An international team of scientists and citizen scientists has just completed a herculean task: creating a complete map – called a connectome – of the entire fruit fly brain.
It’s not only a scientific breakthrough, but a project – unveiled a few hours ago – that could produce major improvements in understanding how other brains work, with implications for the understanding and treatment of mental illness and addiction in humans.
Fruit flies, those short-lived insects beloved by generations of geneticists and biology students, are tiny. But they are capable of remarkably complex behaviours, says Princeton University neuroscientist Mala Murthy, codirector of the FlyWire Consortium, which coordinated the project. They can walk, fly, find food, learn, remember, and interact socially. All with a brain the size of a poppy seed.
That tiny brain, the scientists reported in a suite of papers in this week’s issue of Nature, proved to have 140,000 neurons, 54 million synapses, and 149 meters of neuronal “wiring.”
Mapping was an extremely complex process which began by slicing the brain into 7,000 microscopically thin sections, each of which was then scanned at 4-nanometer precision under a powerful microscope, says Sven Dorkenwald of the University of Washington’s Allen Institute,
And that was the easy part. The next step was to combine all of these cross-sections into a 3D image in which not only the neurons, but their interconnections could be traced.
To do that, the scientists created it with an AI trained to do it as precisely as possible. But there was no way the AI would be fully accurate, so they then put the initial results online where a large team of people, including citizen scientists, could scour the data, looking for errors.
All told, says Gregory Jefferis of the University of Cambridge, UK, these helpers eventually found and corrected over 600,000 errors—a process that John Ngai, head of the Brain Research Through Advanced Innovative Neurotechnologies program at the U.S. National Institutes of Health, says took a total of 33 person-years to complete.
Even that was just the first step. Jefferis compares it to having satellite images on which you can see streets and buildings, but don’t know exactly what they are. The next step, he says, “could be likened to putting names on streets and towns, putting in the business opening times, phone numbers, etc. You need both the base map and these annotations to make it really useful.”
So far, that has been most easily accomplished with vision. “The eye of the fly is like a pixel map,” Murthy says. “By looking at the connectivity downstream of that pixel map you can infer what the functions might be like in other parts of the brain.” Other researchers, she says, have studied the olfactory system and the circuits involved in walking, and have found “hub neurons” that appear to speed up the flow of information though the brain. There is also work, Jefferis says, to predict what neurotransmitters are most likely produced at each of the interconnections, thereby determining if these connections allow an incoming nerve transmission to continue, or block it.
Next up, the scientists say, is the mouse brain (1000 times more complex than the fruit fly brain), followed someday by the human brain (1000 times more complex than the mouse).
Read more: It’s just not fruit fly brain they’re peering into
Ultimately, the goal is to understand not only how the brain works, but how it goes awry in mental illness or addiction. “Right now, we’re limited to treatments that only help people along but don’t really cure them from their afflictions,” Ngai says. “Simply put, we cannot fix what we do not yet understand.”
Getting a full map of the human brain might take a while—but we may start to see benefits much sooner than that, Murthy says, noting that addiction is based on reward pathways in the brain, “[and] there are reward pathways in the brains of fruit flies.” These, she says, “can now be studied at the connectome level to really understand how the circuitry of the fly gives rise to behaviors related to rewards.”
“The key,” Ngai adds, “is to understand what the commonalities are, what the differences are.”
Also, he notes, there’s long been speculation that at least one mental illness, schizophrenia, is caused by miswiring of the brain. “The general public,” he says, “will say, ‘Oh yeah, John is just that way. He’s wired differently.’ But it’s not science yet, because we’ve never been able to see the wiring.” But hopefully, he says, the technology used to map the fruit fly brain will continue to advance to the point where that can be done. “I think it has huge potential, and people are actively excited to be looking at these kinds of issues
