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

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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.