A Nanoelectronic Strategy for Reliable Chronic Neural Recording

在时间尺度上具有足够的时间分辨率，能够可靠地检测和跟踪单个神经元 与学习和记忆相称的是基础和转化神经科学的关键。长期 植入的神经电极构成了与低于100摄氏度的活体大脑进行电交互的唯一手段。 毫秒时间尺度和单神经元分辨率，但遭受持续的接口退化， 在短期和长期内，记录条件都发生了实质性的变化。人们越来越意识到 解决神经探针的尺寸和机械性能可以改善界面。然而，在这方面， 神经探针提供长时间的可靠记录，而没有慢性有害影响， 对器械的耐用性和生物相容性有严格的要求，但仍有待开发。 本项目的总体目标是实现稳定的组织-探针界面和可靠的电记录 通过开发，测试和优化纳米电子线（NET）神经探针。这将由以下人员进行研究： 广泛的体外表征和啮齿类动物模型（小鼠和大鼠）体内，其中组织探针 界面和神经探针记录条件将在长期植入过程中进行监测和评价 持续时间。将对植入探针附近的细胞和血管演变进行重复体内成像， 结合尸检组织学研究和慢性 记录性能以评估和优化NET探测器的功能。的中心假设 根据申请人实验室强有力的初步数据，该项目长期可靠 通过匹配神经探针，可以实现具有非降解组织-探针界面的电记录 物理性能，特别是尺寸、手术足迹和机械灵活性， 活体大脑中的细胞网络具体的目的是检验这一假设：1）设计和优化NET 用于长期体内结构稳定性的探针; 2）评估和优化 NET探针;以及3）验证和优化单个神经元的长期可靠记录和跟踪。的 申请人认为，这种方法是创新的，因为它代表了一种新的实质性的背离， 通过专注于积极减少神经记录的维度和刚性来改变现状 将这些设备引入以前无法实现的制度。本项目的长期目标是确定关键设计 参数，使人造设备和活脑组织之间的长期稳定整合， 这些参数可用于指导各种神经植入物的设计， 基础神经科学和有益的神经疾病治疗。前所未有的慢性 可靠性和稳定性的电气记录预计将实现在这个项目中也将导致大量的 脑机接口的改进可以应用于神经修复术。

The ability to reliably detect and track individual neurons with sufficient temporal resolution in time scale commensurate with learning and memory is critical to both basic and translational neurosciences. Chronically implanted neural electrodes constitute the only means to electrically interact with living brains at sub- millisecond time scale and single neuron resolution, but suffer from persistent interface degradation that leads to substantial recording condition changes in both the short and long term. There is a growing awareness that addressing the dimension and mechanical properties of the neural probe might improve the interface. However, neural probes that provide reliable recording for extended periods with no chronic detrimental effects pose stringent requirement on the robustness and bio-compatibility of the device, which are yet to be developed. The overall objective of this project is to achieve stable tissue-probe interface and reliable electrical recording by developing, testing and optimizing nanoelectronic thread (NET) neural probes. This will be studied by extensive in vitro characterization and in vivo in rodent models (mouse and rat) where the tissue-probe interface and the neural probe recording conditions will be monitored and evaluated over chronical implantation durations. Repeated in vivo imaging of the cellular and vascular evolution near the implanted probes will be used together with postmortem histology studies and comprehensive characterization of the chronical recording performance to assess and optimize the functionality of NET probes. The central hypothesis of the project, on the basis of strong preliminary data from the applicant's laboratory, is that chronically reliable electrical recording with non-degrading tissue-probe interface can be achieved by matching the neural probe physical properties, in particular the dimensions, the surgical footprint and the mechanical flexibility, with that of the cellular networks in living brain. The specific aims are to test this hypothesis: 1) Design and optimize NET probes for long-term in-vivo structural stability; 2) Evaluate and optimize the long-term biocompatibility of the NET probes; and 3) Verify and optimize long-term reliable recording and tracking of individual neurons. The approach is innovative, in the applicants' opinion, because it represents a new and substantive departure from the status quo by focusing on the aggressive reduction of the dimension and rigidity of the neural recording devices into previously unattainable regimes. The long-term goal of this project is to identify key design parameters that enable chronically stable integration between man-made devices and living brain tissue so that these parameters can be applied to guide the design of a variety of neural implants for advancing fundamental neuroscience and benefitting neurological condition treatments. The unprecedented chronic reliability and stability in electrical recording expected to be achieved in this project will also lead to substantial improvement in the brain-machine interface that can be applied to neuroprosthetics.