Development of compressed ultrafast microscopy for real-time multi-scale neuroimaging

开发用于实时多尺度神经成像的压缩超快显微镜

• 批准号: RGPIN-2017-05959
• 负责人: Liang, Jinyang
• 金额: $ 2.99万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=710139
• 关键词: Development; compressed; ultrafast; microscopy; real

A prevalent goal in neuroscience is to record fast, spontaneous neural activities occurring at varied spatial and temporal scales in real time. Conventional electrophysiology relied on microelectrodes to record neuron's membrane potentials. However, in general, this invasive approach is limited in the number of recording sites, vulnerable to environmental electrical noises, and challenged for longitudinal monitoring. Optical recording, on the other hand, has emerged as an attractive approach to measuring neural activities with inherent advantages in non-invasiveness, recording parallelism, and spatiotemporal scalability. Optical voltage imaging encompasses two major constituents: voltage indicators and optical imaging instruments. Recent advances in biochemistry have enabled fast-response, high-sensitivity fluorescent voltage indicators. However, existing optical instruments still lack sufficient speed, scalability, and sensitivity. Thus, real-time, multi-scale optical imaging of neural activities has not been achieved. The overall objective of this Discovery program is to develop unique imaging techniques and devices for real-time, multi-scale optical neuroimaging. Our long-term goal is to map the functional connectome of the brain. For the next five years, we propose three projects to investigate optical voltage imaging from the technological development and neuroscience applications in a collaborative effort. Specifically, these projects aim (1) To develop compressed ultrafast microscope (CUMIC) for real-time, multi-scale optical voltage imaging (2) To investigate biophysical properties of the axon initial segment and the node of Ranvier under pathological conditions in vitro using CUMIC at 10 kHz2 MHz (3) To determine neural encoding and neuroplasticity to sensory stimulations in freely behaving animals using CUMIC at 110 kHz The results of the proposed program will represent a unique contribution in biophotonics by significantly enhancing our imaging capability of neurons from sub-cellular to organism levels. The state-of-the-art CUMIC system will greatly assist neuroscientists in understanding open questions in neuronal biophysics, circuit neuroscience, and behavioral outputs. CUMIC will also pave the way for real-time high-spatiotemporal-resolution neuroimaging in the brain cortex in the future. In addition, the advanced imaging technique developed in this program will find a diverse range of applications, including nanotechnology and molecular biology. Finally, this program will train 3 Ph.D., 1 M.Sc., and 10 summer students. Gaining valuable expertise ranging from optical engineering to neuroscience applications, these highly qualified personnel will contribute their knowledge in areas of photonics, medical physics, and biochemistry that are critical for Canada's future success in the global knowledge-based economy.

神经科学的一个普遍目标是记录在各种空间和时间尺度上的快速自发神经活动。常规电生理学依靠微电极来记录神经元的膜电位。但是，总的来说，这种侵入性方法在记录站点的数量中受到限制，容易受到环境电气噪声的影响，并且对纵向监测受到挑战。另一方面，光学记录已成为一种有吸引力的方法，可以在非侵入性，记录并行性和时空可扩展性方面具有固有的优势来衡量神经活动。光电压成像包括两个主要成分：电压指示器和光学成像仪器。生物化学的最新进展已实现了快速响应，高敏感性荧光电压指标。但是，现有的光学仪器仍然缺乏足够的速度，可扩展性和灵敏度。因此，尚未实现对神经活动的实时多尺度光学成像。 该发现程序的总体目标是开发独特的成像技术和设备，以实时多尺度的光学神经影像学。我们的长期目标是绘制大脑的功能连接组。在接下来的五年中，我们提出了三个项目，以协作努力调查技术开发和神经科学应用的光电压成像。具体而言，这些项目的目标 （1）开发用于实时的多尺度光电压成像的压缩超快显微镜（库存） （2）研究轴突初始节段和兰维尔节点在病理条件下使用库姆克在10 kHz2 MHz的情况下的生物物理特性 （3）确定使用110 kHz的库库来自由表现动物的神经编码和神经塑性 提出的程序的结果将通过显着增强我们从细胞生物水平到生物水平的神经元的成像能力来代表生物素化学的独特贡献。最先进的累积系统将极大地帮助神经科学家理解神经元生物物理学，电路神经科学和行为输出的开放问题。 Cumic还将为将来的脑皮质中的实时高速分辨率神经影像铺平道路。此外，该程序中开发的先进成像技术将发现多种应用，包括纳米技术和分子生物学。最后，该课程将培训3博士学位，1硕士和10名夏季学生。这些高素质的人员将获得从光学工程到神经科学应用的宝贵专业知识，将在光子学，医学物理学和生物化学领域贡献他们的知识，这对于加拿大在全球基于知识的经济中的未来成功至关重要。