While scientists have a variety of tools on hand to monitor and manipulate living brains, they still lack the ability to observe how large numbers of individual neurons operate in real time. Now, researchers at the Howard Hughes Medical Institute have developed a remarkable technology, published in the journal Science, that illuminates neurons just as they fire off. The technology has already allowed the team to investigate the activity within the brains of mice, flies, and zebrafish.
The technology pairs a novel high-brightness fluorescent dye with a special protein that can be genetically introduced into the animals being studied. The injected dye pairs up with the protein, which is made to be produced by neurons, and the dye lights up whenever the neuron is active. The intensity of the glow is proportional to the voltage across the cell and individual neural cells can be seen blinking under the microscope as they do their routine work.
Because the imaging is performed in real-time and can be easily monitored, a variety of experiments can be performed while watching neural activity in the brain. Previous methods relied on slow, dim fluorescent molecules that provided poor temporal and spatial resolution. The new Voltron system, as it is called, uses a dye that is an order of magnitude brighter than older dyes.
The Howard Hughes researchers are already making Voltron available to other scientists and they hope to improve it further by making it compatible with two-photon imaging, a high-resolution imaging technique. Currently Voltron only works with light-sheet and other more conventional optical microscopes.
Top image: Voltron makes neurons fluoresce under the microscope. When the cell voltage changes, so does the fluorescence. That lets scientists know when neurons are firing. Credit: Ahmed Abdelfattah Side image: Voltron makes neurons in zebrafish brains glow. Credit: Ahmed S. Abdelfattah et. al/Science 2019. Supplemental figure S13.
The study in journal Science: Bright and photostable chemigenetic indicators for extended in vivo voltage imaging