A Wireless, Closed-Loop Neural Probe for Optogenetics, Pharmacology and Neurochemical Monitoring

项目概要/摘要 包括光遗传学和药理学在内的新兴工具和技术提供了重要的途径 用于神经科学研究。然而，尽管工作紧张，但要实现闭环仍具有挑战性 以允许动物自由运动、多模式操作和多路复用的方式进行神经调节 以高灵敏度、选择性、时空分辨率和细胞特异性监测神经化学物质， 同步我们的长期目标是开发支持这些功能的先进工具和方法 用于神经系统的大规模调节和监测。我们的近期目标是发展无线， 闭环神经探针系统，用于光遗传学、药理学和神经化学监测， 移动老鼠和老鼠。我们将通过以下三个具体目标来实现这一目标： 用于选择性和灵敏地监测具有高时空的神经化学物质的软神经探针 分辨率和细胞特异性;（2）开发用于光遗传学的无线闭环神经探针， 药理学和神经化学监测;和（3）评估和表征效率和 在自由移动的小鼠和大鼠体内，无线闭环神经探针的功能性。拟议 研究是创新的五个关键原因：首先，适体增强的石墨烯场效应晶体管（AeG- G-FET）联合收割机将适体的高选择性与G-FET的高灵敏度相结合，从而使得灵敏的 （飞摩尔）和选择性（> 19倍）检测神经化学物质。第二，接近细胞尺度的维度 (50 AeG-FET的快速响应时间（~1 s）和位置选择性功能化使其能够 监测多种神经化学物质，包括多巴胺、血清素、去甲肾上腺素和神经肽Y， 时空分辨率、灵敏度和选择性。第三，将最先进的基因编码 带有无线荧光光度计的荧光传感器可以检测多种神经化学物质 在自由运动动物的遗传定义的神经元中。第四，多式联运和定制化的图形 用户界面（GUI）提供了一个强大的、易于使用的自动化数据分析和控制界面， 光遗传学和/或药理学操作，从而能够调节和按需 神经调节最后，磁共振耦合和无线数据通信允许完全无线， 无电池操作，从而实现轻量化结构并消除对电池寿命的担忧， 充电状态，以及在扩展行为测试期间经常出现的其他问题，而同时 允许动物自由活动。成功完成拟议的研究将产生无线，“所有- “一体化”闭环神经探针，具有用于神经化学监测的多项创新功能， 在自由移动行为期间的光遗传学和/或药理学刺激。我们相信这些神经探针 神经科学界对神经科学的基础研究以及 在与BRAIN倡议相关的各种背景下，

PROJECT SUMMARY/ABSTRACT Emerging tools and technologies, including optogenetics and pharmacology, have provided important avenues for neuroscience research. However, despite intensive work, it is still challenging to achieve closed-loop neuromodulation in a way that allows the free movement of animals, multimodal operation, and multiplexed monitoring of neurochemicals with high sensitivity, selectivity, spatiotemporal resolution, and cellular specificity, simultaneously. Our long-term goal is to develop advanced tools and approaches that support these capabilities for large-scale modulation and monitoring of the nervous system. Our immediate goal is to develop wireless, closed-loop neural probe systems for optogenetics, pharmacology, and neurochemical monitoring in freely moving mice and rats. We will achieve this goal by pursuing the following three specific aims: (1) to develop soft neural probes for the selective and sensitive monitoring of neurochemicals with high spatiotemporal resolution and cellular specificity; (2) to develop wireless, closed-loop neural probes for optogenetics, pharmacology, and neurochemical monitoring; and (3) to evaluate and characterize the efficiency and functionality of the wireless, closed-loop neural probes in vivo in freely moving mice and rats. The proposed research is innovative for five key reasons: First, the aptamer-enhanced graphene-field effect transistors (AeG- FETs) combine the high selectivity of the aptamer with the high sensitivity of G-FETs, thereby enabling sensitive (femtomolar) and selective (> 19-fold) detection of neurochemicals. Second, the nearly cellular-scale dimensions (50 μm x 50 μm), fast response time (~1 s), and site selective functionalization of AeG-FETs make it possible to monitor multiple neurochemicals, including dopamine, serotonin, norepinephrine, and neuropeptide Y, with high spatiotemporal resolution, sensitivity, and selectivity. Third, coupling state-of-the-art genetically encoded fluorescent sensors with a wireless multicolor photometer makes it possible to detect multiple neurochemicals in genetically defined neurons of freely moving animals. Fourth, multimodal operation and a customized graphical user interface (GUI) provide a robust, easy-to-use automated data analysis and control interface for closed-loop optogenetic and/or pharmacological manipulation, thereby enabling adjustable and on-demand neuromodulation. Finally, magnetic resonance coupling and wireless data communication allow fully wireless, battery-free operation, thereby enabling lightweight construction and eliminating concerns about battery life, charging status, and other issues that often arise during extended behavioral tests, while at the same time allowing animals to move freely. The successful completion of the proposed research will yield wireless, “all- in-one” closed-loop neural probes with several innovative features for neurochemical monitoring and optogenetic and/or pharmacological stimulation during freely moving behaviors. We believe these neural probes will be of great interest to the neuroscience community for basic studies in neuroscience as well as for studies of disease-related processes in various contexts relevant to the BRAIN initiative.