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

• 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
• 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

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）：大脑切片制剂为细胞和电路水平脑功能的细节提供了惊人的访问。 只有大脑切片才能解决很多类别的问题，但是使用标准浴室层流层流室在实验过程中控制空间和时间神经化学微环境很困难。 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叶皮质微电路的能力，以维持与工作记忆，认知灵活性和其他执行功能相关的时空活动模式。 多年的研究表明，DA功能障碍与认知功能的相关性 - 例如，在精神分裂症中，DA信号传导被认为是通过未知机制或帕金森氏病损害的DA信号，在该机制中，DA神经支配从腹侧段盖区域（VTA）损失了DA神经化。 我们希望能够在精确的时间和空间控制下将神经化学物（例如DA）应用于同一切片的不同区域，以探索与完整大脑相关的方式探索对网络活动的影响。 当前，我们仅限于使用移液器将浴室在整个切片或膨化化合物上交换到切片上或进入切片，这会阻碍电生理和成像访问，并且无法得到很好的控制。 对于我们和许多其他从事脑切片生理学的人来说，一种更精确和通用的方法将是无价的。 我们创建了一个原型的微流体脑切片设备（5BSD），该设备将架子式脑切片室与一系列的微流体通道（http://wwwww.ove.com/index/index/detex/detex/details.stp?id=302）相结合。 该设备是使用快速原型制作创建的，一旦优化，与其他研究人员进行复制和共享设备是微不足道的。 此外，我们的5BSD将无缝集成到标准生理/成像室中，它立即可供整个Slice生理学界使用。 通过这项技术，我们可以通过我们选择的时间概况来解决神经化学物质和任何其他可溶性因素的流动。 我们对DA特别感兴趣，并且可以使用环状伏安法（CV）来量化组织中的DA递送。 因此，我们将对我们的两个特定目的使用DA传递到小鼠皮层 - 一个是进一步完善和开发技术，另一个是测试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的，精致的方法来测试调节性神经释放剂及其动力学对疾病的动力学对疾病的动力学的影响。 很难想象一种更好的方法来理解皮质微电路的工作原理，而不是通过在控制神经化学微环境的同时直接对其功能进行成像。 我们设想，我们的工作将导致整个设备，这些设备将使研究人员能够控制大脑切片准备的微环境，以解决各种问题，并且我们将当前使用的室内技术融入到当前使用的室内技术中的努力将为其他这样的努力设定标准，以轻松并立即为生理学家提供。

项目成果

Precise spatial and temporal control of oxygen within in vitro brain slices via microfluidic gas channels.

• DOI: 10.1371/journal.pone.0043309
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Mauleon G;Fall CP;Eddington DT
• 通讯作者: Eddington DT

Enhanced loading of Fura-2/AM calcium indicator dye in adult rodent brain slices via a microfluidic oxygenator.

通过微流体充氧器增强成年啮齿动物脑切片中 Fura-2/AM 钙指示剂染料的负载。

• DOI: 10.1016/j.jneumeth.2013.04.007
• 发表时间: 2013
• 期刊: Journal of neuroscience methods
• 影响因子: 3
• 作者: Mauleon,Gerardo;Lo,JoeF;Peterson,BethanyL;Fall,ChristopherP;Eddington,DavidT
• 通讯作者: Eddington,DavidT