Many cognitive processes, such as decision-making, take place within seconds or minutes. Neuroscientists have longed to capture neuron activity during such tasks, but that dream has remained elusive — until now.
A team of MIT and Stanford University researchers has developed a way to label neurons when they become active, essentially providing a snapshot of their activity at a moment in time. This approach could offer significant new insights into neuron function by offering greater temporal precision than current cell-labeling techniques, which capture activity across time windows of hours or days.
“A thought or a cognitive function usually lasts 30 seconds or a minute. That’s the range of what we’re hoping to be able to capture,” says Kay Tye, an assistant professor in the Department of Brain and Cognitive Sciences at MIT, a member of the Picower Institute for Learning and Memory, and one of the senior authors of the study.
Kay Tye envisions that this tool could be used to help decipher the neural circuits involved in learning and memory, among many other possibilities.
The researchers designed their tool to respond to calcium, because neurons experience an flux of calcium ions every time they fire an electrical impulse. However, the neurons are only labeled if this calcium flux occurs while the cell is also exposed to a beam of blue light delivered by the researchers.
Photo Credit: MIT
This combination of light exposure and calcium activity triggers the activation of a transcription factor that turns on a target gene that the researchers have engineered into the cells’ genome. This gene could encode a fluorescent protein or anything else that could be used to label or manipulate neurons.
In this study, the researchers demonstrated the technique, which they call FLARE, by turning on a red fluorescent protein called mCherry in the motor cortex neurons of mice as they ran on a treadmill.
This approach could also be used to label cells with light-sensitive proteins that would allow the targeted neurons to be controlled by optogenetics, or new proteins called DREADDS that allow neurons to be controlled using small-molecule drugs. Importantly, because all of the tool components can be delivered using viral vectors, this tool could be used in any model organism.
Kay Tye developed The technology is developed with former MIT Professor Alice Ting, who is now a professor of genetics and biology at Stanford and is also a senior author of the paper. The paper’s lead author is Wenjing Wang, a Stanford postdoc.