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（由适用提供）：神经科学的最大挑战之一是了解大脑过程，编码，存储和检索信息中的神经元电路如何。应对这一挑战将需要方法来记录自由行使动物中完整的神经元网络的活性。随着神经元活性和光遗传执行器的遗传编码指标的发展的壮观进展，现在呼吁在长时间的时间内在自由移动的小鼠中进行图像和操纵大量神经元的活性。需要多通道成像，以根据其独特的基因表达曲线或投影模式明确地识别单个神经元，并且需要灵活的平台，以便可以轻松地适应范围来解决潜水神经科学问题。需要光遗传学能力来在细胞活动模式和行为之间建立因果关系。最后，目前可用的技术受到限制，因为它要求小鼠通过电线束缚，从而限制其行为范围和与其他动物或环境互动的能力。此外，商业微型范围非常昂贵，无法更改以满足个人最终用户需求。在这里，我们试图通过开发真正的开源下一代两通道光遗传学，无线化，微型化学显微镜，用于成像和跟踪自由移动小鼠的大型神经细胞群体的成像和跟踪活动模式，以记住现有技术的短缺。我们将设计，制造，优化和测试：用于成像两种荧光团的两通道显微镜（AIM 1），一种具有光遗传学能力的显微镜，用于成像和光遗传学兴奋（AIM 2），无线微型化学显微镜（AIM 3）（AIM 3），以及具有组合的两种晶体，两种晶体，光源，无线材料和无线能力（AIM）的显微镜（AIM 3）。在整个过程中，我们将建立一个在线环境，以与神经科学社区共享显微镜，抬高其他人以构建，修改和植入显微镜，并使用我们的软件分析神经元活动数据。我们的新可穿戴显微镜将通过首次允许对数百个已鉴定的神经元和其他细胞的活性（例如自由行为的动物中的星形胶质细胞）进行成像和操纵，从而对神经科学产生变革性的影响。