Researchers have produced the first wiring diagram for the entire brain of a fruit fly, an achievement that promises to revolutionize the field of neuroscience and pave the way for unprecedented insights into how the brain produces behavior.
Rarely in science has so much effort been directed at so little material, with scientists taking years to map the windings of all 139,255 neurons and the 50m connections strung together in the fly’s poppy seed-sized brain.
In the process, the researchers classified more than 8,400 different cell types, amounting to the first complete parts list for building a fly brain.
“You might ask why we should care about the brain of a fruit fly,” says Sebastian Seung, a professor of computer science and neuroscience at Princeton University and a co-leader on the FlyWire Project. “My simple answer is that if we can truly understand how any brain functions, it will certainly tell us something about all brains.”
The intricate tangle of neurons, which if unraveled would stretch up to 150 meters, was mapped out by a painstaking process that began with cutting a female fruit fly brain into 7,000 thin slices. Each section was imaged in an electron microscope to reveal structures as small as four-millionths of a millimeter wide.
The researchers then turned to artificial intelligence (AI) to analyze the millions of images and trace the path of each neuron and synaptic connection through the tiny organ. Because the AI made many mistakes, a worldwide army of scientists and volunteers was recruited to help correct the mistakes and finalize the map.
The work has already paid off. Armed with the diagram, researchers discovered “interrogator” neurons that appear to combine different types of information, and “broadcasters” that can send out signals to coordinate activity across different neural circuits. A specific neural circuit that, when activated, causes fruit flies to stop in their tracks while walking has also been noted.
In a taste of what’s to come, researchers used the wiring diagram, known as the connectome, to build a computer simulation of part of the fly brain. Experiments with the simulation led them to identify neural circuits used to process taste, suggesting that future simulations may shed further light on how brain wiring gives rise to animal behavior.
“Connectomics is the beginning of a digital transformation of neuroscience … and this transformation will extend to brain simulation,” Seung said. “This is going to be a rapid acceleration of the way we do neuroscience.”
Details of the project, which involved researchers from Canada, Germany and the MRC Laboratory for Molecular Biology and the University of Cambridge in the UK, are being published around the world. nine papers in nature. In an accompanying article, Dr. Anita Devineni, a neuroscientist at Emory University in Atlanta, called the wiring diagram a “landmark achievement.”
Work has already begun to produce a complete wiring diagram for the mouse brain, which researchers hope to complete within five to 10 years. But replicating the feat for an entire human brain, with its 86 billion neurons and trillions of connections, is another question. The human brain is about a million times more complex than the fruit fly brain, which puts a complete wiring diagram out of practical reach with today’s technology. It will also require massive amounts of memory: scientists estimate it will amount to a zettabyte of data, equivalent to all the world’s internet traffic for a year.
A more realistic approach is to map neuronal wiring in parts of the human brain, research that could eventually shed light on whether miswiring underpins neuropsychiatric and other brain disorders. “Simply put, we can’t fix what we don’t understand and that’s the basis for why we believe today is such an important moment,” said Dr. John Ngai, the director of the US National Institutes of Health’s Brain Initiative .
“We clearly have a big task ahead of us.”
