Complete Fruit Fly Brain ‘Connectome’ Advances Understanding of Essential Brain Functions in Health and Disease

Video credit: Tyler Sloan for FlyWire

You’ve surely seen fruit flies in your kitchen, perhaps hovering around a bowl of citrus fruits or over a glass of wine. While these insects might not seem especially brainy, typical fruit fly behaviors depend on a complex brain that’s wired to solve many of the same problems human brains do. Their nervous systems and brains must pick up on tempting scents and send the right signals through their bodies to move from one place to another to find food. Fruit flies form long-term memories, engage in social interactions with other fruit flies, and navigate over long distances. Though smaller than a poppy seed, the fruit fly brain is packed with hundreds of thousands of neurons and millions of neural connections all wired precisely to make those behavioral feats possible.

Now, a scientific team supported by the NIH Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®, has unveiled the first complete map, or connectome, of every neural connection within the brain of an adult female fruit fly. This important milestone in brain science, reported in nine papers in Nature , details more than 50 million connections between nearly 140,000 neurons. As the first complete map of a connectome of any adult animal, it offers critical information about how complex brains are wired to send and receive signals underlying normal brain functions.

To produce this map, the researchers relied on existing high-resolution microscopy scans of a fruit fly brain that had been cut into about 7,000 slices. This resulted in a collection of 21 million images representing more than 100 terabytes of data, equivalent to the storage of about 100 average laptop computers. They carefully annotated all the neurons, which represent more than 8,000 different cell types. With the help of artificial intelligence (AI) tools, the researchers used the data to develop a three-dimensional map. The FlyWire Consortium , a community of 287 researchers in more than 76 labs and volunteer citizen scientists, then “proofread” the map to check for errors.

Researchers around the world can now interact with the freely available fruit fly connectome data and access data analysis tools online to continue to make discoveries. The new 3D map can enable researchers to connect specific brain circuits and activities with certain fruit fly behaviors. Indeed, some of the studies in the paper package reported uses for the connectome in experimentally identifying or predicting neural circuits underlying specific functions or behaviors. The map is now a resource for exploring how nervous systems in general are put together and how they work.

While there’s still a lot to learn about how the human brain is wired and how it works, the fruit fly connectome serves as an important step toward developing the tools and capabilities required for mapping larger-brained animals and, eventually, the human brain, with its more than 80 billion neurons and 100 trillion connections. The connectome and the many exciting discoveries and developments yet to come will be critical for bringing much needed advances in understanding and one day treating a wide range of human brain disorders, including Alzheimer’s disease, Parkinson’s disease, severe depression, and addiction.

References:

Dorkenwald S, et al; FlyWire Consortium. Neuronal wiring diagram of an adult brain. Nature. DOI: 10.1038/s41586-024-07558-y (2024).

Schlegel P, et al. Whole-brain annotation and multi-connectome cell typing quantifies circuit stereotypy in Drosophila. Nature. DOI: 10.1038/s41586-024-07686-5 (2024).

NIH Support: National Institute of Mental Health, National Institute of Neurological Disorders and Stroke