Carbon Thread Arrays for High Resolution Multi-Modal Analysis of Microcircuits

描述（由申请人提供）：神经科学的一个主要目标是了解局部脑回路进行的计算。实现这一目标的一大障碍是——至少在哺乳动物中——我们目前无法观察到回路中大多数神经元的尖峰活动。一个关键原因是标准电极太大了，对脑组织造成了太大的损伤。如果放置在足够高的密度以对大多数神经元进行采样，它们将破坏它们打算监测的电路。理解局部大脑计算的另一个重要障碍是，化学神经调节剂会迅速而显著地改变电路动力学，而这通常是不被观察到的。使用快速扫描循环伏安法可以实现对多巴胺等关键调制剂的实时监测，但这种方法尚未有效地与大规模电路记录相结合。这项工作将在克服这些障碍方面取得重要进展，使用超密集的8微米碳线电极阵列。它们足够坚硬，可以植入大脑深处，但又足够小，可以避免破坏性的免疫反应。电极间距为80µm时，皮质层内的绝大多数神经元都在记录范围内。此外，碳线电极非常适合使用伏安法进行化学传感。本研究旨在通过一系列模块化步骤构建先进的神经科学研究新工具，最终在自由行为的大鼠中建立1024通道，结合电生理和电化学记录。目标1涉及硅框架的开发和测试，该框架允许超密集阵列的组装，以及允许同时监控数百个通道的更新前置台。目的2将利用碳线电极在组织学处理过程中被原位切片的能力。这极大地促进了在微电路结构中定位单个记录位点和识别单个记录神经元的能力。目标3涉及进一步优化用于化学传感的碳线电极，以及同时跨多个电极的联合单单元记录和快速扫描循环伏安法。总的来说，这个项目结合了电气工程、神经生理学和神经化学方面的专业知识，创造了创新的、强大的设备，这些设备将被广泛传播，并可能对我们对大脑工作方式的理解产生革命性的影响。

DESCRIPTION (provided by applicant): A major goal in neuroscience is to understand the computations performed by local brain circuits. A large obstacle to achieving this goal is that - at least in mammals - we currently cannot observe the spiking activity of most neurons within a circuit. A key reason is that standard electrodes are just too big, and provoke too much damage to brain tissue. If placed with high enough density to sample a majority of neurons, they would destroy the very circuit they are intended to monitor. Another important obstacle to understanding local brain computations is that circuit dynamics are rapidly and dramatically altered by chemical neuromodulators, which normally go unobserved. Real-time monitoring of critical modulators such as dopamine can be achieved using fast-scan cyclic voltammetry, but this method has not yet been effectively combined with large-scale circuit recordings. The proposed work would make important progress towards overcoming these obstacles, using ultra-dense arrays of 8µm carbon thread electrodes. These are stiff enough to insert deep into the brain, yet small enough to avoid a destructive immune response. By using an 80µm distance between electrodes, the great majority of neurons within a cortical layer would be within recording range. Furthermore, carbon thread electrodes are well-suited for chemical sensing using voltammetry. This proposal is to construct advanced new tools for neuroscientific investigation in a series of modular steps, culminating in 1024-channel, combined electrophysiological and electrochemical recording in freely-behaving rats. Aim 1 involves the development and testing of silicon frameworks that allow assembly of ultra-dense arrays, together with updated headstages that allow hundreds of channels to be monitored simultaneously. Aim 2 will exploit the ability of carbon thread electrodes to be sliced in situ during histological processing. This greatly facilitates the ability to localize individual recordig sites within microcircuit architecture, and to identify individual recorded neurons. Aim 3 involves further optimization of carbon thread electrodes for chemical sensing, and joint single-unit recording and fast-scan cyclic voltammetry across many electrodes simultaneously. Overall this project combines expertise in electrical engineering, neurophysiology, and neurochemistry to create innovative, powerful devices that will be widely disseminated and may have transformational impact for our understanding of how our brains work.