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 such a small material, with scientists taking years to map the windings of all 139,255 neurons and 50 meters of connections packed inside a fly’s brain the size of a poppy seed.
In the process, the researchers classified more than 8,400 different types of cells, arriving at the first complete list of the building blocks of a fly’s brain.
“You might ask why we should care about the brain of a fruit fly,” said 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 really understand how each brain works, it will tell us something about the whole brain.”
The intricate release of neurons, which if unfurled would reach 150 meters, was mapped through a painstaking process that began with slicing the brain of a female fly into 7,000 thin pieces. Each section was photographed in an electron microscope to reveal structures as small as four millionths of a millimeter across.
The researchers then turned to artificial intelligence (AI) to analyze millions of images and trace the path of each neuron and synaptic connection throughout the tiny organ. Because the AI made so many mistakes, a global army of scientists and volunteers was recruited to help correct the errors and finalize the map.
The work has already paid off. Armed with the diagram, the researchers discovered “investigator” neurons that appear to combine different types of information and “transmitter” neurons that can send 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 was also observed.
In a preview of what’s to come, the researchers used the connection diagram, known as a connectome, to build a computer simulation of part of a fly’s brain. Experiments with the simulation led them to identify the neural circuits used to process taste, suggesting that future simulations may shed more light on how the brain’s wiring causes animal behavior.
“Connectomics is the beginning of a digital transformation of neuroscience … and this transformation will extend to brain simulation,” Seung said. “This will be a rapid acceleration of the way we do neuroscience.”
Details of the project, which involved researchers from Canada, Germany and the MRC Laboratory of Molecular Biology and the University of Cambridge in the UK, have been published in nine papers in Nature. In an accompanying article, Dr Anita Devineni, a neuroscientist at Emory University in Atlanta, called the connection diagram a “landmark”.
Work has already begun to produce a complete wiring diagram for the mouse brain, which the researchers hope to complete in five to 10 years. But replicating the success for an entire human brain, with its 86 billion neurons and trillions of connections, is another question. The human brain is roughly a million times more complex than the brain of a fruit fly, putting a complete diagram of the connections beyond practical possibilities with today’s technology. It would also require a strong memory: scientists estimate that it would 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 connections in parts of the human brain, research that could eventually shed light on whether faulty connections underlie neuropsychiatric and other brain disorders. “Simply put, we can’t fix what we don’t understand, and that’s the basis of why we believe this is such an important moment today,” said Dr. John Ngai, director of the National Institutes of Health’s Brain Initiative. USA.
“It is clear that we have a big task ahead of us.