Miniature, integrated and mass-producible fluorescence microscopes for in vivo brain imaging in freely behaving rodents

Project Summary There is increasing awareness that aberrant neural circuit activity is a core manifestation of many neuropsychiatric diseasesincluding autismschizophreniadepression and Alzheimerandapos s diseaseThis realization has opened tantalizing prospects for more powerful and precise therapeutic approaches based on retuning of abnormal circuit activityHoweverwe still lack crucial 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 visualizing activity in large populations of genetically identified neurons in the brains of behaving animal subjectsInscopixIncspun out of Stanford University to commercialize a miniature fluorescence microscope technology that lets neuroscientists visualize Cadynamics in up toneurons simultaneously in awakebehaving rodents at cellular resolutionThe microscope is easily carried on the head of a mouse or ratand enables continuous recording from the same group of neurons in a single animal for periods of days to weeksUsed in conjunction with genetically encoded Caindicators and our custom designed optical microendoscope probesthe microscope enables targeting of predefined neuronal subpopulationsand entry to brain regions inaccessible to other large scale recording technologiesIn Phase Iwe developed and validated a new version of the microscope that is substantially higher performing and more robust than the original Stanford prototypeAround it we built the nVista imaging systeman end to end solution for in vivo brain imaging that includes the miniature microscope with an integrated HD camera and electronicsand user friendly data acquisition hardware and softwareThe nVista system has now been disseminated for beta testing to overlabs around the globeThis Phase II project will move the nVista system forward in its next steps towards marketing to the general neuroscience communitythrough the following aimsCreate a next generation version of the nVista system for commercial disseminationMaking use of feedback from early adopterswe will refine the systemandapos s design for greater performancereliability and ease of useby incorporating an electronic focusing mechanismenabling higher speed data acquisition and seamless interfacing with other data collection systemsExtend the technology to rats by developing an accessory array for the nVista microscope that includes a new base plate attachment mechanismprotective head mounted cone and cable sheathingoptical probesand an optical data link to support commutatorsandDevelop a next generation data analysis platform with faster processingcustomizabilityand better visualization tools Project Narrative This grant will further develop and refine a revolutionary miniature microscope technology to observe and investigate the thinkingworking brain in animal subjects at the level of its neural circuitspopulations of brain cells that control specific functionsThe technology we develop and ready for future commercialization has the potential to transform our understanding of how the brain works in healthand how it malfunctions in human brain disorders including psychiatric disorders that involve abnormalities in large scale brain function such as schizophreniadepressionattention deficit disorderand autism