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。该项目将为俄克拉荷马州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具有成本效益的介观成像技术对活体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。研究人员沿着一位博士。学生将花6个月的时间访问康奈尔大学的主机实验室，以启动研究合作。经过验证的介观成像平台有可能提供一个显着的改进，目前的成像系统，并将成为一个强大的工具，神经科学家在体内研究小鼠大脑皮层的神经活动。此外，这种经过验证的成像平台可广泛用于研究许多神经系统疾病，如阿尔茨海默病，并有助于设计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技术，并将这些知识带回俄克拉荷马州大学，使50名研究人员受益--从而提升俄克拉荷马州的研究能力。 技术描述：哺乳动物大脑皮层中的神经回路在高级大脑功能中起着重要作用。由于小鼠皮质的厚度有限（组织在6个水平层中，深度约为1 mm）和不同皮质区域之间的距离（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质内的层特异性相互作用。这是由于以下主要限制中的至少一个：有限的视场、浅的穿透深度、有限的空间和/或时间分辨率。为了研究小鼠皮层中以及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型介观成像技术，可以实现约30-100 µm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。这项提案的研究目标是：1）使用康奈尔大学最先进的三光子显微镜验证这种新的介观3D成像方法; 2）研究晶须感觉运动电路中特定于层的投影的功能后果。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学控制策略来帮助揭示躯体感觉皮层和初级运动皮层之间的层特异性神经功能联系。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层区域的3D神经连接。该奖项反映了NSF的法定使命，并通过使用基金会的智力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.