Subcellular Wireless Axons for in vivo Localized Neuronal Excitation

项目摘要 此BRG R 01（PAR-16-242）应用旨在大大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健康的重要组成部分。 神经修复术这种技术的挑战是实现相同的高度局部化的刺激区域。 神经元的数量。然而，植入皮质微电极会引起反应性组织 响应，这导致优选的功能性能随时间推移而退化，从而限制了 设备能力。目前的电刺激植入物被拴在头骨上， 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，增加了机械创伤引起的故障以及电极移位的机会 位置，并增加电阻抗神经胶质瘢痕。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。简单地增加电流， 补偿可能导致对组织和/或电极的永久性损伤。 该提案证明了一种创新策略，即使用领先的生物相容性材料来开发 创新的“无线Axon”电极，超小且无束缚，具有生物活性表面， 纳米结构材料，用于增强到电可兴奋组织的信号传导。该项目旨在 分离传统微刺激技术中必要的机械要求并改进 激活神经元对稳定长期电刺激的空间选择性。指导性假设是， 将机械系链解耦将改善组织整合，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先进的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。这些可能会导致范式转变 在神经科学研究和临床神经修复学和神经刺激方面， 具有长时间精确激活特定神经元的能力。我们的指导假设是 综合效益的乘积是协同的，大于其各部分的总和。的成果 这个项目也可能建立新的生物启发的范例，创造持久，高保真， 具有仿生材料的神经接口以及用于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。该项目开发的技术的几种变体 有望与光遗传学兼容。这个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）使用并受益于 基于神经假体和神经刺激的治疗干预。

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.