“Brenner realized that to understand the nervous system you had to know its structure,” said Scott Emmons, a neuroscientist and geneticist at Albert Einstein College of Medicine, who later used digital techniques to create new C. elegans connectomes. “And that’s true across biology. Structure is so important.”
Brenner and his colleagues published their landmark paper, which clocked in at 340 pages, in 1986.
But the field of modern connectomics did not take off until the 2000s, when advances in imaging and computing finally made it feasible to map the connections in larger brains. In recent years, research teams around the world have started assembling connectomes of zebrafish, songbirds, mice, humans and more.
When the Janelia Research Campus opened in 2006, Gerald Rubin, its founding director, set his sights on the fruit fly. “I don’t want to offend any of my worm colleagues, but I think flies are the simplest brain that actually does interesting, complex behavior,” Dr. Rubin said.
Several different teams at Janelia have embarked on fly connectome projects in the years since, but the work that led to the new paper began in 2014, with the brain of a single, five-day-old female fruit fly.
Researchers cut the fly brain into slabs and then used a technique known as focused-ion beam scanning electron microscopy to image them, layer by painstaking layer. The microscope essentially functioned like a very tiny, very precise nail file, filing away an exceedingly thin layer of the brain, snapping a picture of the exposed tissue and then repeating the process until nothing remained.