Brain research is making constant progress and yet many processes in our thinking organ remain a mystery. Neuroscientists have now achieved a breakthrough: They have created a map that allows the functioning of the brain to be examined in greater detail than was previously possible. It is the first circuit diagram of an entire brain of an animal that can move and see – that of the fruit fly. The map includes around 140,000 neurons and over 50 million neural connections. In the future, the brains of other species could also be mapped, as the team reports in “Nature”.
Our brain controls how we behave. This is made possible by the numerous neurons in the brain, which are connected and interconnected in a complex way. Therefore, to understand how the brain works, one must understand the connections between brain cells. Researchers have long been trying to create a neural map that details these circuits.
Drosophila as a model
Neuroscientists use the fruit fly (Drosophila melanogaster) as a starting point. The fly brain contains about a million times fewer neurons than the human brain. However, the fruit fly already displays a range of complex behaviors, from flying and navigation to social interactions. In addition, 60 percent of human DNA is identical to that of fruit flies and three out of four genetic diseases in humans also occur in fruit flies. The animals are therefore predestined as model organisms. However, so far it has only been possible to create incomplete maps of the fly brain.
A research team from the “FlyWire Consortium” led by Sven Dorkenwald from Princeton University has now created a complete map for the entire brain for the first time. To do this, the researchers cut the tiny brain of a female fruit fly into 7,000 thin slices and took high-resolution images using electron microscopes. The team of neuroscientists and professional tracers then used these 21 million images to meticulously map the positions and connections of each individual brain cell. With the help of AI, this mountain of data was turned into a 3D map, which the scientists carefully examined.
Complete wiring diagram of the fly brain
The finished circuit diagram, also known as the connectome, now shows all 139,255 neurons and 54.5 million synapses of the fly. That’s around seven times more neurons and almost four times more switching points than the brain map, which was previously considered the most comprehensive. “This is a great success,” says senior author Mala Murthy from Princeton University. “There is no other complete brain connectome for an adult animal of this complexity.” In a second step, the neuroscientists also labeled this brain map and added detailed notes about the individual cells and circuits. The fly brain therefore contains more than 8,400 different cell types, 4,581 of which were previously unknown. These are located in brain regions that were not shown on previous maps.
In addition, the researchers also examined which synapses and neuronal circuits are responsible for certain behaviors or movements. For example, they found three neurons that cause flies to pause in their movements: called Foxglove, Bluebell and Brake. This shows more clearly than ever before how the body and brain communicate with each other and how the structure of the brain determines its function. When comparing the new map with previous partial maps of the fly brain, the scientists also found considerable similarities in terms of the wiring of the brain cells. Only 0.5 percent of the neurons were connected differently. The team concludes that individual brains are structured very similarly and are not unique like a snowflake. Follow-up studies must now show whether the 0.5 percent change is an expression of individuality or brain disorders.
Flies Sing: Male flies use their wings to hum various tunes that will land them a mate. Female flies use this tune to decide whether to mate with a male. These brain cells are responsible for recognizing songs and play a role in decision making. © Amy Sterling, Murthy and Seung labs, Princeton University, (Baker et al., Current Biology, 2022)
Google Maps for the brain
“What we have built is in many ways an atlas, a kind of Google Maps for the brain,” says Dorkenwald. “This means researchers are now able to carefully explore the brain while trying to understand it.” Co-author Gregory Jefferis from the University of Cambridge adds: “The brain’s wiring diagrams are a first step towards understanding all that what interests us – how we control our movements, answer the phone or recognize a friend.”
Using the techniques used to construct the circuit diagram of the fruit fly brain, the brains of other species could also be mapped in the future, the researchers report. The study paves the way for the complete mapping of larger brains, including that of humans. The development could one day lead to tailored treatments for brain diseases and mental illnesses. The next milestones, however, are to map the brains of male fruit flies and mice.
Sources: Sven Dorkenwald (Princeton University) et al.; Nature, doi: 10.1038/s41586-024-07558-y. Philipp Schlegel (MRC Laboratory of Molecular Biology) et al.; Nature, doi: 10.1038/s41586-024-07686-5. Further studies of the FlyWire Consortiums.