In a major milestone for neuroscience, researchers have mapped the entire wiring of a fruit fly’s brain—marking the first time we’ve charted every neuron and its connections in an adult animal. This neural map, known as the connectome, details 139,255 neurons and 50 million synapses (the connections between these neurons), offering an unprecedented view of how neural circuits operate in a brain capable of vision and movement.
The fruit fly (Drosophila melanogaster) has long been a staple in research, and its newly unveiled brain map is expected to be a valuable tool in advancing knowledge of how neural circuits underlie behavior. But the team behind the project has even bigger ambitions. The hope is that similar techniques will one day be used to decode larger brains, even those of mammals.
Published today in Nature, the work comes from the FlyWire Consortium, an international group of over 76 labs from the UK, US, and around the world.
From Spaghetti to Salami: Mapping the Fly Brain
Dr. Sebastian Seung of Princeton University, one of the lead researchers, said that despite the fly brain’s small size, its complexity cannot be underestimated. “A fruit fly can see, smell, hear, walk, and fly,” Seung told ZME Science. “Flies socialize, navigate, and learn from experience.”
The fruit fly’s easier-to-study small brain yet complex behavior explains why these insects have been the go-to model for neuroscientists for decades. Previous research had only charted the brains of simpler creatures, like the nematode worm, which has just 302 neurons, or fruit fly larvae, with around 3,000 neurons. The adult fruit fly’s brain, by contrast, is much more complex, though still simple compared to mammals. However, mapping the connectome of even such a small brain nevertheless posed significant challenges.
Creating the connectome required immense computational power and herculean human effort. The process began by slicing a female fly brain into 7,000 sections, each just 40 nanometers thick—thinner than a human hair. Using high-resolution electron microscopy, the team generated over 100 terabytes of image data. That’s roughly equivalent to the storage capacity of 100 standard laptops. The data were then analyzed using artificial intelligence developed at Princeton University to identify the neurons and their connections.
“You can think of brain tissue as a tangled-up spaghetti of neural branches,” Seung said. From these images, the researchers traced each neuron’s path—an equivalent of about 150 meters of wiring. To put this in perspective, the human brain contains millions of miles of neural wiring. Seung joked that the process was akin to turning “brain spaghetti into brain salami.”
This effort would not have been possible without the use of an AI, which spotted key patterns in neurons and their connections to build the map. However, as you’re probably aware if you ever used an LLM like ChatGPT, the results are not always accurate. Hundreds of researchers, students, and even volunteers painstakingly reviewed the data and had to manually correct errors.
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This level of detail opens a new frontier in brain research. The connectome not only provides a static map of the fly brain but can also offer insights into how brains function in real time.
“One surprise is that the fly visual system is analogous to a convolutional net, the dominant approach to visual AI,” said Seung. “Using the connectome, one can now make very precise statements about the similarities and differences between the ways in which insects and computers see.”
Interconnected Networks and Individuality
For Dr. Mala Murthy of Princeton University, the most striking finding was the high level of interconnectedness within the fly brain. “I’ve worked on fly brains for nearly 25 years, and the wiring is much more complicated than I expected,” Murthy told ZME Science.
Yet, this surprising complexity also reveals an opportunity. By following the information flow through these connections, neuroscientists can begin to predict how brain activity relates to behavior.
“It is an exciting time for neuroscientists to have a complete map of the brain and begin to unravel how the map relates to function—both neural activity and behavior,” she noted.
Another key discovery was that, despite the complexity, brains are not as individually unique as previously thought. Dr. Philipp Schlegel, from the University of Cambridge, explained that the wiring patterns in one fly’s brain were nearly identical to those in another.
“Insect brains are highly stereotyped—you can typically find the same neuron from individual to individual just based on its shape,” Schlegel said. The researchers did find rare instances where neurons seemed to make “wrong turns” but eventually ended up in the correct part of the brain. This suggests that precise wiring is crucial to proper brain function, though some variation may still occur without affecting overall behavior.
This finding challenges the idea that brains are as unique as fingerprints. Instead, it suggests a level of uniformity in how neurons are wired — something that could have implications for studying brain disorders, where incorrect wiring could lead to malfunction.
The Future of Brain Mapping
Although the fruit fly’s connectome is a landmark achievement, it’s just the beginning. The techniques used to map the fly brain will be applied to larger, more complex brains in the future. Seung and his team have their sights set on the mouse brain. However, creating a connectome for larger species will require further advances in artificial intelligence and microscopy.
Dr. Seung emphasized the role AI will continue to play. “Mapping the whole brain has been made possible by advances in AI computing,” he explained.
Understanding how the neurons are connected is one thing; figuring out what that means for brain function is another. The researchers have already started using the fly connectome to simulate how the brain responds to stimuli. “Using our data, other scientists have already started trying to simulate how the fly brain responds to the outside world,” Dr. Gregory Jefferis, from the MRC Laboratory of Molecular Biology at the University of Cambridge, said in a press statement. “This is an important start, but we will need to collect many different kinds of data to produce reliable simulations.”
Toward Understanding Higher-Level Behaviors
The fly brain connectome is likely to have far-reaching implications for understanding higher-level behaviors like learning and memory—not just in flies, but in other species as well. Researchers are already studying how insects learn to avoid certain odors or use visual memories for navigation, and the connectome will provide a valuable tool for these efforts. Schlegel is particularly excited about the potential to study how a brain changes over time, such as when a fly learns to avoid a particular odor.
“One of the things I’d love to see in the future is a comparison between the naive FlyWire connectome and the connectome of a fly that has learned,” Schlegel said. With improvements in technology, such experiments may become routine.
Murthy’s lab is already using the connectome to study social behaviors in flies. These behaviors engage virtually every area of the brain, making the fly an ideal model for understanding how brains process information across different systems. “One important aspect of our connectome is its completeness—it contains all of the neurons of the fly brain, and one can follow information flow from sensory receptors all the way to motor outputs,” she said.
For now, the fruit fly’s brain offers an unprecedented look into the inner workings of a complete, functioning nervous system. As the connectome is studied in more detail, it promises to unlock even more secrets about how brains—from flies to maybe one day humans—process information, learn, and adapt.
With this work, the door is now open for a new era of brain research, where neuroscience and artificial intelligence merge to understand the fundamental mechanics of life’s most powerful and mysterious organ.
The new findings were revealed in a series of papers published in the journal Nature.
