Miniature, integrated and mass-producible fluorescence microscopes for in vivo brain imaging in freely behaving rodents

用于自由行为的啮齿动物体内脑成像的微型、集成和大规模生产的荧光显微镜

• 批准号: 9255696
• 负责人: Kunal Ghosh
• 金额: $ 72.62万
• 依托单位: INSCOPIX, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-24 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9255696
• 关键词: 3-Dimensional; Address; Adult; Algorithms; Alzheimer' s Disease; Animals; Attention Deficit Disorder; Autistic Disorder; Awareness; BRAIN initiative; Behavior; Behavioral; Boxing; Brain; Brain Diseases; Brain imaging; Brain region; Calcium; Cells; Chemicals; Communities; Complex; Computer software; Cone; Custom; Data; Data Analyses; Data Collection; Devices; Disease; Disease Progression; Electroencephalography; Electronics; Endoscopes; Evolution; Feedback; Future; Generations; Genetic; Goals; Grant; Graph; Head; Health; Heart; Human; Image; Imagery; Journals; Learning; Link; Longitudinal Studies; Marketing; Mechanics; Mental Depression; Mental disorders; Microscope; Motion; Mus; National Institute of Mental Health; Nature; Neurons; Neurosciences; Optics; Pattern; Performance; Phase; Physiological; Population; Process; Publications; Pythons; Rattus; Research Infrastructure; Resolution; Rodent; Rodent Model; Schizophrenia; Signal Transduction; Small Business Innovation Research Grant; Speed; Staging; Stream; System; Technology; Testing; Therapeutic; Therapeutic Intervention; Thinking; Time; Translations; Universities; Vision; Wireless Technology; Work; awake; base; behavior test; brain cell; commercialization; data acquisition; data exchange; data visualization; design; fluorescence microscope; imaging system; improved; in vivo; insight; lot production; mental function; neural circuit; neuropsychiatric disorder; next generation; prototype; relating to nervous system; technology development; tool; user-friendly

Project Summary There is increasing awareness that aberrant neural circuit activity is a core manifestation of many neuropsychiatric diseases, including autism, schizophrenia, depression and Alzheimer's disease. This realization has opened tantalizing prospects for more powerful and precise therapeutic approaches based on retuning of abnormal circuit activity. However, we still lack crucial understanding of neural activity patterns during normal behavior and how these patterns are altered in disease. Many rodent models of human brain diseases are now available, but neuroscientists are still hindered by lack of a technology for visualizing activity in large populations of genetically identified neurons in the brains of behaving animal subjects. Inscopix, Inc. spun out of Stanford University to commercialize a miniature fluorescence microscope technology that lets neuroscientists visualize Ca2+ dynamics in up to 1200 neurons simultaneously in awake, behaving rodents at cellular resolution. The microscope is easily carried on the head of a mouse or rat, and enables continuous recording from the same group of neurons in a single animal for periods of days to weeks. Used in conjunction with genetically encoded Ca2+ indicators and our custom-designed optical microendoscope probes, the microscope enables targeting of predefined neuronal subpopulations, and entry to brain regions inaccessible to other large-scale recording technologies. In Phase I, we developed and validated a new version of the microscope that is substantially higher performing and more robust than the original Stanford prototype. Around it we built the nVista imaging system: an end-to-end solution for in vivo brain imaging that includes the miniature microscope with an integrated HD camera and electronics, and user-friendly data acquisition hardware and software. The nVista system has now been disseminated for beta testing to over 100 labs around the globe. This Phase II project will move the nVista system forward in its next steps towards marketing to the general neuroscience community, through the following aims. (1) Create a next-generation version of the nVista system for commercial dissemination. Making use of feedback from early adopters, we will refine the system's design for greater performance, reliability and ease of use, by incorporating an electronic focusing mechanism, enabling higher speed data acquisition and seamless interfacing with other data collection systems; (2) Extend the technology to rats by developing an accessory array for the nVista microscope that includes a new base plate attachment mechanism, protective head-mounted cone and cable sheathing, optical probes, and an optical data link to support commutators; and (3) Develop a next-generation data analysis platform with faster processing, customizability, and better visualization tools.

项目概要 人们越来越认识到异常的神经回路活动是许多疾病的核心表现 神经精神疾病，包括自闭症、精神分裂症、抑郁症和阿尔茨海默病。这 实现为更强大、更精确的治疗方法开辟了诱人的前景 重新调整异常电路活动。然而，我们仍然缺乏对神经活动模式的关键理解 正常行为期间以及这些模式在疾病中如何改变。许多啮齿类动物的人脑模型 现在疾病已经存在，但神经科学家仍然因缺乏可视化活动的技术而受到阻碍 在行为动物受试者大脑中大量经过基因鉴定的神经元中。因斯科皮克斯公司 从斯坦福大学分离出来，将微型荧光显微镜技术商业化，让 神经科学家在清醒、行为正常的啮齿类动物中同时可视化多达 1200 个神经元的 Ca2+ 动态 细胞分辨率。该显微镜可轻松携带在小鼠或大鼠的头上，并可连续进行 对单个动物的同一组神经元进行数天至数周的记录。配合使用 借助基因编码的 Ca2+ 指示器和我们定制设计的光学显微内窥镜探头， 显微镜能够瞄准预先定义的神经元亚群，并进入大脑无法到达的区域 其他大规模记录技术。在第一阶段，我们开发并验证了新版本 与最初的斯坦福原型相比，该显微镜的性能更高，更坚固。 围绕它，我们构建了 nVista 成像系统：一种用于体内脑成像的端到端解决方案，包括 带有集成高清摄像头和电子器件以及用户友好的数据采集功能的微型显微镜 硬件和软件。 nVista 系统现已分发至 100 多个实验室进行 Beta 测试 地球仪。该第二阶段项目将推动 nVista 系统向市场营销迈进。 一般神经科学界，通过以下目标。 (1) 创建下一代版本 用于商业传播的 nVista 系统。利用早期采用者的反馈，我们将完善 系统的设计通过结合电子聚焦来实现更高的性能、可靠性和易用性 机制，实现更高速的数据采集并与其他数据采集无缝连接 系统； (2) 通过开发 nVista 显微镜的附件阵列将该技术扩展到大鼠， 包括新的底板连接机构、头部安装锥体和电缆护套、光学 探头和支持换向器的光学数据链路； (3) 开发下一代数据分析 具有更快处理速度、可定制性和更好可视化工具的平台。