This Project Grant from the National Institutes of Health's National Institute of Neurological Disorders and Stroke will fund the development of advanced tools for genetically targeted all-optical electrophysiology in behaving mice. Specifically, the $4,381,836 award to President and Fellows of Harvard College, doing business as Harvard University, will support efforts to co-develop two-photon excitable genetically encoded voltage indicators and a new type of two-photon voltage-imaging microscope. Key activities include developing improved molecular reporters of membrane voltage compatible with two-photon excitation, screening microbial rhodopsin scaffolds and targeted mutations to enhance two-photon voltage sensitivity. Additionally, the award will enable development of a new high-speed scanning approach capable of visiting over 500 points in under 1 millisecond. The funding will also support establishing protocols for functional connectivity mapping, microcircuit dynamics measurements, and dendritic integration analysis in vivo. The work directly supports the CFDA 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders program's goal of advancing understanding of brain structure and function.
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