Genetically Encoded Activity Indicators

Selection and application of genetically encoded voltage indicators (GEVI) from the large palette of available options requires careful consideration between different indicator properties. A general issue that voltage imaging has to deal with in in vivo applications are the hemodynamic responses that add to the GEVI signal. With GEVIs that emit in the visual spectral range this confound is unavoidable and requires careful data analysis. Voltage imaging using GEVIs has steadily progressed over the last decade but much space for improvement remains. Needed are GEVIs with reduced photobleaching, increased response bandwidth and optimization for in vivo use. Most useful would be well performing GEVIs that operate in the near infrared spectrum. Initial attempts to generate practically useful GEVIs were based on a single fluorescent protein fused to a voltage gated ion channel. Most GEVI-based voltage imaging experiments in the mammalian brain are performed using mice in vivo or ex vivo.