Subcellular Wireless Axons for in vivo Localized Neuronal Excitation

用于体内局部神经元兴奋的亚细胞无线轴突

• 批准号: 10534746
• 负责人: Takashi Daniel Yoshida Kozai
• 金额: $ 33.12万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10534746
• 关键词: Acute; Area; Autopsy; Axon; Basic Science; Benchmarking; Biocompatible Materials; Biomimetic Materials; Brain; Brain Injuries; Carbon Nanotubes; Cerebral cortex; Chronic; Cicatrix; Clinical; Communities; Compensation; Coupling; Data; Devices; Effectiveness; Electric Stimulation; Electrodes; Electrophysiology (science); Encapsulated; Failure; Foundations; Frequencies; Goals; Histologic; Human; Immobilization; Immune response; Implant; Infection; Inflammatory Response; Intervention; Lasers; Lateral; Learning; Light; Longevity; Maps; Measures; Mechanics; Methods; Microelectrodes; Microglia; Modality; Mus; Nanostructures; Nerve Degeneration; Neurologist; Neurons; Neurosciences Research; Neurosurgeon; Outcome; Patients; Penetration; Performance; Physiologic pulse; Population; Positioning Attribute; Probability; Property; Reaction; Reporter; Risk Reduction; Safety; Scientist; Signal Transduction; Structure; Sum; Surface; System; Technology; Testing; Time; Tissues; Trauma; Validation; Variant; Visualization; Width; biomaterial compatibility; cell type; cranium; design; electric impedance; electrical microstimulation; experience; experimental study; genetic manipulation; heat injury; implantation; improved; in vivo; innovation; light scattering; microstimulation; nervous system disorder; neural; neural circuit; neural implant; neural stimulation; neuron loss; neuroprosthesis; neuroregulation; neurotransmission; novel; novel strategies; optogenetics; response; success; temporal measurement; tool; wireless

Project Summary This BRG R01 (PAR-16-242) application aims to greatly improved spatial and temporal resolution: Penetrating electrical stimulation arrays are a crucial component of basic neuroscience research and human neuroprosthetics. A challenge with this technology is achieving a highly localized stimulated area of the same neurons over weeks and months. However, implantation of cortical microelectrodes causes a reactive tissue response, which results in a degradation of the preferred functional performance over time, thus limiting the device capabilities. Current electrical stimulation implants are tethered to the skull, which chronically increases the impact of mechanical mismatch, causes neural degeneration around the implant, increases the chance of infection, increases the chance of mechanical trauma induced failure as well as shifting of the electrode position, and increases in electrical impedances from glial scarring. In turn, the electrical stimulation loses its effectiveness to excite neural tissue, making longevity a challenge. Simply increasing the electrical current to compensate can lead to permenant damage to the tissue and/or the electrode. This proposal proves an innovative strategy that uses leading-edge biocompatible materials to develop innovative “Wireless Axon” electrodes that are ultra-small and untethered, with bioactive surfaces and nanostructured materials for enhanced signal transduction to electrically excitable tissue. The project aims to decouple the mechanical requirements necessary in traditional microstimulation technology and improve spatial selectivity of activated neurons for stable long-term electrical stimulation. The guiding hypothesis is that decoupling the mechanical tether will improve tissue integration, while immobilized biomolecules will effectively intervene with the reactive tissue response as well as improve electrode-neuron signal-coupling and selectivity. This project is likely to make significant contributions through developing advanced neural probes for long- term (permanent), high quality, and selective neural stimulation. These could potentially lead to paradigm shifts in both neuroscience research and clinical neuroprosthetics and neurostimulation through creating the capability of activating specific neurons for long periods of time with great precision. Our guiding hypothesis is that the product of the combined benefit is synergistic and greater than the sum of its parts. The outcomes of this project are also likely to establish new biologically inspired paradigms for creating long-lasting, high-fidelity neural interfaces with biomimetic materials as well as new paradigms for longitudinally probing neural circuits, particularly for the study of learning and plasticity. Several variations of the technology developed in this project is expected to be compatible with optogenetics. This project would impact both the neuroscience research community, and clinical scientists (neurosurgeons, neurologists, and patients) that use and benefit from neuroprosthetic- and neurostimulation-based treatments interventions.

项目摘要 此BRG R01(PAR-16-242)应用程序旨在大幅提高空间和时间分辨率： 穿透性电刺激阵列是基础神经科学研究和人类 神经假体。这项技术的一个挑战是实现高度局部化的相同刺激区域 几个星期和几个月的神经元。然而，植入皮质微电极会引起反应性组织 响应，这会导致首选功能性能随着时间的推移而下降，从而限制 设备功能。目前的电刺激植入物被拴在头骨上，这会慢性增加 机械失配的影响，导致植入物周围的神经退化，增加了 感染，增加了机械创伤导致的故障和电极移位的机会 位置，以及神经胶质瘢痕形成的电阻抗增加。反过来，电刺激失去了它的 有效地刺激神经组织，使长寿成为一个挑战。只需将电流增加到 补偿可能导致对组织和/或电极的永久性损害。 这一提议证明了一种创新战略，即使用尖端的生物兼容材料来开发 创新的“无线轴心”电极，超小且不系绳，具有生物活性表面和 用于增强对电可兴奋组织的信号传导的纳米结构材料。该项目旨在 分离传统微刺激技术中所需的机械要求，并改进 激活神经元对稳定的长期电刺激的空间选择性。指导性假设是 机械系绳的解偶联将改善组织整合，而固定的生物分子将有效 干预反应性组织反应，改善电极-神经元信号耦合和选择性。 这个项目很可能通过开发先进的神经探头来做出重大贡献。 长期(永久性)、高质量和选择性的神经刺激。这些可能会潜在地导致范式转变 在神经科学研究和临床神经假体和神经刺激方面，通过创造 能够以极高的精度长时间激活特定的神经元。我们的指导性假设是 综合效益的乘积是协同的，大于其各部分的总和。其结果是 该项目还可能建立新的生物启发范例，以创建持久、高保真的 神经与仿生材料的接口以及用于纵向探测神经电路的新范例， 尤其是对于学习和可塑性的研究。在这个项目中开发的技术的几个变种 预计将与光遗传学兼容。这个项目将对神经科学研究产生影响 社区和临床科学家(神经外科医生、神经病学家和患者)使用并受益于 基于神经假体和神经刺激的治疗干预。