'Voltron' captures live brain cell action


Rebecca Pool

Monday, August 5, 2019 - 21:00
Image: Novel genetically-encoded fluorescent voltage indicator tracks neurons in living animals [Ahmed Abdelfattah].
US-based researchers have developed a genetically-encoded fluorescent voltage indicator to target specific brain cells and track neural activity in living animals for longer time periods than was previously possible. 
So-called Voltron combines a novel fluorescent dye with an engineered multi-part protein that alters the dye's intensity when specific neurons are switched on.
Voltron allows researchers to detect neural signals throughout the brain and has already been adopted by more than one hundred laboratories around the world.
Voltron makes neurons in zebrafish brains glow. [Ahmed S. Abdelfattah et. al/Science 2019. Supplemental figure S13.]
As Professor Eric R. Schreiter from the Howard Hughes Medical Institute's Janelia Research Campus and colleagues highlight in Science, imaging changes in membrane potential using genetically encoded fluorescent voltage indicators has huge potential for monitoring neuronal activity with high spatial and temporal resolution.
However, brightness and photostability of fluorescent proteins and rhodopsins have limited the utility of the existing indicators. 
Given this, the researchers engineered Voltron, which uses bright and photostable synthetic dyes instead of the usual protein-based fluorophores.
Their new indicator extends the combined duration of imaging and number of neurons imaged by more than tenfold relative to existing genetically encoded fluorescent voltage indicators. 
Crucially, the researchers have demonstrated Volton for in vivo voltage imaging in mice, zebrafish, and fruit flies.
For example, in the mouse cortex, Voltron allowed single-trial recording of spikes and subthreshold voltage signals from dozens of neurons simultaneously, over 15 min of continuous imaging.
Meanwhile, in larval zebrafish, the indicator could precisely correlate neuron spike timing with behaviour. 
Mouse neurons (yellow dots) are labelled using Voltron. The overlay shows voltage signals measured using the tool; spikes indicate a cell has sent a message. [Ondrej Novak]
In lab tests using Voltron, HHMI Investigator Adam Cohen was able to watch neurons light up in the spinal cord of developing zebrafish.
“It was very exciting to see neural activity in real time,” says Cohen, who is based at Harvard University and was not involved in the study. 
Schrieter and colleagues can currently use Voltron with light-sheet microscopy and other light microscopes, but would now like to develop a Voltron variation that works with two-photon imaging. 
Research is published in Science and bioRxiv.
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