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 该BRG R01（PAR-16-242）申请旨在极大地改善空间和临时分辨率： 穿透电气模拟阵列是基本神经科学研究和人类的关键组成部分 神经假想。这项技术的挑战是实现相同的高度局部刺激区域 神经元数周和几个月。但是，皮质微电极的植入会导致反应性组织 响应，这会导致首选功能性能随着时间的推移而降级，从而限制了 设备功能。当前的电动仿真将束缚在头骨上，该颅骨长期增加 机械不匹配的影响会导致植入物周围的神经变性，增加了 感染，增加了机械创伤引起的失败以及电极移动的机会 位置，并增加神经胶质疤痕的电阻抗。反过来，电刺激失去了 激发神经元组织的有效性，使寿命成为挑战。简单地将电流增加到 补偿可以导致对组织和/或电极的允许损害。 该建议证明了一种创新的策略，该策略使用领先的生物相容性材料来开发 创新的“无线轴突”电极是超小型和不受限制的，具有生物活性表面和 纳米结构材料，以增强信号转导向电动组织。该项目旨在 解除传统微刺激技术所需的机械要求并改进 活化神经元的空间选择性用于稳定的长期电气模拟。指导假设是 将机械系绳解耦将改善组织的整合，而固定的生物分子将有效地 干预反应性组织反应以及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高级神经问题做出重大贡献 术语（永久），高质量和选择性神经刺激。这些可能导致范式变化 在神经科学研究和临床神经心理和神经刺激中， 长期激活特定神经元的能力，精确。我们的指导假设是 合并福利的产物是协同的，并且比其各个部分的总和更大。结果 该项目还可能建立新的以生物学启发的范例来创造持久的高保真性 具有仿生材料的神经界面以及纵向探测神经回路的新范式， 特别是为了学习学习和可塑性。该项目开发的技术的几种变体 预计将与光遗传学兼容。该项目将影响神经科学研究 社区和临床科学家（神经外科医生，神经科医生和患者）使用和受益 神经假体和神经刺激的治疗干预措施。