Enhanced Recording of Discharge Events by Localizing Genetically Encoded Voltage Indicators to the Neuronal Soma



Purwin, Ryan J

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Genetically Encoded Voltage Indicators (GEVIs) convert changes in the electrical potentials of cell membranes to changes in the intensity of fluorescence emission. Numerous types of GEVIs have been created and shown to track neuronal action potentials with high fidelity and a sufficient signal to noise ratio in cultured neurons and simple organisms. Problems have been encountered when even the best GEVIs have been expressed in complex mammalian circuits, the most concerning being a low signal-to-noise ratio resulting from cell-wide expression of the GEVI and high density and overlapping neural architectures from different cells. A way to rectify this issue is to restrict the surface expression of the GEVI to a specific neuronal compartment; for action potentials, the optimal compartment is the neuronal soma. Restriction of any GEVI to the neuronal soma can be achieved by fusing it to a soma-localizing motif. Differentiated PC12 cells transfected with our construct, FireFluo, have been shown to emit fluorescence that is largely contained in the soma. Future directions include soma localization of additional GEVI types, testing of soma-restricted GEVIs in complex circuits, and eventually tracking of thousands of neurons in behaving animals, leading to a better understanding of relationships between activity patterns in neural circuits and specific cognitive abilities.



Genetically encoded voltage indicators, Action potential, Hybrid optical voltage sensor, Fluorophore