Wide deployment of massively multiplexed nanosystems for brain activity mapping

这个项目将把许多实验神经科学家手中的验证， 用于记录神经元活动，用于神经调质的化学传感，以及用于高度模式化的光遗传学 同时进行电记录的刺激-在大脑的任何区域。这将通过使 利用两个PI与微芯片代工厂长达数十年的合作关系， 纳米探针、VLSI专用集成电路（“微芯片”）和用于测量的支持仪器的制造。 读出和控制。我们在技术开发中的首要目标是优化最终用途， 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 体内神经纳米探针系统; 3）为神经科学家部署完整的系统; 4）提供技术支持 提高最终用户对新神经技术的成功率;以及，随后，5）征求反馈， 能够设计出连续几代的神经技术。 生产和传播的技术是基于PI的验证神经纳米探针， 先进的定制微芯片来进行读取和控制。我们现有的256通道纳米探针层模块 （组装成1，024通道3D阵列）和微芯片由将用于 这种努力。这些系统已在体内得到验证。在Y1中，纳米探针层模块将用 1，024个通道，并可堆叠成具有10，240个全时/全带宽通道的复合3D系统。 在Y2中，将批量生产具有8，192个通道的纳米探针层模块;这些模块将可堆叠以配置 密集的复合3D系统，具有约100，000个全时/全带宽通道。前两次生产运行 使系统能够进行电生理刺激、记录和神经化学感测。第三生产 Run将光遗传学刺激与近端多位点电生理学记录整合。这些混合 纳米探针将包含用于光遗传学刺激的512个e像素和512个近端记录电极。 这项新技术将在一开始就结合社区的各种需求，产生持久的影响。 利用这些电生理学、神经化学和光遗传学探针，八位热情的“阿尔法采纳者” 将研究运动和情绪障碍（如帕金森氏症）背后的皮层和皮层下回路， 疾病大鼠模型（Gradinaru实验室）;行为和计算的作用，皮质层和电路， 小鼠胡须系统（Bruno Lab），小鼠视觉系统（Yuste Lab）和灵长类动物（Tolias Lab）; 人类患者的语音表征（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实验室）;以及小鼠的口渴核 下丘脑（Oka Lab）。这些用户将提供直接反馈，以便在工作的早期实现探测器的细化。 感兴趣的“测试版”最终用户，除了这些阿尔法采用者，将通过招标招募在我们的 出版物，我们网站上的帖子，神经科学会议上的简短演讲和直接联系。

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.