Next generation in vivo miniature microscopes integrating dual-color imaging, 3D imaging, and optogenetic stimulation with a cloud-compatible data acquisition platform

Project Summary Our understanding of neuropsychiatric disorders is undergoing a paradigm shift away from simple models emphasizing neurotransmitter imbalance towards more sophisticated theories based on abnormalities in neural circuit functionThis is especially important for understanding disorders like Schizophrenia and PTSDwhich defy simple biochemical explanationsbut are now known to involve abnormal patterns of neural ensemble activityEven for other types of brain disorders such as neurodegenerative disorderse gParkinsonandapos s Diseaseor neurodevelopmental disorderse gAutismthat have molecular geneticcellular or environmental causesthere is increasing awareness that the dysfunction is ultimately expressed at the level of neural circuits in the brainand manifests in abnormal neural circuit dynamicsHoweverwe still lack crucial basic understanding of neural activity patterns during normal behavior and how these patterns are altered in diseaseMany rodent models of human brain diseases are now availablebut neuroscientists are still hindered by lack of a technology for large scale recording and manipulation of activity in large populations of genetically identified neurons in the brains of behaving animal subjectsInscopixIncwas spun out of Stanford University to commercialize a miniature fluorescence microscope technology to enable neuroscientists to visualize Cadynamics in up toneurons simultaneously in awakebehaving rodents at cellular resolutionThe development of the commercial systemnVistawas partly funded by a prior NIMH SBIR grantThe project surpassed all expectations and exemplifies how the NIH NIMH SBIR program is highly effective in catalyzing innovation and supporting commercialization of breakthrough innovations for NeuroscienceThe outcome of the prior SBIR Phase I and Phase II is an nVista system that is today in use at overlaboratories around the world and that has led to andgtscientific publications in top tier journalsIn this Fast Track proposalwe will build on the prior successful SBIR and the success of nVistaand develop and commercialize a next generation brain mapping platform that transforms nVista into a versatile platform integrating singleand dual color imagingvolumetric imagingand optogenetics stimulation capabilitiestogether with web basedcloud compatible data acquisition and controlIn Phase Iwe will design and fabricate prototypes of the new microscope for the next generation brain mapping platformAimtogether with an advanced video data acquisition and processing systemAimWe will validate performance of these prototypes and conduct the first in vivo experiments with a small group of beta labsAimIn Phase IIwe will fabricatecompleteuser friendly systemsincorporating feedback from Phase IAimwith supporting image processing and analysis algorithmsAimWe will perform extensive in vivo experiments with a larger set of beta sites to demonstrate the scientific value of all featuresAimAt the end of Phase IIwe will have a new miniature microscope system that integrates singleand dual color imagingvolumetric imagingand optogenetics stimulation capabilitiestogether with web based data acquisition and control ready for mass production and commercialization to the Neuroscience communityThe new product will obsolete our current nVista and will become our flagship product enabling brain researchers around the world to causally link neural circuit activity to brain functionWe expect the new product to catalyze neural circuit research and to become a centerpiece of worldwide efforts to map brain circuit activity and to understand the brain in actionWe also expect the product to be broadly adopted by large research centers and by Pharmaexpanding the range of applications beyond basic Neuroscience to translational projects built around understanding brain disease and developing next generation treatments PROJECT NARRATIVE Understanding the circuits and patterns of neural activity that give rise to mental experience and behavioris an overarching goal of the BRAIN InitiativeNIHandapos s BRAINvision document has identified the development and dissemination of capabilities for large scale recording and modulation of neural dynamics as a critical need and the heart of the BRAIN InitiativeIn this Fast Track Proposalwe will build on our prior success in commercializing a head mounted miniaturized microscope based system that enables neuroscientists to record and monitor large scale neural dynamics at single cell resolution in freely behaving rodents over monthsTechnological innovation inspired by user feedback and the broader needs of the Neuroscience community will include integrating singleand dual color imagingand simultaneous optogeneticstogether with volumetricDimaging capabilities all in onenew next generation miniature microscopeWe will also develop a cloudcompatible data acquisition systemfacilitating streaming of data directly to the cloud and cloud based storage and processing of large brain data setsThis next generation integrated all optical platform will enable brain researchers around the world to causally link neural circuit activity to brain function and will become the centerpiece of worldwide efforts to map brain circuit activity and understand the brain in actionCloud based data acquisition and analysis will also be an enabling innovation for adoption by Pharma and Biotech to understand how neural circuit patterns go awry in brain diseaseswhich will in turn lead to the development of next generation circuit based therapeutics for diseases such as Parkinsonandapos s and Schizophrenia