Using Genetically Encoded Voltage Indicators (GEVIs) to Study the Input-Output Transformation of the Mammalian Olfactory Bulb

Genetically encoded voltage indicators (GEVIs) are fluorescent protein reporters of membrane potential. These tools can, in principle, be used to monitor the neural activity of genetically distinct cell types in the brain. Although introduced in 1997, they have been a challenge to use to study intact neural circuits due to a combination of small signal-to-noise ratio, slow kinetics, and poor membrane expression. New strategies have yielded novel GEVIs such as ArcLight, which have improved properties. Here, we compare the in vivo properties of ArcLight with Genetically Encoded Calcium Indicators (GECIs) in the mouse olfactory bulb. We show how voltage imaging can be combined with organic calcium sensitive dyes to measure the input-output transformation of the olfactory bulb. Finally, we demonstrate that ArcLight can be targeted to olfactory bulb interneurons. The olfactory bulb contributes substantially to the perception of the concentration invariance of odor recognition.