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（由申请人提供）：神经科学的一个主要目标是理解局部大脑回路执行的计算，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大多数神经元的尖峰活动。一个关键原因是标准电极太大，会对脑组织造成太大损伤，如果放置的密度足够高以对大多数神经元进行采样，它们会破坏它们要监测的电路。了解当地的障碍大脑计算的一个特点是，化学神经调节剂会迅速而显着地改变电路动力学，而化学神经调节剂通常无法观察到，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，但该方法尚未与化学神经调节剂有效结合。拟议的工作将在克服这些障碍方面取得重要进展，使用超密集的 8μm 碳线电极阵列，这些电极的硬度足以插入大脑深处，但又足够小。通过使用电极之间的 80μm 距离，皮层内的绝大多数神经元将在记录范围内，此外，碳线电极非常适合使用伏安法进行化学传感。通过一系列模块化步骤进行神经科学研究的新工具，最终在自由行为的大鼠中实现 1024 通道、组合电生理学和电化学记录，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测数百个通道的更新探头将利用碳丝电极在组织学处理过程中进行原位切片的能力，这极大地促进了个体定位的能力。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。结合了电气工程、神经生理学和神经化学方面的专业知识，创造出创新、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变革性影响。