Researchers say they have created a complete map of an adult fruit fly, showing how almost 140,000 individual neurons are linked up to each other and turn sensory inputs into behavioral responses.
The connectome — basically, a wiring diagram that traces the connections between brain cells — is the subject of a flurry of research papers published today by the journal Nature.
It’s not the first such brain wiring diagram, or connectome, to be traced out: Previous projects have charted the brain of a roundworm (302 neurons), plus the brains of a larval sea squirt and a larval marine worm, as well as the brain of a larval fruit fly (3,016 neurons).
But the adult fruit fly connectome, encompassing 139,255 neurons and roughly 50 million connections — raises the bar considerably. And it’s getting scientists thinking about what it will take to achieve a similar feat focusing on the human brain.
“Any brain that we truly understand tells us something about all brains,” Princeton University neuroscientist Sebastian Seung, a leader of the research team, said today in a news release. “With the fly wiring diagram, we have the potential for an unprecedented, detailed and deep understanding.”
The fruit fly is widely used as a model in biological experiments, and even though its brain is minuscule when compared with the human brain — which has roughly 170 billion cells, half of which are neurons — there are lots of similarities in the operating instructions. Fruit flies can get drunk, can be kept awake with coffee, and can even compose courtship songs that are customized to their mates’ preferences.
To build their connectome, researchers started out with 21 million electron microscopy images of an adult female fruit fly’s brain. Artificial-intelligence modeling wove the data from those images into a sprawling map. Citizen scientists — including gamers — joined professional researchers in the FlyWire Consortium to “proofread” the AI-generated map. More than 3 million manual edits were made.
“What we built is, in many ways, an atlas,” said Sven Dorkenwald, the lead author of the project’s flagship paper. Dorkenwald earned his Ph.D. at Princeton last year and is now a research fellow at the University of Washington and the Allen Institute in Seattle.
“Just like you wouldn’t want to drive to a new place without Google Maps, you don’t want to explore the brain without a map,” Dorkenwald explained. “What we have done is build an atlas of the brain, and added annotations for all the businesses, the buildings, the street names. With this, researchers are now equipped to thoughtfully navigate the brain, as we try to understand it.”
Some of the researchers used a computerized model of the connectome to see how a simulated fly would respond to the taste of sugar water, or the sensation that it had dirt on its antennae. The model correctly predicted that the fly would extend its proboscis to start sipping the sugar water, or use its legs to groom its dirty antennae.
Phil Shiu — who worked on the project during his time at the University of California at Berkeley and is now a researcher at a brain-emulation startup called Eon Systems — said the model is still a work in progress. But it shows how studying the connectome of the adult fruit fly could open up wider frontiers in neuroscience.
“This really suggests that getting a mouse connectome, and eventually a human connectome, will be incredibly valuable. We can imagine a world where we can simulate a mouse brain, or eventually a human brain, and really get fundamental insights into the causes of various mental health disorders and about how the brain works,” Shiu said in a Berkeley news release.
Unraveling the mysteries of brain connectomes could also reveal new ways to create artificial neural networks for AI applications. “This is a real neural network,” Shiu said. “To AI people, it doesn’t matter what biology is doing because the techniques are somewhat different. But I think the idea of building computer models of the mouse brain and then eventually human brain is super-cool, and presents an alternate way of getting to really good AI that isn’t the conventional large language model path that is being pursued right now.”
This animation shows neurons in the taste network of the adult fly brain responding to sugar water and a liquid mixture of sweet and bitter. The cascade of neurons stimulated by sugar-sensing neurons ends up activating motor neurons that extend the proboscis to suck up the sugar water. But when bitter is mixed with sweet, inhibitory neurons stop the process, protecting the fly from possible poison. (Credit: Night of August Studios / Igor Lapshin)
For more about the FlyWire brain connectome, check out the FlyWire website and Nature’s portal page for the project. The FlyWire Codex provides access to data analysis tools for the full-brain connectome.
More atlases from the Allen Institute
The Allen Institute recently reported progress on two other cell-mapping initiatives:
- The Allen Institute for Immunology announced the release of its first Human Immune Health Atlas, a comprehensive single-cell reference dataset that offers insights into the landscape of healthy human immune cells from childhood through adulthood.
- The BRAIN Initiative Cell Atlas Network, or BICAN, launched its first major data release, marking a significant milestone in the ambitious effort to map the whole human brain. The data, accessible through the BICAN Rapid Release Inventory, includes single-cell and single-nucleus transcriptomic and epigenomic profiles from humans, mice and 10 other mammalian species. The Allen Institute is part of the network, which draws upon funding from the National Institutes of Health’s BRAIN Initiative.
