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: 10668278
• 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/10668278
• 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; Proliferating; 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.

项目总结