Wide deployment of massively multiplexed nanosystems for brain activity mapping

这个项目将把许多实验神经学家验证的、大规模多路复用的工具放在手中 用于记录神经元活动，用于神经调节剂的化学传感，以及用于高度图案化的光发生 同时进行电子记录的刺激--在大脑的任何区域。这将通过以下方式实现 利用两家PI与微芯片代工厂长达数十年的工作关系，实现神经产品的大规模生产 超大规模集成电路专用集成电路(“微芯片”)的纳米探头，以及支持用于 读出和控制。我们在技术开发中的最高目标是优化对最终目标的有用性 用户。我们将通过一个高度互动的程序来实现这一点：1)征求用户需求；2)组装和验证 活体神经纳米探针系统；3)为神经科学家部署完整的系统；4)提供技术支持 以提高最终用户使用新神经技术的成功；随后，征求反馈意见以 使连续几代神经技术的设计成为可能。 将生产和传播的技术基于PI经过验证的神经纳米探针和 先进的定制微芯片，用于读出和控制。我们现有的256通道纳米探针层模块 (组装成1,024个通道3D阵列)和微芯片由将用于 这一努力。这些系统已经在体内得到了验证。在Y1，纳米探针层模块将用 1024个频道，并将堆叠到具有10,240个全时/全带宽频道的复合3D系统中。 在Y2中，将批量生产具有8,192个通道的纳米探针层模块；这些模块将可堆叠配置 密度高的复合3D系统，具有约100,000个全时/全带宽通道。这头两次生产 启用电生理刺激、记录和神经化学传感系统。第三部作品 RUN将把光遗传刺激与近端多部位电生理记录结合起来。这些混血儿 纳米探针将包含512个用于光遗传刺激的e像素和512个近端记录电极。 这项新技术将在一开始就融入社会的不同需求，从而产生持久的影响。 使用这些电生理、神经化学和光遗传探针，八名热情的“阿尔法领养者” 将研究帕金森氏症等运动和情绪障碍背后的皮质和皮质下回路 大鼠模型中的疾病(Gradinaru Lab)；大脑皮层和环路的行为和计算作用 小鼠胡须系统(Bruno Lab)、小鼠视觉系统(Yuste Lab)和灵长类动物(Tolias Lab)； 人类患者的语言表征(Yvert Lab)；睡眠在记忆巩固中的作用(Laurent Lab) 神经元活动和能量供应之间的耦合(Magistretti Lab)；以及小鼠的口渴核 下丘脑(Oka Lab)。这些用户将提供直接反馈，以便在工作早期进行探头改进。 除了这些阿尔法采用者之外，感兴趣的最终用户将通过我们的 出版物，在我们网站上的帖子，在神经科学会议上的简短演讲，以及直接联系。

This project will place into the hands of many experimental neuroscientists validated, massively-multiplexed tools for recording of neuronal activity, for chemical sensing of neuromodulators, and for highly-patterned optogenetic stimulation with concurrent electrical recording – in any region of the brain. This will be accomplished by making use of both PIs' decades-long working relationship with microchip foundries, to enable mass production of neural nanoprobes, of VLSI application-specific integrated circuits (“microchips”), and of supporting instrumentation for read-out and control. Our paramount objective in technology development is to optimize usefulness for end- users. We will achieve this by a highly-interactive program that: 1) solicits user needs; 2) assembles and validates neural nanoprobe systems in vivo; 3) deploys complete systems to neuroscientists; 4) provides technical support to enhance the end-users' success with the new neurotechnology; and, subsequently, 5) solicits feedback to enable the design of successive generations of neurotechnology. The technology to be produced and disseminated is based upon the PI's validated neural nanoprobes and advanced, custom microchips for their readout and control. Our existing 256-channel nanoprobe layers modules (assembled into 1,024 channel 3D arrays) and microchips were fabricated by the foundries that will be used in this effort. These systems have been validated in vivo. In Y1, nanoprobe layer modules will be fabricated with 1,024 channels, and will be stackable into composite 3D systems with 10,240 full time/full bandwidth channels. In Y2 nanoprobe layer modules with 8,192 channels will be mass produced; these will be stackable to configure dense, composite 3D systems with ~100,000 full time/full bandwidth channels. These first two production runs enable systems for electrophysiological stimulation, recording, and neurochemical sensing. A third production run will integrate optogenetic stimulation with proximal multisite electrophysiological recording. These hybrid nanoprobes will contain 512 e-pixels for optogenetic stimulation and 512 proximal recording electrodes. This new technology will have lasting impact by incorporating diverse needs of the community at the outset. Using these electrophysiological, neurochemical, and optogenetic probes, eight enthusiastic “alpha adopters” will investigate cortical and subcortical circuitry underlying movement and mood disorders such as Parkinson's disease in rat models (Gradinaru Lab); the behavioral and computational roles of cortical layers and circuits in the mouse whisker system (Bruno Lab), visual systems in the mouse (Yuste Lab) and primates (Tolias Lab); speech representations in human patients (Yvert Lab); the role of sleep in memory consolidation (Laurent Lab); coupling between neuronal activity and energy supply (Magistretti Lab); and the thirst nucleus of the mouse hypothalamus (Oka Lab). These users will provide direct feedback to enable probe refinement early in the effort. Interested “beta” end-users, beyond these alpha adopters, will be recruited through solicitations in our publications, postings on our website, short talks at neuroscience conferences and by directly contact.