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

用于微电路高分辨率多模态分析的碳线阵列

• 批准号: 9328183
• 负责人: JOSHUA D BERKE
• 金额: $ 84.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9328183
• 关键词: Action Potentials; Address; Affect; Architecture; Award; Beds; Behavioral; Biomedical Engineering; Brain; Carbon; Cells; Chemicals; Chronic; Cicatrix; Corpus striatum structure; Data; Development; Devices; Diagnostic; Dopamine; Electrical Engineering; Electrochemistry; Electrodes; Electronics; Electrophysiology (science); Elements; Fluorescent Dyes; Generations; Geometry; Goals; Health; Histologic; Human; Immune response; Immunohistochemistry; Implant; In Situ; Individual; Investigation; Joints; Learning; Mammals; Measures; Mental disorders; Methods; Modality; Modeling; Monitor; Motivation; Motor Cortex; Neuromodulator; Neurons; Neurosciences; Opioid Receptor; Periodicity; Play; Preparation; Psychological reinforcement; Rattus; Reaction; Research; Resolution; Rewards; Role; Sampling; Scanning; Series; Signal Transduction; Silicon; Site; Slice; Structure; Techniques; Testing; Time; Update; Work; brain tissue; carbon fiber; cell assembly; density; experimental study; implantation; information processing; innovation; multimodality; nanofabrication; nervous system disorder; neural circuit; neural prosthesis; neurochemistry; neurophysiology; novel; pre-clinical; prevent; public health relevance; relating to nervous system; skills; striosome; theories; time use; tool

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.

描述（由应用程序提供）：神经科学的主要目标是了解当地脑电路执行的计算。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电路中大多数神经元的尖峰活动。一个关键的原因是，标准电子太大，并造成对脑组织的损害太大。如果放置足够高的密度来采样大多数神经元，它们将破坏其打算监测的电路。理解局部大脑计算的另一个重要障碍是，电路动力学会因化学神经调节剂而迅速而动态地改变，而化学神经调节剂通常不会被观察到。可以使用快速扫描的循环伏安法实现对临界调节剂（例如多巴胺）的实时监测，但是该方法尚未与大规模电路记录有效合并。提出的工作将使用8µm碳螺纹电极的超密集阵列来克服这些障碍。这些足够僵硬，可以深入大脑，但足够小，可以避免破坏性的免疫响应。通过在电子之间使用80µm的距离，皮质层中的绝大多数神经元将在记录范围内。此外，碳螺纹电极非常适合使用伏安法化学敏感性。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高级新工具，最终在1024频道中，在自行到的大鼠中结合了电生理和电化学记录。 AIM 1涉及允许组装超密集阵列的硅框架的开发和测试，以及更新的头段，可以简单地监视数百个频道。 AIM 2将利用组织学过程中碳螺纹电极在原位切片的能力。这极大地支持了在微电路体系结构中定位单个记录站点并识别单个记录的神经元的能力。 AIM 3涉及对化学敏感性的碳螺纹电极的进一步优化，以及简单地跨许多电子的联合单单元记录和快速扫描的循环伏安法。总体而言，该项目结合了电动工程，神经生理学和神经化学的专业知识，以创建创新，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的工作方式产生变革性的影响。