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.

项目概要 该 BRG R01 (PAR-16-242) 应用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科学研究的重要组成部分 这项技术的一个挑战是实现相同的高度局部化的刺激区域。 然而，皮层微电极的植入会导致组织产生反应。 响应，这会导致首选功能性能随着时间的推移而下降，从而限制了 目前的电刺激植入物被拴在头骨上，头骨会长期增加。 机械不匹配的影响，导致植入物周围的神经退化，增加了 感染，增加机械创伤引起的故障以及电极移位的机会 位置，并且神经胶质疤痕导致电阻抗增加，反过来，电刺激失去作用。 有效地刺激神经组织，使寿命成为一个挑战，只需增加电流即可。 补偿可能导致组织和/或电极永久性损坏。 该提案证明了一种创新策略，利用领先的生物相容性材料来开发 创新的“无线轴突”电极超小且不受束缚，具有生物活性表面和 该项目旨在增强可电兴奋组织的信号转导的纳米结构材料。 解耦传统微刺激技术中必要的机械要求并改进 激活神经元的空间选择性以实现稳定的长期电刺激。 解耦机械系绳将改善组织整合，而固定的生物分子将有效地 干预反应性组织反应并改善电极-神经元信号耦合和选择性。 该项目可能会通过开发长期的先进神经探针做出重大贡献。 长期（永久）、高质量和选择性神经刺激可能会导致范式转变。 通过创建神经科学研究和临床神经修复术和神经刺激 我们的指导性假设是长时间、高精度地激活特定神经元的能力。 综合效益的产物是协同的，并且大于其各个部分的总和。 该项目还可能建立新的受生物学启发的范例，以创造持久、高保真的效果 与仿生材料的神经接口以及纵向探测神经回路的新范例， 特别是对于学习和可塑性的研究。该项目中开发的技术的几种变体。 预计该项目将与光遗传学兼容。 使用并受益于的社区和临床科学家（神经外科医生、神经科医生和患者） 基于神经修复和神经刺激的治疗干预。