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

Douglas A Storace,Yunsook Choi,Lawrence B Cohen

doi:10.3389/fncel.2019.00342

Abstract

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.

Highlights

In the first section of the paper we show that both the Genetically encoded voltage indicators (GEVIs) and the voltage processes that they follow are faster than the Genetically Encoded Calcium Indicators (GECIs) and the calcium concentration changes that they follow
In the second section of the paper we describe the use of GEVIs and organic calcium dyes to determine the input-output transformation of the mammalian olfactory bulb
In the third section of the paper we demonstrate that ArcLight can be targeted to an olfactory bulb interneuron

Summary

Introduction

Traditional optical imaging techniques using intrinsic signals (Blasdel and Salama, 1986; Grinvald et al, 1986) or organic dyes for measuring voltage (Davila et al, 1973) and calcium (Brown et al, 1975; Tsien, 1980), have limited ability to distinguish the cell types contributing to the signal, except in a few special cases (Tsau et al, 1996; Wenner et al, 1996; Friedrich and Korsching, 1997; Wachowiak and Cohen, 2001). Encoded voltage indicators (GEVI) optically report membrane potential in targeted cell types. ArcLight is a GEVI that can detect action potentials in cultured mammalian neurons (Jin et al, 2012), in vivo in Caenorhabditis elegans (Wooltorton et al, 2013) and Drosophila (Cao et al, 2013), and population voltage signals in mice (Storace et al, 2015, 2016; Borden et al, 2017; Storace and Cohen, 2017). Bando et al (2019) compared ArcLight to other GEVIs and reported that ArcLight had the largest signal-to-noise ratio in both 1 and 2-photon imaging from the in vivo mouse brain ArcLight is a GEVI that can detect action potentials in cultured mammalian neurons (Jin et al, 2012), in vivo in Caenorhabditis elegans (Wooltorton et al, 2013) and Drosophila (Cao et al, 2013), and population voltage signals in mice (Storace et al, 2015, 2016; Borden et al, 2017; Storace and Cohen, 2017). Bando et al (2019) compared ArcLight to other GEVIs and reported that ArcLight had the largest signal-to-noise ratio in both 1 and 2-photon imaging from the in vivo mouse brain

Methods

Results

Conclusion