In the brain of a single fruit fly, nerve cells are intertwined with each other to enable flight, mating, eating, sleeping, and all other activities in a fly’s life. Currently, with nine papers published on October 2nd, naturescientists report: The first complete map of her neurons — all 139,255 people, to be exact — and their 54.5 million connections.
This whole-brain map, painstakingly and precisely tracked over many years, is small but sophisticated. It houses 149.2 meters of neural wiring, all neatly packed into a brain the size of a poppy seed. This map thus shows how neural information flows between cells. Drosophila melanogasteran animal simpler than humans but complex enough that its brain remains a mystery to those trying to understand it.
“This study is really interesting,” says Olaf Spons, a neuroscientist at Indiana University in Bloomington. Back in 2005, he and his colleagues coined the term “connectome” to describe the connections between nerve cells or neurons (SN: February 7, 2014). In the nearly 20 years since then, scientists have mapped even more connectomes, including those of males and hermaphrodites. C.Elegance insects, fruit fly larvae, small pieces of mouse and human brains, and parts of adult fruit fly brains (SN: 3/9/23; SN: 19/8/7; SN: 5/23/24). This latest Drosophila connectome is the largest of its kind.
“When connectomics first started, creating maps like the one presented in this study seemed almost science fiction,” Spons says. “And now, amazingly, it’s here.”
The project involved electron microscopy images of more than 7,000 thin slices of a female Drosophila brain and machine learning to align intricate tendrils of neurons and track cells through the different slices. Machine learning has given researchers access to the entire connectome. “But humans still need to correct errors,” says Sven Dorkenwald, a computational neuroscientist who worked on the project at Princeton University and now works at the Allen Institute for Brain Science and the University of Washington in Seattle. . Hundreds of people in more than 50 labs calibrate the maps with human eyes to ensure the cells are shaped as they appear. It was a big job from start to finish.
“Did you think it would take this long to complete the fly connectome, almost 20 years later? Probably not,” says Sebastian Sun, a computational neuroscientist at Princeton University. “But overly optimistic people drive progress.”
In the early days, creating connectome maps was “a contrarian endeavor,” says Soong. “Most people thought it was crazy. There were two arguments against it: one, it wasn’t possible, and two, even if it was successful, the data wouldn’t be useful.”
But the data has already proven its usefulness, revealing intriguing hints about cellular details and how the brain works. For example, there are only two CT1 neurons in the entire fly brain, each involved in sensing changes in light and movement. Each neuron is spread throughout the eye, forming a huge number of synapses (more than 148,000, according to the map).
Another analysis divided some neurons into classes called “integrators,” which receive vast numbers of messages from other cells, or “broadcasters,” which send signals to large audiences. These megaphone cells may help spread the signal in a selective manner.
Now, with the connectome mapped, scientists began building computer models that show how information flows in the brain. “We start with the connections between neurons and use that to build a simulation of the network,” Seung says. “It’s a completely obvious approach, but we couldn’t do it without the connectome.”
For example, one new study shows how taste neurons can activate other downstream cells. And that’s just the beginning, says Soong. “The joke for science fiction enthusiasts is that we had to sacrifice one fly for this experiment, but this fly can live forever in the simulation.”
Mr. Spons is also looking to the future. “I foresee a future in which connectome maps will become even more comprehensive and detailed, and soon include the brains of vertebrates such as mice and humans,” he says. These maps will help answer big questions about the brain connectome, including whether it changes between individuals, over time, and whether it can help predict behavior.
