Microscope system for large scale optical imaging of neuronal activity using kilohertz frame rates

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Abstract This project aims to develop the 2P-ActivityScope™, a revolutionary new microscope based on a technological breakthrough called second-generation Scanned Line Angular Projection (SLAP2) two photon laser scanning microscopy that was recently developed by Dr. Kaspar Podgorski (Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA). The game-changing innovation in the 2P-ActivityScope is the ability to perform unparalleled (i) optical imaging of neuronal activity in populations of neurons at subcellular spatial resolution and temporal resolution in the millisecond range both in vivo and in vitro using a variety of fluorescent indicators (e.g. voltage, [neurotransmitter]) as well as (ii) high-resolution volumetric calcium imaging of columns of cortical neurons at 40 Hz in vivo. These capabilities are crucial for ultimately decoding how information is represented and processed by the billions of densely interconnected neurons comprising the mammalian central nervous system. Neither contemporary 2-photon microscopes, functional magnetic resonance imaging, inserting electrodes into the brain, or fiber photometry can serve this need. This project will disseminate and improve upon the original, lab-built SLAP2 invention to create a commercial product for this important new technology. Based on pilot work performed at Janelia, it is clear that the 2P-ActivityScope will make a significant impact on the field of neuroscience research, including advancing studies focused on alterations in CNS circuitry associated with neurodevelopmental, neuropsychiatric and neurodegenerative disorders. Ultimately, this will result in an improved basis for developing novel treatment strategies for a wide spectrum of complex brain diseases. In Phase I we will demonstrate feasibility of this novel technology by developing prototype hardware and software; work in Phase II will focus on creating the full functionality of the 2P-ActivityScope for commercial release. We will perform extensive feasibility studies, product validation and usability studies of the 2P-ActivityScope in close collaboration with Dr. Podgorski and our academic collaboration partners. A competing technology is not commercially available.