
Researchers at the Janelia Research Campus have unveiled the most comprehensive connectome of an adult fruit fly nerve cord to date. The connectome, constructed from approximately 23,000 neurons, 10 million pre-synaptic sites, and 74 million post-synaptic densities, provides an exceptional resource for the scientific community and reveals the intricate network controlling the fly’s motor functions. New insights have already emerged from the data, challenging previous theories on fly movement. For example, some behaviors involving the same muscles use distinct pre-motor microcircuits, contradicting existing theories. The unprecedented detail in this map of neurons and their connections will help scientists figure out how a fly moves its legs or flaps its wings, advancing understanding of fruit fly neurology and serving as a model for similar future projects.
The construction of the connectome was a joint effort by Janelia’s FlyEM Project Team and collaborators, and it is detailed in preprints on bioRxiv and is freely available to researchers worldwide. If the 23,000 neurons making up the connectome were laid end-to-end, they would stretch for about 44 meters. The connectome has already led to additional support for and interest in connectome efforts, with connectomes of the complete adult female fly brain and the optic lobe expected in 2023, and the complete male fly nervous system connectome following soon.
The connectome was constructed using methods akin to those used to map the hemibrain, with the Janelia team preparing the nerve cord sample and imaging layer after layer of nanometer-thick slices on focused ion beam scanning electron microscopes. Google’s algorithms and computers stitched the images together and did a first pass at identifying neurons. Then, a team of Janelians and collaborators set about proofreading the data – a manual effort to ensure that the shape and connectivity of neurons are correct, and one of the most time-consuming parts of the process. Researchers at Cambridge also identified the different cell types, where they are found along the fly’s body, and from which stem cells they originated, helping to tease out some of the organizational principles.
The connectome data has already started to uncover some surprises. For example, some behaviors involving the same muscles use distinct pre-motor microcircuits, not the same circuits, as previously thought. The complex repeated circuits that control the legs were also found to differ from existing models. Many more insights from the connectome are expected as other researchers start to probe the data, which can be accessed through neuPrint and Clio, online tools developed at Janelia.
Aside from the scientific insights to be gained, the project also serves as one model for other groups undertaking connectome efforts. “This kind of cooperation is going to be absolutely necessary when people start moving to the mouse connectome and things like that,” says Lou Scheffer, a principal scientist at Janelia and a member of the FlyEM team. “There’s no conceivable way any single organization could do it, and so this is a prototype for that sort of cooperation.”
- Fruit fly neuroscience
- Nerve cord mapping
- Connectomics
- Insect nervous system
- Neural circuitry
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