Multi-color optical voltage imaging of neural activity in behaving animals

行为动物神经活动的多色光学电压成像

基本信息

批准号：
10415945
负责人：
MARK J SCHNITZER
金额：
$ 88.99万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-15 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10415945
关键词：
Action Potentials Address Amino Acid Sequence Animal Behavior Animals Area BRAIN initiative Brain Brain imaging Categories Cells Cephalic Chronic Color Complement Computer software Data Deposition Devices Disease Dorsal Educational workshop Electrodes Engineering Feedback Fiber Optics Fluorescence Resonance Energy Transfer Genetic Head Health Image Imaging Device Imaging Techniques Individual Intelligence Kinetics Knowledge Label Laboratories Learning Licensing Light Machine Learning Mammals Membrane Membrane Potentials Methods Microscope Molecular Monitor Mus Neocortex Neurons Opsin Optical Instrument Optics Outcome Pattern Performance Population Preparation Proteins Publishing R24 Research Resolution Resource Sharing Rodent Science Scientist Shapes Slice Specificity Speed Surface Techniques Testing Time Training Transgenic Organisms United States National Institutes of Health Universities Validation Variant Viral Vector Visit Work absorption awake brain shape cell type design fly genetic signature high throughput screening imaging facilities imaging modality imaging study improved information processing innovation instrument invention machine learning framework machine learning method microendoscopy millisecond mutant neocortical neural neural circuit neuroimaging neurophysiology new technology novel novel strategies optical fiber optogenetics public repository response screening sensor success synergism tool voltage

Action Potentials Address Amino Acid Sequence Animal Behavior Animals Area BRAIN initiative Brain Brain imaging Categories Cells Cephalic Chronic Color Complement Computer software Data Deposition Devices Disease Dorsal Educational workshop Electrodes Engineering Feedback Fiber Optics Fluorescence Resonance Energy Transfer Genetic Head Health Image Imaging Device Imaging Techniques Individual Intelligence Kinetics Knowledge Label Laboratories Learning Licensing Light Machine Learning Mammals Membrane Membrane Potentials Methods Microscope Molecular Monitor Mus Neocortex Neurons Opsin Optical Instrument Optics Outcome Pattern Performance Population Preparation Proteins Publishing R24 Research Resolution Resource Sharing Rodent Science Scientist Shapes Slice Specificity Speed Surface Techniques Testing Time Training Transgenic Organisms United States National Institutes of Health Universities Validation Variant Viral Vector Visit Work absorption awake brain shape cell type design fly genetic signature high throughput screening imaging facilities imaging modality imaging study improved information processing innovation instrument invention machine learning framework machine learning method microendoscopy millisecond mutant neocortical neural neural circuit neuroimaging neurophysiology new technology novel novel strategies optical fiber optogenetics public repository response screening sensor success synergism tool voltage

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项目摘要

Abstract Groundbreaking work within the NIH BRAIN Initiative has revealed many new types of neurons and their genetic signatures. The dividends from this research will include sophisticated tools allowing selective genetic access to these cell-types, such as for imaging, optogenetic or tracing studies. To complement these powerful genetic tools, it will be equally important to have new imaging techniques that can reveal how multiple neuron- types work together in the live brain to support information-processing and construct different brain states. To address this challenge, Stanford University and The John B. Pierce Laboratory at Yale University will create optical techniques for imaging the concurrent voltage dynamics of up to 4 separate neuron-types in behaving animals. First, we will combine machine learning methods and an automated, high-throughput protein screening platform to engineer 4 different categories of genetically encoded fluorescent optical indicators of neuronal transmembrane voltage. We will then innovate several types of optical instruments tailored to work in conjunction with the new voltage indicators. These instruments will enable unprecedented studies of voltage rhythms and spiking dynamics in 2–4 genetically identified neuron-types in superficial and deep brain areas of awake behaving animals. One instrument will allow us to track the concurrent, population voltage oscillations of 2 neuron-types in freely behaving rodents. Another instrument, an optical mesoscope, will enable imaging studies of voltage waves and oscillations across the entire neocortical surface of behaving mice. A third device will be a high-speed miniature microscope for tracking neural dynamics at single cell-, single spike-resolution in freely behaving mice. Lastly, we will develop the capability to image with millisecond-scale precision the simultaneous spiking dynamics of 4 targeted neuron-types in either cortical or deep brain areas. Five external beta-tester labs will evaluate all these innovations in live mice and flies and provide critical user-feedback. If our work succeeds, it will be a ‘game-changer’ for studies of brain dynamics, yielding vital knowledge about how different neuron-types synergize their dynamics to shape animal behavior and the brain’s global states in health and disease. To facilitate this outcome, we plan a 5-fold strategy for resource sharing: (i) All voltage-indicator constructs, viral vectors, transgenic flies, software and screening data will be deposited at public repositories for open distribution; (ii) All instrument designs will be published in extensive detail to facilitate replication; (iii) Our novel imaging devices will be integrated into an existing NIH-supported, publicly accessible facility for brain-imaging in rodents; (iv) In project years 2–4, we will conduct 4 training workshops for 40 visiting scientists per year (120 in total) to learn the new technologies firsthand. These visitors will also provide extensive user-feedback; (v) We will license our imaging instruments for commercial distribution. Overall, we expect our project will lead to major conceptual advances in brain science and multiple new technologies that will reshape the practice of mammalian brain imaging.

抽象的 NIH脑倡议中的突破性工作揭示了许多新型的神经元及其遗传特征。这项研究的股息将包括复杂的工具，允许选择性遗传访问这些细胞类型，例如成像，光遗传学或追踪研究。完成这些强大的遗传工具，拥有新的成像技术同样重要，这些技术可以揭示多个神经元如何类型在活大脑中一起工作，以支持信息处理并构建不同的大脑状态。为了应对这一挑战，斯坦福大学和耶鲁大学的约翰·皮尔斯实验室将创建光学技术，用于成像多达4种独立神经元类型的并发电压动力学行为动物。首先，我们将结合机器学习方法和一种自动化的高通量蛋白筛选平台工程师4种不同类别的基因编码荧光光学指标神经元跨膜电压。然后，我们将创新几种用于工作的光学仪器与新电压指示器的连接。这些仪器将实现前所未有的电压研究在2-4个遗传鉴定的浅表和深脑区域的神经类型中的节奏和尖峰动力学醒来的动物。一种仪器将使我们能够跟踪并发的人口电压振荡自由行为啮齿动物中的2种神经元类型。另一个乐器是光学介质，将启用成像对行为小鼠整个新皮质表面的电压波和振荡的研究。第三个设备将是一个高速微型显微镜自由表现的老鼠。最后，我们将发展能够以毫秒级的精度图像形象皮质或深脑区域中4种靶向神经类型的4种靶向神经类型的同时尖峰动力学。五个外部 Beta-Tester Labs将评估活鼠和苍蝇中的所有这些创新，并提供关键的用户反馈。如果我们的工作成功，那将是对大脑动态研究的“改变游戏规则”，产生重要的知识关于不同的神经类型如何协同动力来塑造动物行为和大脑的全球健康和疾病的国家。为了促进这一结果，我们计划了一项5倍资源共享的策略：（i）电压指示构建体，病毒载体，转基因苍蝇，软件和筛选数据将存放在公共存储库以进行开放分发；（ii）所有仪器设计将以广泛的详细信息发布到促进复制；（iii）我们的新型成像设备将集成到现有的NIH公开中啮齿动物的大脑成像的无障碍设施；（iv）在项目2 - 4年中，我们将举办4个培训研讨会每年有40位来访的科学家（总共120位）亲身学习新技术。这些访客也将提供广泛的用户反馈；（v）我们将许可我们的成像工具的商业分销。总体而言，我们预计我们的项目将导致脑科学和多个新的概念进步可以重塑哺乳动物脑成像实践的技术。