Scientists have found 50 million reasons to study the brain of a fruit fly.
That鈥檚 how many connections they discovered in the first complete map鈥 known as a connectome鈥攐f an adult insect鈥檚 brain.
Although a fruit fly brain is only about the size of a poppy seed, it offers insights into how all brains perceive the world, make decisions and take action, says , a professor of neuroscience at Princeton University who helped lead the mapping effort.
鈥淭here鈥檚 a lot of fundamental principles of brain function that we can learn by studying the fly brain,鈥 says Murthy, who is also co-director of the project at Princeton.
The fly connectome also could help scientists begin to compare the brain wiring of different species, says , a senior group leader at the Howard Hughes Medical Institute鈥檚 Janelia Research Campus in Virginia who was not directly involved in the research.
鈥淚f we can understand what makes a bumblebee so much smarter than a fruit fly, that will tell us a lot about what makes a human so much smarter than a mouse,鈥 Rubin says.
The map and related research are featured in nine papers simultaneously in the journal Nature. These papers describe more than 8,000 cell types and look at how connections facilitate communication among brain regions.
Previously, scientists had created connectomes for the roundworm and a , which have much less sophisticated brains.
A little brain that does a lot
Adult fruit flies have intrigued brain scientists for decades because the animals鈥 small brains are capable of complex behaviors, like flying, fighting, and even flirting.
For example, when a male fruit fly sings a love song to a potential mate, he improvises, Murthy says.
鈥淗e chooses exactly what to sing based on feedback he gets from the female fly,鈥 she says, 鈥渁nd he patterns every note in accordance with her behavior.鈥
All that from a brain with only about 140,000 neurons. Humans, by comparison, have roughly 86 billion.
To understand how the neurons in a fruit fly do so much, you need to know how they鈥檙e connected, Murthy says.
鈥淚f you鈥檙e trying to figure out how the brain generates perceptions, thoughts, actions,鈥 she says, 鈥測ou really need to understand how information flows from sensory receptors all the way to the motor outputs of the brain.鈥
So Murthy and her colleague led an international team of scientists who set out to learn how a healthy brain鈥檚 wiring influences its function. Ultimately, they also hope to understand how 鈥渕iswiring鈥 leads to dysfunction in conditions ranging from epilepsy and autism, to schizophrenia and Alzheimer鈥檚.
The fruit fly brain was an obvious place to start.
Scientists had already found all of its neurons and knew a lot about the animal鈥檚 behavior. Then in 2018 scientists at the Janelia Research Campus a trove of more than 20 million electron microscope images of brain areas in a single female fruit fly.
The Princeton scientists thought they could assemble those images in a way that would reveal all the wiring between neurons. They got funding from the National Institutes of Health .
Artificial Intelligence with a human assist
The mapping process was a bit like filling in an enormous 3D coloring book, Seung says.
鈥淚f you want to trace out the wires of the brain, you鈥檝e got to color inside the lines,鈥 Seung says. 鈥淏ut that coloring book is so huge that it would take tens of thousands of years for a single person to color it all in.鈥
The team used computers and artificial intelligence to speed things up. Even so, the process took years, and the brain map it produced still had flaws.
鈥淪o a team of human experts, people who are trained to do this, they had to go in and correct the errors of the artificial intelligence,鈥 Seung says.
That took more years of work by hundreds of scientists around the globe. Ultimately, though, the effort produced an accurate, annotated map of all 50 million connections in a fruit fly brain.
The research also includes a description of each neuron and information about which chemical neurotransmitters it produces. This lets scientists know things like whether a given neuron is amplifying the messages it receives or inhibiting them 鈥 information is critical to understanding both healthy brain circuits and those affected by certain brain disorders.
The new papers are an important step for the field, Rubin says. 鈥淏ut it鈥檚 not like we now have it and we鈥檙e done.鈥
Scientists still need to learn how connectomes differ from fly to fly, and how behavior is influenced by brain cells that are not neurons, and therefore not part of the connectome.
The project will truly be finished when scientists fully understand 鈥渉ow this little brain controls the behavior of a fly in all its wondrous navigating in space and finding a mate and fighting off competitors,鈥 Rubin says.
Even so, researchers are already hard at work on a connectome of a mouse brain, which has about 1,000 times more neurons than the brain of a fruit fly.
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