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; 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.

项目摘要 电微刺激已成为基本神经科学探索和 越来越普遍的临床疗法。尽管神经调节疗法的患病率越来越大 驱动患者有益效果的基本生理和机械特性差 理解。该R01应用程序旨在极大地提高我们对不同非神经元如何的理解 细胞（髓样谱系，少突胶质细胞祖细胞谱系和血管平滑肌细胞）反应 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性（包括血流）将有助于确定 随着时间的推移，对慢性电路行为的电微刺激。在此提案中，我们在 带有多个转基因动物的体内多光子成像技术，以系统地评估 刺激参数与分子，细胞和诱导的随时间变化之间的关系 本地网络。对电微刺激对整体组织的影响有了改进的理解 健康，外国身体反应的变化，组织修复的刺激以及安全限制将有助于告知 改善治疗应用和基本神经科学的刺激范例和设备设计 研究。