Computational Miniature Mesoscope for Cortex-wide, Cellular resolution Ca2+ Imaging in Freely Behaving Mice

用于自由行为小鼠皮层范围、细胞分辨率 Ca2 成像的计算微型介观镜

• 批准号: 10592331
• 负责人: Lei Tian
• 金额: $ 41.25万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592331
• 关键词: Address; Algorithms; Animals; Area; Behavior; Behavioral; Benchmarking; Biological; Brain; Brain region; Cells; Cognition; Cognitive; Complex; Data; Fluorescence Microscopy; Goals; Head; Histologic; Image; Individual; Joints; Lighting; Measurement; Measures; Mental disorders; Miniaturization; Motivation; Motor; Mus; Neurodegenerative Disorders; Neurons; Neurophysiology - biologic function; Neurosciences; Optics; Perception; Performance; Public Health; Recovery; Resolution; Sensory; Social Behavior; Social Interaction; Structure; System; Techniques; Technology; Testing; Three-Dimensional Imaging; Tissues; Training; Visualization; Weight; Work; brain tissue; deep learning; design; experimental study; imaging capabilities; imaging platform; improved; in vivo; in vivo imaging; innovation; lens; long term memory; meetings; multidisciplinary; multisensory; neural; neural circuit; neurotransmission; new technology; novel; olfactory bulb; preservation; prototype; real-time images; social; wearable device

ABSTRACT Perception and cognition arise from the coordinated activity of large networks of neurons spanning diverse brain areas. Understanding their emergent behavior requires large-scale activity measurements both within and across regions, ideally at single cell resolution. An integrative understanding of brain dynamics requires cellular-scale data across sensory, motor, and executive areas spanning more than a centimeter. In addition, functional interactions between brain areas vary with motivational state and behavioral goals, making data from freely moving animals particularly critical. Thus, a key goal is the ability to measure activity across the full extent of cortex at cellular resolution as animals engage in complex, cognitively demanding behaviors. However, conventional fluorescence microscopy techniques cannot meet the joint requirements of FOV, resolution, and miniaturization. Here, we propose a Computational Miniature Mesoscope (CM2) that will enable cortex- wide, cellular resolution Ca2+ imaging in freely behaving mice. The premise is that computational imaging leverages advanced algorithms to overcome limitations of conventional optics and significantly expand imaging capabilities. In our proof-of-principle system, we demonstrated single-shot 3D imaging across an 8x7mm2 FOV and 7µm resolution in scattering phantoms (Sci. Adv. 2020), and achieved single-cell resolution on histological sections. Our wearable prototype has now demonstrated visualization of sensory-driven neural activity across the 4x4mm2 main olfactory bulb in both head-fixed and freely moving mice. In this project we will: (Aim 1) advance CM2 hardware to achieve cortex-wide cellular resolution imaging. We will validate the hardware improvement on both phantoms and in vivo experiments. (Aim 2) Develop scattering-informed deep learning for fast and robust recovery of neural signals. We will validate the algorithm on in vivo experiments and benchmark against tabletop 1P and 2P measurements. (Aim 3) Cortex-wide, cellular-resolution Ca2+ imaging during social recognition in freely behaving mice. We will use CM2 to investigate the cross-area, network-scale activity dynamics that guide social interactions between familiar partners - one of the most integrative, multi-sensory, and cognitively demanding forms of neural processing. IMPACT ON PUBLIC HEALTH: This work will establish powerful enabling technology that greatly expands the scale of activity measurements possible in behaving animals, providing access to a wide range of questions about distributed cortical function. As a focused application, we will test the neural signatures of individual recognition during social behavior. We anticipate that our approach can be extended to a broader range of biological questions such as navigation, short- and long- term memory storage, and can potentially lead to new strategies for characterizing the disruptions in neural function that occur in psychiatric disease and neurodegenerative disorders.

摘要 感知和认知来自于跨越不同大脑的大型神经元网络的协调活动 地区了解它们的紧急行为需要在内部和跨内部进行大规模的活动测量 区域，理想情况下为单细胞分辨率。对大脑动力学的综合理解需要细胞尺度 数据横跨感官、运动和执行区域，跨度超过一厘米。此外，功能 大脑区域之间的相互作用随着动机状态和行为目标而变化，使数据自由地 移动动物尤其重要。因此，一个关键的目标是能够衡量整个范围内的活动， 当动物从事复杂的、对认知要求很高的行为时，大脑皮层的细胞分辨率。然而，在这方面， 传统的荧光显微镜技术不能满足FOV、分辨率和 小型化在这里，我们提出了一个计算微型显微镜（CM 2），将使皮层- 宽，细胞分辨率Ca 2+成像在自由行为的小鼠。前提是计算成像 利用先进算法克服传统光学器件的局限性并显着扩展成像 能力的在我们的原理验证系统中，我们展示了在8x 7 mm 2 FOV范围内的单次拍摄3D成像 和7μm的分辨率在散射幻影（Sci. Adv. 2020），并在组织学上实现了单细胞分辨率 路段我们的可穿戴原型现在已经展示了感官驱动的神经活动的可视化， 头部固定和自由活动小鼠的4 × 4 mm 2主嗅球。在本项目中，我们将：（目标1） 先进的CM 2硬件，以实现皮层范围的细胞分辨率成像。我们将验证硬件 改进了体模和体内实验。(Aim 2）开发分散信息的深度学习， 神经信号的快速和鲁棒恢复。我们将在体内实验和基准测试中验证该算法 对照桌面1 P和2 P测量。(Aim 3）社交期间的全皮层、细胞分辨率Ca 2+成像 在自由行为的小鼠中识别。我们将使用CM 2来调查跨区域、网络规模的活动 引导熟悉的伙伴之间的社会互动的动态-最综合的，多感官的， 和对认知要求很高的神经处理形式。对公共卫生的影响：这项工作将建立 强大的使能技术，极大地扩展了行为活动测量的规模。 动物，提供了一个广泛的问题，分布皮层功能。作为聚焦的 应用程序，我们将测试在社会行为过程中个体识别的神经特征。我们预计 我们的方法可以扩展到更广泛的生物学问题，如导航，短期和长期， 术语记忆存储，并可能导致新的战略，为表征中断的神经 发生在精神疾病和神经退行性疾病中的功能。