They publish the first complete atlas of the fly brain, a Google Maps of neural connections.

At least the brain of a fruit fly(Drosophila melanogaster) is less than a millimeter wide, the publication of the first complete map of its neural connections is a giant leap for neuroscience. Scientists at the FlyWire Consortium cut this tiny brain into approximately seven thousand 40-nanometer-thick slices and used a high-resolution electron microscope to map the 54.5 million connections of its 139,255 neurons.

The results are published this Wednesday in a group of nine papers in the journal. Nature which describe the most ambitious step to date in the Human Connectome Project, which aims to map highway neurons to understand how they produce complex behavior.

The largest fruit fly connectome so far comes from a “brain hemisphere” that contains only about 20,000 neurons, and much smaller brains have also been studied, such as those of the fruit fly larva, which has 3,016 neurons, and the fruit fly. nematode worm K. elegansin which there are only 302 neurons.

The researchers believe this is a key first step toward creating larger brains and improving our understanding of how neural circuits work. Because although the brains Drosophila With about a million times fewer neurons than the human brain, fruit flies exhibit a range of complex behaviors, from flight and navigation to social interactions.

Neural Google Maps

“This data set is a bit like Google Mapsbut for the brain,” explains Philipp Schlegel, first author of one of the studies and a researcher at the MRC Laboratory of Molecular Biology. “What we’ve created is in many ways an atlas,” adds Sven Dorkenwald, lead author of the magazine’s star article Nature. “Just like you wouldn’t want to go to a new place without Google Mapsyou don’t want to explore the brain without a map. What we did was create a brain atlas and add annotations for all the businesses, buildings, and street names. Thanks to this, researchers can now thoughtfully navigate the brain as we try to understand it.”

Just like you wouldn’t want to drive to a new place without Google Maps, you wouldn’t want to explore your brain without a map.

Sven Dorkenwald
— Lead author of the most famous paper on the volatile connectome.

According to the authors, the work allows us to study how the structure of brain circuits determines brain function, which is a valuable resource for neuroscience research. In addition, the methods used to construct the electrical circuitry of the fruit fly brain lay the groundwork for future large-scale connectome projects in other species, including mammals such as mice, which are the next target.

“Mapping the entire brain has been made possible by advances in artificial intelligence computing,” emphasizes Sebastian Seung, a researcher at Princeton University and one of the study leaders. “It would be impossible to manually restore the entire connection diagram. This is an example of how AI can advance neuroscience. “The fly brain is a milestone on our path to reconstructing the electrical circuitry of the entire mouse brain.”

A Key Step to Understanding the Brain

The project involved managing more than 100 terabytes of image data, and although the map was developed by the FlyWire consortium based at Princeton University, it is the result of a collective effort between teams from more than 76 laboratories with 287 researchers from around the world. world. The study was conducted using the brain of a female fly. Because there are differences in the neuronal structure of the brains of male and female flies, the researchers plan to characterize the brains of males in the future as well.

“If we want to understand how the brain works, we need a mechanistic understanding of how all the neurons connect to each other and allow us to think,” says Gregory Jefferies, one of the study’s co-principal investigators. “Most brains have no idea how these networks work. “Without a detailed understanding of how neurons connect to each other, we will not have a basic understanding of what goes right in a healthy brain or what goes wrong in disease,” said John Ngai, director of the BRAIN Initiative at NUS. Health institutions that provided partial funding for the FlyWire project.

We hope that in the future it will be possible to compare what happens when something goes wrong in our brain, such as in mental disorders.

Mala Murthy
— Princeton University researcher, study co-principal investigator

“We hope this will change the work of neuroscientists trying to better understand how the healthy brain works,” concludes Mala Murthy, a researcher at Princeton University and co-principal investigator of the study. “We hope that in the future it will be possible to compare what happens when something goes wrong in our brain, such as in mental disorders.”

“Titanic Effort”

Juan Lerma, a researcher at the Institute of Neurosciences of Alicante, highlights the “herculean effort” required to map the connections Drosophila and the importance of the computational algorithms being developed. “The authors took into account the previous description of the half-brain (hemisphere of the brain) and found no large differences, indicating that the variability between individuals is small and therefore these very detailed data can be generalized to the fly brain. rage“, he explains to elDiario.es. For Lerma, having this highly accurate connectome map, which is also publicly available, “marks the first step in modeling this brain to answer important questions, especially around sensory integration, which is where much of this brain is devoted.”

These findings open new avenues for studying the mechanisms underlying cognition, behavior, and neurological disorders.

Javier de Felipe
— Neuroscientist at the Cajal Institute-CSIC

Spanish neuroscientist Javier de Felipe of the Cajal Institute-CSIC believes that having a complete connectome allows structure to be correlated with function, offering a basis for studying how genetic or molecular modifications affect the brain and behavior. In his opinion, technological advances that allow large-scale brain reconstructions using electron microscopy represent a real revolution in neuroscience. “They offer an unprecedented level of detail in the structure and connections of the brain, which opens up new opportunities for studying the mechanisms underlying cognition, behavior and neurological disorders,” he emphasizes. ”

Javier Morante Oria, a senior scientist at CSIC, believes that obtaining a complete connectome is a big leap, and remembers that although the fly is a model mechanism and a tiny insect, it has complex behavior. “These are simpler organisms, but they perform the same functions as us; They eat, they reproduce and they sleep,” he says. “This is a way to learn the basic and general principles, understand how neurons connect, and this can be used for clinical applications in the future.”

Sergio Casas Tinto is a researcher at the Carlos III Institute of Health (ISCIII) dedicated to health research. Drosophilabelieves that this work sets a crucial precedent for studying the brains of other animals, including vertebrates and humans. “This technology will enable detailed analysis of synaptic connections, which will change the diagnosis and treatment of neurodegenerative diseases and mental disorders such as Alzheimer’s disease, Parkinson’s disease, brain tumors, schizophrenia or depression,” he says. Of course, he cautions, differences between the brains of flies and those of other organisms, such as mammals, necessitate further research. “And future work should take into account variability between individuals or between sexes, which may be relevant in studies of neurodiversity or functional specialization.”