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）：脑切片制备提供了惊人的细胞和回路水平脑功能的细节。 有许多类的问题，只能解决使用脑切片，但控制空间和时间的神经化学微环境在实验中是困难的使用标准浴交换层流切片室。 在我们的工作中，我们正在探索多巴胺（DA）和其他神经调节剂可能会影响前额叶皮层微电路的能力，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信号传导被认为是通过未知的机制受损，或者在帕金森病中，从腹侧被盖区（VTA）到皮质的DA神经支配丢失。 我们希望能够在精确的时间和空间控制下将神经化学物质（如DA）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，我们仅限于在整个切片上更换浸浴介质或使用移液管将化合物喷到切片上或切片中，这阻碍了电生理和成像通路并且没有得到很好的控制。 一个更精确和通用的方法将是无价的，对我们和许多其他人做脑切片生理学。 我们已经创建了原型微流体脑切片装置（5 BSD），其将现成的脑切片腔室与设置在腔室的底表面中的微流体通道阵列结合（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，复制和与其他研究人员共享设备是微不足道的。 此外，我们的5 BSD可无缝集成到标准生理学/成像室中，可立即供整个切片生理学社区使用。 有了这项技术，我们可以利用我们选择的时间剖面，将神经化学物质和任何其他可溶性因子的流动定位到大脑切片中的精确位置。 我们对DA特别感兴趣，我们可以使用循环伏安法（CV）定量组织中的DA递送。 因此，我们将使用DA交付给我们的2个具体目标的小鼠皮层-一个是进一步完善和发展的技术和其他测试DA对皮层活动patterns.Public健康相关性的影响：我们的方法将提供一种新颖的，复杂的方法来测试调节性神经递质及其拮抗剂对疾病的电路动力学的影响，如精神分裂症和帕金森氏病。 很难想象有一种更好的方法来理解皮层微电路是如何工作的，而不是直接成像其功能，同时控制神经化学微环境。 我们设想，我们的工作将导致一整套设备，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，我们努力整合到目前使用的腔室技术中，这将为生理学家轻松立即使用的其他此类工作设定标准

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