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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=752660
• 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实时记录在不同空间和时间尺度上发生的快速、自发的神经活动。传统的电生理学依靠微电极记录神经元的膜电位。然而，一般来说，这种侵入性方法在记录地点的数量上是有限的，容易受到环境电噪声的影响，并且在纵向监测方面受到挑战。另一方面，光学记录已成为测量神经活动的一种有吸引力的方法，具有非侵入性、记录并行性和时空可扩展性等固有优势。光学电压成像包括两个主要组成部分：电压指示器和光学成像仪器。生物化学的最新进展使快速反应、高灵敏度的荧光电压指示器成为可能。然而，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，神经活动的实时、多尺度光学成像尚未实现。这个发现项目的总体目标是为实时、多尺度光学神经成像开发独特的成像技术和设备。我们的长期目标是绘制大脑的功能连接体。在接下来的五年里，我们提出了三个项目，从技术发展和神经科学应用的合作努力来研究光学电压成像。具体而言，这些项目的目标是：(1)开发用于实时，多尺度光学电压成像(2)在体外病理条件下使用10khz2 MHz的CUMIC研究轴突初始段和Ranvier节点的生物物理特性(3)在自由行为动物中使用110khz的CUMIC来确定神经编码和神经对感觉刺激的可塑性生物的水平。最先进的CUMIC系统将极大地帮助神经科学家理解神经生物物理学、电路神经科学和行为输出方面的开放性问题。CUMIC还将为未来大脑皮层的实时高时空分辨率神经成像铺平道路。此外，该计划开发的先进成像技术将有广泛的应用，包括纳米技术和分子生物学。最终，该项目将培养3名博士，1名硕士和10名暑期学生。获得从光学工程到神经科学应用的宝贵专业知识，这些高素质的人才将在光子学、医学物理学和生物化学领域贡献他们的知识，这些知识对加拿大未来在全球知识经济中的成功至关重要。