U.S. researchers have manipulated neurons in mice to light up in a rainbow of fluorescent hues, creating a powerful tool for mapping out the brain's complicated wiring plan, they said on Wednesday.
This "Brainbow," as they call it, will allow researchers to trace neurons throughout the nervous system, gaining new understanding of its organization and function.
"It has been exceedingly hard to figure out these wiring diagrams," said Joshua Sanes, professor in the Department of Molecular and Cellular Biology and Center for Brain Science at Harvard University. "That could be a main use of this."
Sanes said the Brainbow tool opens the door to research on diseases such as autism, mental retardation, bipolar disorder and even learning disabilities that may be related to wiring problems in the brain.
"There is more and more reason to imagine a lot of diseases of behavior are diseases of those circuits," he said.
The study, which appears in the journal Nature, was led by Harvard postdoctoral fellow Jean Livet. It draws its inspiration from the jellyfish Aequorea victoria, which has a gene that makes a glowing green fluorescent protein.
Researchers have figured out how to splice this gene into laboratory mice to make only their neurons glow. At first, they only glowed green. But others have tinkered with the gene to create hues of red, yellow and blue.
Now, Livet has figured out how to mix and match these colors to create roughly 90 bright hues that form a riotous display. He used a genetic recombination system known as Cre/lox to arrange the genes that encode the colored proteins, lighting up only nerve cells in mice.
"By using this so-called Cre system, what you do is essentially shuffle the colors in a different way in every cell so that different ones come out first. That is what gives you all of the colors," Sanes, who worked on the study, said in a telephone interview.
"This molecular trickery is kind of like a slot machine," Sanes said. "If you pull the handle exactly the same way, one time it will come up cherry, orange, lemon. And another time it will be lemon, lemon, lemon."
This produces a multicolored effect in the nervous system, which can help researchers follow the wiring plan.
"If you had a computer cable with 100 wires and you had to trace them out and they were all the same color, it would be nearly impossible," Sanes explained. "But if the wires are 100 different colors, it would be pretty easy to follow them to see where they go and how they branch."