Optimization, Application, and Dissemination of Imaging Modules for High-speed Mesoscopic Volumetric Recording of Neuroactivity in Scattering Brains

散射脑神经活动高速介观体积记录成像模块的优化、应用和传播

• 批准号: 10657354
• 负责人: Alipasha Vaziri
• 金额: $ 140.36万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657354
• 关键词: Address; Animals; Behavioral; Biological; Brain; Brain region; Calcium; Cells; Code; Cognitive; Collaborations; Complex; Coupled; Development; Feedback; Fluorescence; Fluorescence Microscopy; Freedom; Image; Imaging Device; Imaging technology; Industrialization; Laboratories; Letters; Light; Maps; Microscopy; Modeling; Mus; Neurons; Optics; Performance; Physiological; Population; Reporter; Resolution; Resource Sharing; Resources; Rodent; Scanning; Scheme; Speed; Synapses; System; Technology; Testing; Tissues; Visual Cortex; awake; calcium indicator; design; design,build,test; flexibility; imaging approach; improved; insight; meter; neuroimaging; neuronal circuitry; neurotechnology; open source; optical imaging; parallel computer; prototype; real world application; sensory input; spatiotemporal; tool development; two-photon; user-friendly

Project Summary / Abstract A number of recent observations suggest that complex brain functions in the mammalian brain emerge from highly parallel computation in which information about sensory inputs, internal states, and behavioral parameters are mapped onto highly distributed brain-wide neuronal populations. This calls for neurotechnologies that allow for large-scale recording of neuro-activity across tissue depths and brain regions at physiological timescales and cellular resolution in awake and behaving animals. While recent advancements in optical tool development based on the combination of two-photon scanning fluorescence microscopy (2p M) and genetically-encoded calcium indicators (GECIs) as reporters of neuro-activity have been aimed at addressing these needs by developing faster, larger-scale, and volumetric calcium (Ca2+) imaging technologies, a fundamental unsolved challenge in this context is navigating the inherent tradeoffs between speed, resolution, and the size of the recording volume in a principled and scalable manner. Our lab has recently established criteria for such optimal recording schemes which has led to the realization of a new high-speed volumetric Ca2+ imaging approach termed Light Beads Microscopy (LBM). Through LBM, we have demonstrated fluorescence lifetime limited volumetric recording of neuro-activity at a single-cell resolution of up to 1 million neurons within both cortical hemispheres of awake, behaving mice. In this project, we will pursue a multipronged strategy towards the optimization, biological applications, and effective dissemination of our LBM technology while extending its performance. This will result in a more robust, less complex, and more user-friendly version of our LBM technology. To enable its broad and effective dissemination, in the second part of the project, we will utilize feedback from our α-testers to design, build, and disseminate β-prototypes of our system that will be distributed to several end-user laboratories who will be testing and applying our LBM technology in the context of their biological questions. This β-prototype will also form the basis for commercial dissemination of our technology as well as a parallel effort for its open-source dissemination.

项目概要/摘要 最近的一些观察表明，哺乳动物大脑中的复杂大脑功能是由高度并行计算产生的，其中有关感觉输入、内部状态和行为参数的信息被映射到高度分布的全脑神经群体上，这需要允许的神经技术。在清醒和行为动物的生理时间尺度和细胞分辨率下大规模记录组织深度和大脑区域的神经活动，而基于双光子扫描荧光显微镜（2p M）和光学工具开发的最新进展。作为神经活动产生者的盟友编码钙指示剂 (GECI) 旨在通过开发更快、更大规模和体积钙 (Ca2+) 成像技术来满足这些需求，在这种遗传背景下，一个未解决的基本挑战是驾驭固有的我们的实验室最近以原则性和可扩展的方式在速度、分辨率和记录体积大小之间进行权衡，从而实现了一种新的高速体积 Ca2+ 成像方法。光珠显微镜 (LBM)。通过 LBM，我们展示了对清醒、行为小鼠的两个皮质半球内高达 100 万个神经元的神经活动的荧光寿命有限体积记录。采取多管齐下的策略来优化、生物应用和有效传播我们的 LBM 技术，同时扩展其性能，这将导致我们的 LBM 技术变得更强大、更简单、更用户友好。广泛而有效的传播，在该项目的第二部分，我们将利用 α 测试人员的反馈来设计、构建和传播我们系统的 β 原型，该原型将分发给几个最终用户实验室，他们将进行测试和将我们的 LBM 技术应用于其生物学问题，该 β 原型也将构成我们技术的商业传播以及其开源传播的并行努力的基础。