Voltage imaging in the olfactory bulb using transgenic mouse lines expressing the genetically encoded voltage indicator ArcLight

Abstract

Genetically encoded voltage indicators (GEVIs) allow optical recordings of membrane potential changes in defined cell populations. Transgenic reporter animals that facilitate precise and repeatable targeting with high expression levels would further the use of GEVIs in the in vivo mammalian brain. However, the literature on developing and applying transgenic mouse lines as vehicles for GEVI expression is limited. Here we report the first in vivo experiments using a transgenic reporter mouse for the GEVI ArcLight, which utilizes a Cre/tTA dependent expression system (TIGRE 1.0). We developed two mouse lines with ArcLight expression restricted to either olfactory receptor neurons, or a subpopulation of interneurons located in the granule and glomerular layers in the olfactory bulb. The ArcLight expression in these lines was sufficient for in vivo imaging of odorant responses in single trials using epifluorescence and 2-photon imaging. The voltage responses were odor-specific and concentration-dependent, which supported earlier studies about perceptual transformations carried out by the bulb that used calcium sensors of neural activity. This study demonstrates that the ArcLight transgenic line is a flexible genetic tool that can be used to record the neuronal electrical activity of different cell types with a signal-to-noise ratio that is comparable to previous reports using viral transduction.

Conserved Amino Acids Residing Outside the Voltage Field Can Shift the Voltage Sensitivity and Increase the Signal Speed and Size of Ciona Based GEVIs

“…ArcLight-derived GEVIs convert a voltage-induced conformational change of the protein into an optical signal allowing the visualization of neuronal circuit activity ( Borden et al, 2017 ; Platisa et al, 2022 ). This mechanism involves the movement of the VSD ( Siegel and Isacoff, 1997 ; Dimitrov et al, 2007 ; Villalba-Galea et al, 2009 ), the photophysical properties of the FP domain ( Kang and Baker, 2016 ; Kang et al, 2021 ), the linker region connecting the VSD to the FP ( Jung et al, 2015 ; Lee et al, 2017 ) as well as potential interactions between neighboring GEVIs via the dimerization of the VSD ( Rayaprolu et al, 2018 ; Leong et al, 2021 ).…”

Imaging different cell populations in the mouse olfactory bulb using the genetically encoded voltage indicator ArcLight

“…Surprisingly, few of the studies examining sensory coding in the mouse OB have been carried out using voltage imaging. 63 , 148 , 150 , 165 , 179 In addition to providing a direct readout of changes in membrane potential from genetically defined cell populations, voltage imaging can measure fast changes in neural activity that would be otherwise obscured when measured using slower imaging methods, and in principle, should be able to measure depolarizing and hyperpolarizing signals. Together, these advances may eventually provide clearer insight into fast temporal coding, and the nature of the inhibitory circuits within the OB.…”

Bioelectricity in Developmental Patterning and Size Control: Evidence and Genetically Encoded Tools in the Zebrafish Model

“…For example, multiple studies have shown the utility of genetically encoded indicators in fruit flies, but have, thus far, only been focused on neuronal-related studies [ 167 , 169 , 176 , 177 , 178 ]. In mice, fewer research studies have utilized GEVIs in vivo, and most of these studies focused on neurological research [ 178 , 179 , 180 , 181 , 182 ]. In addition, Xenopus oocytes were used to characterize Arclight, but did not address any developmental biology [ 183 ].…”