Scientists have created the first complete brain-to-body wiring map of a fruit fly, revealing that complex behavior may arise from distributed neural teamwork rather than a central controller.
A large international research team led by labs at Harvard Medical School and Princeton University has reached a major neuroscience milestone: a complete wiring diagram of every connection between neurons in the central nervous system of an adult fruit fly.
The achievement gives scientists a new way to study how the brain and body work together to produce complex behaviors, including walking and flying. It also opens the door to deeper questions about the basic rules that govern nervous systems.
“We can see all of the neurons and their connections as a complete unit for the first time and ask, ‘What do we learn from that?’” said study co-senior author Rachel Wilson, the Joseph B. Martin Professor of Basic Research in the Field of Neurobiology in the Blavatnik Institute at HMS.
First Complete Fruit Fly Nervous System Map
The detailed map of neural connections, called a connectome, adds the fruit fly’s version of a spinal cord, known as the nerve cord, to an earlier connectome of the fly brain.
“It is really important to have a central nervous system connectome that is as complete as possible so we can link up the brain and body and start thinking about behavior holistically,” said study co-senior author Wei-Chung Allen Lee, associate professor of neurobiology at HMS and HMS professor of neurology at Boston Children’s Hospital.
When the researchers analyzed the connectome, they found that many fruit fly behaviors are not directed by a single command center in the brain. Instead, they are often controlled by local neural circuits in the body parts involved in the action.
The full connectome is freely available online, giving scientists around the world a new resource for advancing neuroscience research. The study was published on June 8 in Nature and received support in part from U.S. federal funding, including the BRAIN Initiative (Brain Research Through Advancing Innovative Neurotechnologies), the National Institutes of Health, and the National Science Foundation.
Why Fruit Flies Matter in Neuroscience
One of neuroscience’s major unanswered questions is how neurons in the brain and body connect and cooperate to create behavior. The fruit fly Drosophila melanogaster is a powerful model for studying that problem.
Fruit flies are easy to breed and care for in the laboratory. Their nervous systems are relatively simple, with about 160,000 neurons, yet they can perform complex behaviors such as navigation, social interaction, learning, and responses to sensory cues. They also offer what Lee calls an incredibly sophisticated genetic toolkit, allowing researchers to access, control, and record activity from single neurons or groups of neurons.
In 2024, the FlyWire Consortium, led by Mala Murthy and Sebastian Seung at Princeton, who are also co-authors of the new study, published a complete connectome of a fruit fly brain. At the same time, Lee and his colleagues were building a connectome of the fruit fly nerve cord, which controls the legs, wings, and other appendages while also processing sensory information.
“The brain and nerve cord connectomes are each useful on their own, but until you can bridge the two, it’s hard to understand how information moves between the brain and the body,” said co-first author Helen Yang, a research fellow in neurobiology in the Wilson Lab.
Co-first author Alexander Bates, also a research fellow in neurobiology in the Wilson Lab, noted that although most of the neurons are in the brain, the neurons in the nerve cord are “some of the most useful” because they are tied to functions such as sensation and movement and are easier to interpret.
Linking the Brain and Body
Murthy, the Karol and Marnie Marcin ’96 Professor of Neuroscience at Princeton and director of the Princeton Neuroscience Institute (PNI), said the FlyWire team was eager to shift its focus to the brain and neural cord, or BANC, dataset imaged in the Lee Lab.
“The new connectome represents a major advance for the field, with the ability to understand how circuits in the brain receive feedback from and control the actions of the body,” she said.
“For the first time, we can follow information flow from sensation to action across an entire nervous system,” added co-author Arie Matsliah of the PNI.
Building a 3D Connectome
To create the connectome, the researchers prepared thousands of thin serial sections from a single fruit fly. They imaged those sections with electron microscopy, generating millions of images that captured neurons and their connections. AI tools were then used to line up the images and assemble them into a unified 3D map.
The finished connectome shows, at the synapse level, how each neuron connects with other neurons in the brain and nerve cord. Although it does not cover the fly’s entire body, the researchers used identifiable neurons and previous scientific literature to link central nervous system neurons to many appendages and sensory organs. In doing so, they effectively “embodied” the connectome.
Lee said researchers can now use the connectome to generate new hypotheses that can be tested in the lab. He compares the resource to using the detailed information in Google Maps to plan a route.
“The connectome has shown us that most of our hypotheses are too simple. Now, we can develop more complex hypotheses and move forward with experiments to test them,” Lee said.
A Surprise in Motor Control
The authors have already used the connectome to investigate motor control, including how a fruit fly moves its legs and other body parts.
A long-standing idea in neuroscience is that the brain acts as a centralized controller, making decisions about which actions an animal will take.
That was not what the team found.
Instead, the researchers discovered that motor control in the fruit fly is largely organized locally. For instance, the movement of one leg is mainly controlled by the neural circuits associated with that leg. Those local circuits then communicate with circuits for other legs to produce coordinated movements such as walking.
The same pattern appeared in circuits for the wings, mouth, and other body parts. The researchers also found that motor circuits connect with other kinds of circuits, including those in the visual and endocrine systems, which supply additional information that helps shape behavior.
“Our findings suggest that control for actions is highly distributed in local modules that link up and work together in different ways,” Bates said.
What Comes Next
The researchers expect the connectome to support many future studies. Yang compares it to the Human Genome Project, another major open resource that has enabled a wide range of scientific advances.
In the near future, the team plans to expand the connectome by adding more information, including details about neuropeptides, the small protein-like molecules that neurons use to communicate.
The connectome could also help reveal core principles of how nervous systems work across species, including in humans. Bates said many discoveries in fruit flies have carried over from invertebrates to mammals, including findings related to navigation, olfaction, and memory.
Another goal is “to bring full-connectome mapping to much more complex organisms,” said Matsliah. He said advances in AI, computation, and open collaborative science are making that kind of work increasingly possible.
One major question is whether the distributed control of neural circuits seen in fruit flies is also found in other animals. Lee is now studying that question in mice.
“I would be shocked if this is unique to the fly,” Yang said. “We don’t have this level of resolution in other animals, but we know that they have a lot of these local circuits.”
Fruit Fly Connectome and AI
The work may also have implications for artificial intelligence. The connectome offers concrete biological data that could help guide the design of artificial agents that move through virtual worlds, which are increasingly used to study intelligence and improve AI training.
“One thing that always amazes me is that this tiny little fly does a hell of a lot; even our best AI agents and robots can’t do everything that a fly does,” Yang said. “There may be lessons for AI in how the nervous system is organized.”
Reference: “Distributed control circuits across a brain-and-cord connectome” by Alexander S. Bates, Jasper S. Phelps, Minsu Kim, Helen H. Yang, Arie Matsliah, Zaki Ajabi, Eric Perlman, Kevin M. Delgado, Mohammed Abdal Monium Osman, Christopher K. Salmon, Jay Gager, Benjamin Silverman, Sophia Renauld, Farzaan Salman, Janki Patel, Matthew F. Collie, Jingxuan Fan, Diego A. Pacheco, Yunzhi Zhao, Wenyi Zhang, Laia Serratosa Capdevila, Ruairí J. V. Roberts, Eva J. Munnelly, Nina Griggs, Helen Langley, Borja Moya-Llamas, Zuoyu Zhang, Ryan T. Maloney, Szi-chieh Yu, Amy R. Sterling, Marissa Sorek, Krzysztof Kruk, Nikitas Serafetinidis, Serene Dhawan, Finja Klemm, Paul Brooks, Ellen Lesser, Jessica M. Jones, Sara E. Pierce-Lundgren, Su-Yee Lee, Yichen Luo, Andrew P. Cook, Theresa H. McKim, Dimitrios Stasi Giakoumas, Benjamin Gorko, Justin Ellis-Joyce, Jiayi Zhang, Emily C. Kophs, Tjalda Falt, Alexa M. Negron-Morales, Austin Burke, James Hebditch, Kyle P. Willie, Ryan Willie, Sergiy Popovych, Nico Kemnitz, Dodam Ih, Kisuk Lee, Ran Lu, Akhilesh Halageri, J. Alexander Bae, Ben Jourdan, Gregory Schwartzman, Damian D. Demarest, Emily Behnke, Doug Bland, Anne Kristiansen, Jaime Skelton, Tom Stocks, Dustin Garner, Anthony Hernandez, Sandeep Kumar, The BANC-FlyWire Consortium, Kevin C. Daly, Sven Dorkenwald, Forrest Collman, Marie P. Suver, Lisa M. Fenk, Michael J. Pankratz, Zepeng Yao, Fei Wang, Stephen J. Huston, Tomke Stürner, Gregory S. X. E. Jefferis, Katharina Eichler, Andrew M. Seeds, Stefanie Hampel, Sweta Agrawal, Tatsuo S. Okubo, Meet Zandawala, Thomas Macrina, Diane-Yayra Adjavon, Jan Funke, John C. Tuthill, Anthony Azevedo, H. Sebastian Seung, Benjamin L. de Bivort, Mala Murthy, Jan Drugowitsch, Rachel I. Wilson and Wei-Chung Allen Lee, 8 June 2026, Nature.
DOI: 10.1038/s41586-026-10735-w
Funding was provided by the National Institutes of Health (grants R01NS121874; RF1MH117808; U19NS118246; U24NS126935; RF1MH117815; K99NS129759; R00NS117657; R01NS102333; RF1NS128785; R01NS140174; UM1NS132253; U24NS13992; RF1MH128840; R01NS121911; T32GM144273; R01DK139131; R25NS080687), a Sir Henry Wellcome Postdoctoral Fellowship (222782/Z/21/Z), a Smith Family Foundation Odyssey Award, a Harvard/MIT Joint Research Grant, an HHMI Life Sciences Research Foundation Postdoctoral Fellowship (PJ100000343), a New York Stem Cell Foundation Robertson Neuroscience Investigator Award, the Deutsche Forschungsgemeinschaft (ZA1296/1-1; EXC2151-390873048; PA787/7-3; PA787/9-3), the Nevada IDeA Network of Biomedical Research Excellence (GM103440), the National Science Foundation (2127379; 2014862), the Japan Society for the Promotion of Science (KAKENHI 25K00370), the Japan Science and Technology Agency (ASPIRE JPMJAP2302; CRONOS JPMJCS24K2), an HHMI Gilliam Fellowship (GT15790), the Max Planck Society, the Shanahan Family Foundation, a Kempner Graduate Fellowship, the Medical Research Council (MC_EX_MR/T046279/1), the Alice and Joseph Brooks Fund, and the Beijing Natural Science Foundation (IS23084). The authors also acknowledge that the work benefited from the O2 High-Performance Compute Cluster, supported by the Research Computing Group at HMS.
Harvard University filed a patent application for GridTape (WO2017184621A1) on behalf of the inventors, including W. Lee, and negotiated licensing agreements with interested partners. Macrina, Popovych, Kemnitz, Ih, K. Lee, Lu, Halageri, Bae, and Seung declare financial interest in Zetta AI. Seung declares financial interest in Memazing, Inc. Capdevila, Roberts, Langley, Munnelly, Griggs, and Moya-Llamas declare financial interest in Aelysia Ltd. Perlman is a principal of Yikes LLC.
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