microBSD:Spatiotemporal control of neurochemical tone in the brain slice using mi

microBSD：使用 mi 对脑切片中的神经化学音调进行时空控制

基本信息

批准号：
7835750
负责人：
David Eddington
金额：
$ 19.63万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-07 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7835750
关键词：
3-Dimensional Address Amaze Area Bathing Brain Characteristics Cognitive Communities Corpus striatum structure Custom Detection Development Devices Dimensions Disease Dopamine Dyes Electrophysiology (science)Engineering Equipment Fluorescence Fluorescence Microscopy Functional disorder Image Interneurons Lead Libraries Location Measures Methods Microfluidic Microchips Microfluidics Microscopy Mus Neuromodulator Neurons Neurotransmitters Parkinson Disease Pattern Physiology Preparation Property Pump Research Research Personnel Schizophrenia Short-Term Memory Signal Transduction Slice Surface Technology Testing Thalamic structure Time Tissues Ventral Tegmental Area Work cognitive function design executive function flexibility fluorescence imaging indexing interest nerve supply neurochemistry novel prototype receptor research study response spatiotemporal

项目摘要

DESCRIPTION (provided by applicant): The brain slice preparation has provided amazing access to details of cellular and circuit level brain function. There are many classes of questions that can only be addressed using the brain slice, but controlling the spatial and temporal neurochemical microenvironment during experiments is difficult using standard bath exchange laminar flow slice chambers. In our work we are exploring how dopamine (DA) and other neuromodulators might influence the ability of the prefrontal cortical microcircuit to maintain spatiotemporal activity patterns associated with working memory, cognitive flexibility and other executive functions. Years of research have demonstrated the relevance of dysfunction of DA to cognitive function - for example in Schizophrenia where DA signaling is thought to be impaired through unknown mechanisms or in Parkinson's disease where DA innervation to cortex from the ventral tegmental area (VTA) is lost. We would like to be able to apply neurochemicals such as DA to different areas of the same slice under precise temporal and spatial control in order to explore effects on network activity in a way that is relevant to the intact brain. Currently, we are limited to exchanging the bathing medium over the whole slice or puffing compounds onto or into the slice using pipettes, which impede electrophysiological and imaging access and are not well controlled. A more precise and versatile method would be invaluable for us and for many others doing brain slice physiology. We have created a prototype microfluidic brain slice device (5BSD) that marries an off-the shelf brain slice chamber with an array of microfluidic channels set into the bottom surface of the chamber (http://www.jove.com/index/Details.stp?ID=302). This device is created using rapid prototyping and, once optimized, it is trivial to replicate and share the devices with other investigators. Additionally, our 5BSD integrates seamlessly into standard physiology/imaging chambers, it is immediately available to the whole slice physiology community. With this technology we can address the flow of neurochemicals and any other soluble factors to precise locations in the brain slice with the temporal profile we choose. We are interested specifically in DA and we can quantify DA delivery in tissue using cyclic voltammetry (CV). Therefore we will use DA delivery to mouse cortex for our 2 specific aims - one to refine and develop the technology further and the other to test the effects of DA on cortical activity patterns.PUBLIC HEALTH RELEVANCE: Our approach will offer a novel, sophisticated approach to test the effects of modulatory neurotransmitter and their antagonists on the circuit dynamics in diseases as diverse as schizophrenia and Parkinson's disease. It is difficult to imagine a better way of understanding how the cortical microcircuit works than by directly imaging its function while controlling the neurochemcial microenvironment. We envision that our work here will lead to a whole class of devices that will allow researchers to control the microenvironment of the brain slice preparation to address a variety of questions and that our efforts to integrate into currently used chamber technology will set a standard for other such efforts to be easily and immediately available for physiologists

描述（由申请人提供）：脑切片制备提供了对细胞和电路水平脑功能细节的惊人了解。有许多类问题只能使用脑切片来解决，但使用标准水浴交换层流切片室很难控制实验过程中的空间和时间神经化学微环境。在我们的工作中，我们正在探索多巴胺（DA）和其他神经调节剂如何影响前额皮质微电路维持与工作记忆、认知灵活性和其他执行功能相关的时空活动模式的能力。多年的研究已经证明了 DA 功能障碍与认知功能的相关性，例如在精神分裂症中，DA 信号被认为通过未知机制受损；或者在帕金森病中，DA 从腹侧被盖区 (VTA) 到皮质的神经支配丧失。我们希望能够在精确的时间和空间控制下将 DA 等神经化学物质应用于同一切片的不同区域，以便以与完整大脑相关的方式探索对网络活动的影响。目前，我们仅限于更换整个切片上的沐浴介质或使用移液器将化合物吹入切片上或切片内，这阻碍了电生理和成像的访问并且不能很好地控制。一种更精确、更通用的方法对于我们和许多其他从事脑切片生理学研究的人来说将是无价的。我们创建了一个原型微流体脑切片装置 (5BSD)，它将现成的脑切片室与设置在室底部表面的微流体通道阵列结合在一起 (http://www.jove.com/index/Details .stp?ID=302）。该设备是使用快速原型设计创建的，一旦优化，复制并与其他研究人员共享该设备就变得很简单。此外，我们的 5BSD 无缝集成到标准生理学/成像室中，整个切片生理学社区可以立即使用。通过这项技术，我们可以根据我们选择的时间曲线来解决神经化学物质和任何其他可溶性因子流向大脑切片中精确位置的问题。我们对 DA 特别感兴趣，我们可以使用循环伏安法 (CV) 量化组织中的 DA 传递。因此，我们将使用 DA 递送至小鼠皮质来实现 2 个具体目标 - 一是进一步完善和开发技术，二是测试 DA 对皮质活动模式的影响。公共健康相关性：我们的方法将提供一种新颖、复杂的方法测试调节性神经递质及其拮抗剂对精神分裂症和帕金森病等多种疾病的回路动力学的影响。很难想象有比在控制神经化学微环境的同时直接对其功能进行成像更好的方式来理解皮质微电路的工作原理。我们设想，我们在这里的工作将带来一整类设备，使研究人员能够控制脑切片制备的微环境，以解决各种问题，并且我们努力整合到当前使用的室技术中，将为其他设备设定标准。生理学家可以轻松、立即地利用这些努力