Building and sharing next generation open-source, wireless, multichannel miniaturized microscopes for imaging activity in freely behaving mice

构建和共享下一代开源、无线、多通道微型显微镜，用于对自由行为的小鼠进行成像活动

• 批准号: 9302567
• 负责人: Peyman Golshani
• 金额: $ 87.97万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 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 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9302567
• 关键词: Address; Animals; Astrocytes; Behavior; Biological Models; Biological Neural Networks; Birds; Brain; Calcium; Calcium Signaling; Cells; Chiroptera; Code; Cognition; Communities; Computer software; Data; Development; Devices; Environment; Feedback; Gene Expression; Generations; Goals; Hippocampus (Brain); Image; Implant; Individual; Information Retrieval; Instruction; Interneurons; Laboratories; Letters; Lifting; Mechanics; Memory; Methods; Microscope; Molecular; Molecular Profiling; Mus; Neurons; Neurosciences; Operative Surgical Procedures; Pattern; Performance; Play; Population; Primates; Process; Research; Research Personnel; Rodent; Role; System; Technology; Testing; Time; Wireless Technology; awake; base; calcium indicator; cell type; cost; design; experience; flexibility; fluorophore; implantation; meetings; microscopic imaging; miniaturize; movie; neural circuit; next generation; open source; optogenetics; public health relevance; relating to nervous system; tool; web site

 DESCRIPTION (provided by applicant): One of the biggest challenges in neuroscience is to understand how neural circuits in the brain process, encode, store, and retrieve information. Meeting this challenge will require methods to record the activity of intact neural networks in freely behaving animals. Spectacular advances with the development of genetically encoded indicators of neural activity and optogenetic actuators now call for methods to image and manipulate the activity of large populations of identified neurons in freely moving mice over prolonged periods of time. Multi-channel imaging is needed to unequivocally identify individual neurons based on their unique gene expression profiles or projection patterns, and a flexible platform is needed so that the scopes can be easily adapted to address diverse neuroscience questions. Optogenetic capability is needed to draw causal connections between cellular activity patterns and behavior. Finally, currently available technology is limited because it requires the mice to be tethered by wires, limiting their range of behaviors and ability to interact with other animals or their environment. In addition, commercial miniaturized scopes are extremely expensive, and cannot be altered to meet individual end-user needs. Here, we seek to remedy shortfalls in existing technology by developing truly open source next-generation two-channel optogenetics-capable, wireless, miniaturized microscopes for imaging and tracking activity patterns of large neural-cell populations in freely moving mice. We will design, manufacture, optimize and test: a two-channel microscope for imaging two fluorophores (Aim 1), an optogenetics-capable microscope for imaging and optogenetic excitation (Aim 2), a wireless miniaturized microscope (Aim 3), and a microscope with combined two-channel, optogenetics, and wireless capability (Aim 4). All throughout, we will build an online environment for sharing our microscopes with the neuroscience community, lifting barriers for others to build, modify, and implant the microscopes and analyze neural activity data with our software. Our new wearable microscopes will have a transformative impact on neuroscience by permitting for the first time the imaging and manipulation of the activity of hundreds of identified neurons and other cells such as astrocytes in freely behaving animals.

 描述（由申请人提供）：神经科学中最大的挑战之一是了解大脑中的神经回路如何处理、编码、存储和检索信息，迎接这一挑战将需要记录完整神经网络自由行为的活动。随着神经活动基因编码指标和光遗传学执行器的发展取得了巨大的进步，现在需要对自由移动的小鼠中大量已识别神经元的活动进行长时间成像和操纵的方法。根据其独特的基因表达谱或投影模式明确识别单个神经元，并且需要一个灵活的平台，以便可以轻松地调整范围来解决不同的神经科学问题，需要光遗传学能力来绘制细胞活动模式和行为之间的因果关系。最后，目前可用的技术是有限的，因为它需要用电线拴住小鼠，限制了它们的行为范围和与其他动物或其环境互动的能力。此外，商业微型瞄准镜非常昂贵，并且不能满足个体的需求。在这里，我们寻求通过真正开发开源下一代双通道光遗传学无线微型显微镜来弥补现有技术的缺陷，用于对自由移动的小鼠中的大型神经细胞群进行成像和跟踪活动模式。我们将设计、制造、优化和测试：用于对两种荧光团进行成像的双通道显微镜（目标 1）、用于成像和光遗传学激发的光遗传学显微镜（目标 2）、无线显微镜。小型化显微镜（目标 3），以及具有双通道、光遗传学和无线功能的显微镜（目标 4）。自始至终，我们将建立一个与神经科学界共享我们的显微镜的在线环境，为其他人消除构建障碍。 、修改和植入显微镜并使用我们的软件分析神经活动数据，我们的新型可穿戴显微镜将首次允许对数百个已识别神经元和其他细胞（例如，神经元）的活动进行成像和操作，从而对神经科学产生变革性影响。自由行为动物的星形胶质细胞。