BRAIN EAGER: Harnessing Light Sheet and Light Field Microscopy to Visualize Dynamic Adaptations to Neural Activity

BRAIN EAGER:利用光片和光场显微镜可视化神经活动的动态适应

基本信息

  • 批准号:
    1650406
  • 负责人:
  • 金额:
    $ 30万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-15 至 2018-08-31
  • 项目状态:
    已结题

项目摘要

This BRAIN EAGER will support an interdisciplinary team of investigators to jointly develop and deploy optimized light sheet microscopy and novel genetically encoded probes to image synaptic function in the intact nervous system. This team will optimize a novel 3D imaging microscope, in which multi-photon light sheet illumination is combined with light field microscopy to permit a single snapshot to capture the full 3D image, enabling the team to visualize these probes with unprecedented speed and coverage. They will also develop new genetically encoded glutamate and calcium probes, targeted to defined synaptic compartments, to optimize signal magnitude and report synaptic activity with high sensitivity and fidelity. These innovations will be exploited to synergistically visualize synaptic structure and monitor glutamate and calcium dynamics in the intact Drosophila central nervous system. Although these tools could be used in a variety of settings in the vertebrate or the invertebrate nervous system, these will be first applied to address the fundamental relationship between sleep and synaptic plasticity. Although sleep is ancient, the essential biological function of this behavior remains a great mystery of science. This project will explore the exciting possibility that a fundamental function of sleep, operating at the level of individual neurons and synapses, is the homeostatic modulation of synaptic strength. Addressing this hypothesis has been beyond our capabilities because visualizing neural activity in the central nervous system during sleep-wake behavior has been limited in both speed and resolution. Through a combination of new genetically encoded probes reporting synaptic structure and activity and cutting-edge imaging approaches, this project will permit the imaging of synapses over time without perturbing the nervous system or the sleep-wake cycle. These test experiments will advance our knowledge of the complex, fundamental, and poorly understood signaling systems that orchestrate the homeostatic control of synaptic strength, and their modulation during sleep behavior. The education and outreach activities of the research team will be intimately linked with their research programs, and will include a research project with local inner-city Los Angeles high school students investigating sleep and circadian behavior. In addition, a new undergraduate course will be developed exploring the biological functions of sleep.
这个BRAIN EAGER将支持一个跨学科的研究团队,共同开发和部署优化的光片显微镜和新型遗传编码探针,以成像完整神经系统中的突触功能。该团队将优化一种新型的3D成像显微镜,其中多光子光片照明与光场显微镜相结合,以允许单个快照捕获完整的3D图像,使团队能够以前所未有的速度和覆盖范围可视化这些探针。他们还将开发新的遗传编码的谷氨酸和钙探针,靶向定义的突触区室,以优化信号幅度并以高灵敏度和保真度报告突触活动。这些创新将被利用来协同可视化突触结构,并监测完整的果蝇中枢神经系统中的谷氨酸和钙动力学。 虽然这些工具可以用于脊椎动物或无脊椎动物神经系统的各种设置,但这些工具将首先应用于解决睡眠和突触可塑性之间的基本关系。虽然睡眠是古老的,但这种行为的基本生物功能仍然是科学的一个巨大谜团。这个项目将探索令人兴奋的可能性,即睡眠的基本功能,在单个神经元和突触的水平上运作,是突触强度的稳态调节。解决这个假设已经超出了我们的能力,因为在睡眠-觉醒行为期间可视化中枢神经系统中的神经活动在速度和分辨率方面都受到限制。通过将报告突触结构和活动的新基因编码探针与尖端成像方法相结合,该项目将允许在不干扰神经系统或睡眠-觉醒周期的情况下对突触进行成像。这些测试实验将推进我们对复杂的,基本的和知之甚少的信号系统的知识,这些信号系统协调突触强度的稳态控制,以及它们在睡眠行为中的调节。研究小组的教育和推广活动将与他们的研究计划密切相关,并将包括一个与当地洛杉矶市中心高中学生一起调查睡眠和昼夜节律行为的研究项目。此外,还将开发一门新的本科课程,探索睡眠的生物学功能。

项目成果

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Dion Dickman其他文献

Building and modifying diverse synaptic properties: Insights from Drosophila
构建和改变多样的突触特性:来自果蝇的启示
  • DOI:
    10.1016/j.conb.2025.102995
  • 发表时间:
    2025-06-01
  • 期刊:
  • 影响因子:
    5.200
  • 作者:
    Kaikai He;Dion Dickman
  • 通讯作者:
    Dion Dickman

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