RII Track-4:NSF: Investigating Functional Neuronal Connections between Sensory and Motor Cortex using 3D Mesoscopic Optical Imaging Technique and Three-photon Microscopy

非技术描述：了解大脑如何工作将提高治疗各种精神和神经疾病的能力。该项目将为俄克拉何马大学的一名助理教授提供奖学金，并为一名研究生提供培训，并将使用一种新颖且经济高效的介观成像技术对活小鼠进行功能性脑成像。此外，该项目将利用康奈尔大学的尖端显微镜来验证这种成像技术，并进一步研究大脑回路。该研究人员将与一名博士生一起在康奈尔大学的主办实验室进行为期6个月的访问，以启动研究合作。经过验证的介观成像平台有可能对现有成像系统进行重大改进，并将成为神经科学家在体内研究小鼠皮层神经活动的有力工具。此外，这个经过验证的成像平台可以广泛用于研究许多神经系统疾病，如阿尔茨海默病，并有助于制定更好的诊断和治疗策略。通过这项奖学金，研究人员将学习和掌握这些尖端的显微镜技术，并将这些知识带回俄克拉何马大学，使50名研究人员受益，从而提高俄克拉何马州的研究能力。技术描述：哺乳动物皮层的神经回路在高级脑功能中起着重要作用。由于小鼠皮层的厚度有限（分为6个水平层，深度约为1mm）和不同皮层区域之间的距离（约为几毫米），目前采用的大多数脑功能成像方法无法充分研究皮层内层间的相互作用。这是由于以下主要限制中的至少一个：有限的视场，较浅的穿透深度，有限的空间和/或时间分辨率。为了研究小鼠皮层和体内不同皮层区域之间的三维（3D）层特异性相互作用，研究人员开发了一种新的介观成像技术，该技术可以实现~30-100 μ m的分辨率，成像深度为毫米。另一方面，三光子显微镜的最新进展使得通过小鼠皮层进行结构和功能成像成为可能。本课题的研究目的是：1)利用康奈尔大学最先进的三光子显微镜验证这种新型介观三维成像方法；2)研究在须状感觉运动电路中，层特异性投射的功能后果。除了验证介观成像系统外，该研究还可能通过结合先进的成像方法和光遗传控制策略来帮助揭示体感觉皮层和光遗传控制策略之间的层特异性神经功能连接。这些新颖的成像平台将使神经科学家能够研究活体动物不同皮质区域的3D神经连接。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Non-technical Description:Understanding how the brain works will improve the ability to treat a variety of mental and neurological diseases. This project will provide a fellowship to an Assistant Professor and training for a graduate student at the University of Oklahoma and will use a novel and cost-efficient mesoscopic imaging technique for functional brain imaging in living mice. Additionally, the project will take advantage of the cutting-edge microscopy at Cornell University to validate this imaging technique and further investigate the brain circuit. The researcher along with one Ph.D. student will spend a 6-months visit to the host lab at Cornell University to initiate research collaborations. The validated mesoscopic imaging platform has potential to provide a significant improvement over the current imaging system and will become a powerful tool for neuroscientists to investigate the neural activities in the mouse cortex in vivo. Furthermore, this validated imaging platform can be broadly used to study numerous neurological disorders, such as Alzheimer’s disease, and aid in devising better diagnostic and treatment strategies. Through this fellowship, the researcher will learn and master these cutting-edge microscopy techniques and bring this knowledge back to the University of Oklahoma to benefit 50 researchers—thus enhancing the research capability in Oklahoma. Technical Description:The neural circuits in the mammalian cortex play important roles in higher brain function. Due to the limited thickness of the mouse cortex (organized in 6 horizontal layers in ~1 mm depth) and the distance between different cortical areas (~ several millimeters), most of the currently employed methods for brain functional imaging are unable to adequately study the layer-specific interactions within the cortex. This is due to at least one of the following major limitations: limited field of view, shallow penetration depth, limited spatial and/or temporal resolution. To investigate the three-dimensional (3D) layer-specific interaction in the mouse cortex and between different cortical areas in vivo, the researcher developed a novel mesoscopic imaging technique that can achieve a resolution of ~30-100 µm with millimeters imaging depth. On the other hand, recent advances in three-photon microscopy have made it possible to image through the mouse cortex for both structural and functional imaging. The research objective of this proposal is to: 1) validate this novel mesoscopic 3D imaging method using the state-of-art three-photon microscopy at Cornell University; and 2) investigate the functional consequences of the layer-specific projections in whisker sensorimotor circuit. In addition to validating the mesoscopic imaging system, the study has potential to help uncover the layer-specific neural functional connections between the somatosensory cortex and primary motor cortex by combining both the advanced imaging methods and optogenetic control strategy. These novel imaging platforms will enable neuroscientists to investigate the 3D neural connections across different cortical regions of live animals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.