Researchers have produced the first wiring diagram for the whole brain of a fruit fly, a feat that promises to revolutionise the field of neuroscience and pave the way for unprecedented insights into how the brain produces behaviour.
Rarely in science has so much effort been directed toward so little material, with scientists taking years to map the meanderings of all 139,255 neurons and the 50m connections bundled up inside 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 be asking 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 truly understand how any brain functions, it’s bound to tell us something about all brains.”
The intricate tangle of neurons, which if unravelled would reach for 150 metres, was mapped out through a painstaking process that started with slicing a female fruit fly brain into 7,000 thin slivers. Each section was imaged in an electron microscope to reveal structures as small as four-millionths of a millimetre wide.
The researchers then turned to artificial intelligence (AI) to analyse the millions of images and trace the path of every neuron and synaptic connection throughout the minuscule organ. Because the AI made plenty of mistakes, a global army of scientists and volunteers was recruited to help correct the errors and finalise the map.
The work has already borne fruit. Armed with the diagram, researchers have discovered “interrogator” neurons that appear to combine diverse types of information, and “broadcasters” that may send out signals to coordinate activity across different neural circuits. A specific neural circuit that, when triggered, causes fruit flies to stop in their tracks while walking, was also spotted.
In a foretaste of what is 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 can shed further light on how brain wiring gives rise to animal behaviour.
“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 in which 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, are published across 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 in five to 10 years. But repeating the feat for a whole human brain, with its 86bn neurons and trillions of connections, is another question. The human brain is roughly a million times more complex than the fruit fly brain, putting a complete wiring diagram beyond practical reach with today’s technology. It would also require some hefty memory: scientists estimate it would amount to a zettabyte of data, equivalent to all of 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 ultimately shed light on whether miswiring underpins neuropsychiatric and other brain disorders. “Simply put, we cannot fix what we do not understand and this is the basis of why we believe this is such an important moment today,” 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.”
