及。尽管神经调节疗法越来越流行， 对患者产生有益作用的基本生理和机械特性很差 明白了。这个 R01 应用程序旨在极大地提高我们对不同非神经元如何 细胞（骨髓细胞系、少突胶质细胞祖细胞系和血管平滑肌细胞）做出反应并 有助于电刺激反应。了解刺激之间的关系 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电路行为的影响。在这个提案中，我们使用了领先的技术 体内多光子成像技术对多种转基因动物进行系统评估 刺激参数与分子、细胞和神经系统随时间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体组织的影响 健康状况、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 改进治疗应用和基础神经科学的刺激范例和设备设计 研究。