This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: When researchers at HHMI's Janelia Research Campus set out to create a map of all the neurons in the fruit fly brain in 2008, many in the scientific community thought they were out of their minds. It had been 20 years since scientists had unveiled the wiring diagram—or connectome—of the 302 neurons in the tiny worm C. elegans, an effort that took more than a decade.
Most scientists thought mapping the fly brain, with more than 100,000 neurons, would take too long and cost too much—and they didn't think it would tell neuroscientists much about how the brain worked. But those skeptics didn't deter Janelia's founding executive director, Gerry Rubin. Instead, their skepticism fueled his bet that, through the development of better imaging and computational techniques, the research campus could reduce the cost and time needed to map all the neurons of a complex animal, creating a wiring diagram that would yield unprecedented insights into how the brain enables sophisticated behavior.
Today, that vision has come to fruition with the publication in Cell of the connectome of the full central nervous system of a fruit fly: a wiring diagram of more than 166,000 neurons that make up the fly's brain and ventral nerve cord and the millions of connections between them. Along the way, Janelia's pursuit of the fly connectome has transformed scientific research, revealing new insights into how the brain enables behavior, pioneering new technologies to empower biological discoveries and helping to launch the thriving field of connectomics. Now, Janelia is applying lessons learned in creating the fruit fly connectome to new animal models, with the ultimate goal of providing the first mechanistic account of how a vertebrate brain generates behavior.
"None of those things would've happened if we hadn't done the fly," says Rubin, now the head of biology and a senior group leader at Janelia. "It was us having the leap of faith that we could assemble an interdisciplinary team who would develop ways to increase the efficiency of generating connectomes by more than 1,000-fold. That was our key contribution, and without that, we could still be waiting." Soon after Janelia opened its doors, it became apparent that making a detailed wiring diagram of the fly brain lay at the intersection of its two areas of focus at the time: neuroscience and advanced imaging.
"We felt, which wasn't a universally accepted idea, that we wouldn't be able to understand the brain at a satisfying level without having a wiring diagram," Rubin says. "We knew it was possible; it was a well-defined problem. We just had to figure out how to do it." The team estimated that, with the technology available when they started, creating the fly connectome would take 500 people working for 10 years—a time and cost that needed to be reduced through technological improvements.
Researchers, led by senior group leader Harald Hess, spent years optimizing and scaling up a pioneering microscopy technique to get sharper and more detailed images of individual neurons. Other teams working with collaborators at Google Research developed computational methods to speed up image interpretation, eventually reaching the point where the connectome was feasible. "Janelia was just ideally set up to have the patience for developing these technologies, and I think it's been transformative not only for the fly connectome, but also many, many other applications," says Hess.
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