Maximizing flexibility: Optimized neural probes and electronics for long term, high bandwidth recordings

大脑是一个由大量相互连接的专门电路组成的网络。这些电路的三个特点 使它们特别具有挑战性：时间尺度的多样性、空间尺度的多样性和异质性。 因此，理解大脑需要跨越这些时间和空间尺度，并提供信息 关于细胞类型。我们需要能够记录单个神经元随时间的活动，以了解活动 毫秒时间尺度上的模式，以及这些模式如何随着经验的发展而在几小时、几天、几个月 甚至几年。我们需要能够记录整个皮质区域，跨越大脑的不同部分 区域以及所有层，以了解本地和分布式信息处理。我们也需要成为 能够将这些密集且分散的记录与成像相结合，以利用互补的 电气和光学测量的优势。这受到多重挑战的阻碍：1)当前的方法 缺乏检查三维或分布式所需的空间范围(跨越多个结构 详细介绍了网络。2)目前的电生理方法(提供毫秒级的分辨率) 通常缺乏遵循长期动态所需的寿命。3)电流电生理方法 使用不适合用于成像技术的刚性电极。这个项目的总体目标是 优化一套可以为社区应对这些挑战的补充技术，并使 它们已准备好供神经科学界普遍使用。我们的中心假设是我们最近 开发的纳米电子线(NET)设备，已显示出生物兼容性，体内功能 寿命长、高质量的单元记录以及与光学方法的兼容性是潜在的理想候选 了解大脑活动的模式。我们计划开发一系列精选的网络探头和高密度阵列 适用于不同香料中的多个大脑区域。我们将聘请专业的神经学家，让我们 开发和优化跨越小鼠、大鼠和绒猴的网络，并加快交付 将由此产生的技术带给科学界。我们将追求以下三个具体目标：1)优化 Net探针用于不同的大脑区域和物种；2)优化用于高密度区域和 分布式记录；以及3)确定适合每个物种和大脑区域的最佳设备。该方法 是创新的，因为我们将开发并投入普遍使用的技术具有推动 整个领域的创新，使新的、非常高密度的记录研究成为可能，并允许调查人员 以前所未有的细节和持续时间跟踪大型神经元集合。

The brain is a massively interconnected network of specialized circuits. Three characteristics of these circuits make them particularly challenging: diversity of time scales, diversity of spatial scales, and heterogeneity. Understanding the brain therefore requires spanning these temporal and spatial scales and providing information about cell-types. We need to be able to record the activity of individual neurons across time to understand activity patterns on a millisecond timescale and how those patterns evolve with experience across hours, days, months and even years. We need to be able to record throughout a cortical region, spanning both different parts of the region as well as all layers, to understand both local and distributed information processing. We also need to be able to combine these dense and distributed recordings with imaging to take advantage of the complementary strengths of electrical and optical measurements. This is hindered by multiple challenges: 1) Current approaches lack the spatial extent (spanning multiple structures) required to examine three-dimensional or distributed networks in detail. 2) Current electrophysiological approaches (which do provide the millisecond resolution) typically lack the necessary lifetime to follow long-term dynamics. 3) Current electrophysiological approaches use rigid electrodes that are ill-suited to use with imaging techniques. The overall objective of this project is to optimize a suite of complementary technologies that can address these challenges for the community and make them ready for common use by the neuroscience community. Our central hypothesis is that our recently developed nanoelectronic thread (NET) devices, which have demonstrated biocompatibility, in vivo function longevity, high quality unit recording and compatibility with optical methods, are a potentially ideal candidate for understanding patterns of brain activity. We plan to develop a selection of NET probes and high-density arrays that are suitable for multiple brain regions in different spices. We will engage expert neuroscientists, allowing us to develop and optimize NETs that work across mouse, rat and marmoset, and to expedite the delivery of resulting technologies to the scientific community. We will pursue the following three specific aims: 1) To optimize NET probes for various brain regions and species.; 2) To optimize NET probes for high-density regional and distributed recordings; and 3) To determine the best devices for each species and brain regions. The approach is innovative, because the technology we will develop and put into common use has the potential to drive innovation throughout the field, enabling new, very high density recording studies and allowing investigators to track large ensembles of neurons in unprecedented details and time duration.