Fruit flies are capable of sophisticated behaviors, including navigating diverse landscapes, tussling with rivals and serenading potential mates. And their speck-size brains are tremendously complex, containing some 100,000 neurons and tens of millions of connections, or synapses, between them.

Since 2014, a team of scientists at Janelia, in collaboration with researchers at Google, have been mapping these neurons and synapses in an effort to create a comprehensive wiring diagram, also known as a connectome, of the fruit fly brain.

The work, which is continuing, is time-consuming and expensive, even with the help of state-of-the-art machine-learning algorithms. But the data they have released so far is stunning in its detail, composing an atlas of tens of thousands of gnarled neurons in many crucial areas of the fly brain.

By analyzing the connectome of just a small part of the fly brain—the central complex, which plays an important role in navigation—Dr. Jayaraman and his colleagues identified dozens of new neuron types and pinpointed neural circuits that appear to help flies make their way through the world. The work could ultimately help provide insight into how all kinds of animal brains, including our own, process a flood of sensory information and translate it into appropriate action.

It is also a proof of principle for the young field of modern connectomics, which was built on the promise that constructing detailed diagrams of the brain’s wiring would pay scientific dividends. “It’s really extraordinary”, Dr. Clay Reid, a senior investigator at the Allen Institute for Brain Science in Seattle, said of the new paper. “I think anyone who looks at it will say connectomics is a tool that we need in neuroscience—full stop.”

…Several teams at Janelia have embarked on fly connectome projects in the years since, but the work that led to the new paper began in 2014, with the brain of a single, 5-day-old female fruit fly. Researchers cut the fly brain into slabs and then used a technique known as focused-ion beam scanning electron microscopy to image them, layer by painstaking layer. The microscope essentially functioned like a very tiny, very precise nail file, filing away an exceedingly thin layer of the brain, snapping a picture of the exposed tissue and then repeating the process until nothing remained…The team then used computer vision software to stitch the millions of resulting images back together into a single, 3-dimensional volume and sent it off to Google. There, researchers used advanced machine-learning algorithms to identify each individual neuron and trace its twisting branches. Finally, the Janelia team used additional computational tools to pinpoint the synapses, and human researchers proofread the computers’ work, correcting errors and refining the wiring diagrams.

…Last year, the researchers published the connectome for what they called the “hemibrain”, a large portion of the central fly brain, which includes regions and structures that are crucial for sleep, learning and navigation.

The connectome, which is accessible free online, includes about 25,000 neurons and 20 million synapses, far more than the C. elegans connectome. “It’s a dramatic scaling up”, said Cori Bargmann, a neuroscientist at the Rockefeller University in New York. “This is a tremendous step toward the goal of working out the connectivity of the brain.”

…For instance, Hannah Haberkern, a postdoctoral associate in Dr. Jayaraman’s lab, analyzed the neurons that send sensory information to the ellipsoid body, a doughnut-shape structure that acts as the fly’s internal compass. Dr. Haberkern found that neurons that are known to transmit information about the polarization of light—a global environmental cue that many animals use for navigation—made more connections to the compass neurons than did neurons that transmit information about other visual features and landmarks.

…Other members of the research team identified specific neural pathways that seem well suited to helping the fly keep track of its head and body orientation, anticipate its future orientation and traveling direction, calculate its current orientation relative to another desired location and then move in that direction.

…Creating connectomes of larger, more complex brains will be enormously challenging. The mouse brain contains roughly 70 million neurons, the human brain a whopping 86 billion. But the central complex paper is decidedly not a one-off; detailed studies of regional mouse and human connectomes are currently in the pipeline, Dr. Reid said: “There’s a lot more to come.” Journal editors, consider yourselves warned.

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