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执行的计算。实现这一目标的一个巨大障碍是--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，对脑组织造成太大的损伤。如果放置的密度足够高，可以对大多数神经元进行采样，那么它们将破坏它们想要监测的电路。理解大脑局部计算的另一个重要障碍是，电路动态会被化学神经调节剂迅速而显著地改变，而这种改变通常是无法观察到的。使用快速扫描循环伏安法可以实现对多巴胺等关键调节剂的实时监测，但这种方法尚未与大规模电路记录有效结合。 拟议的工作将在克服这些障碍方面取得重要进展，使用8微米碳丝电极的超密集阵列。它们足够坚硬，可以深入大脑，但又足够小，可以避免破坏性的免疫反应。通过在电极之间使用80微米的距离，皮质层内的绝大多数神经元将在记录范围内。此外，碳丝电极非常适合使用伏安法进行化学传感。该建议是在一系列模块化步骤中构建用于神经科学研究的先进新工具，最终在自由行为大鼠中实现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，该框架允许组装超密度阵列，以及更新的云台，允许同时监控数百个通道。目标2将利用碳丝电极在组织学处理过程中原位切片的能力。这极大地促进了在微电路架构内定位单个记录位点的能力，以及识别单个记录神经元的能力。目标3涉及进一步优化碳丝电极用于化学传感，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，该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，功能强大的设备，这些设备将被广泛传播，并可能对我们了解大脑如何工作产生变革性的影响。

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.