Although the brain of a fruit fly (Drosophila melanogaster) is less than a millimeter wide, the publication of the first complete map of its neuronal connections represents a giant step forward for neuroscience. FlyWire Consortium scientists cut this tiny brain into approximately seven thousand 40-nanometer-thick slices and, using a high-resolution electron microscope, mapped the 54.5 million connections of its 139,255 neurons .
The results are published this Wednesday in a group of nine articles in the journal Nature which describe the most ambitious step yet in the Human Connectome project, which aims to map highways neurons to understand how they give rise to complex behaviors.
The largest fruit fly connectome so far came from a “hemicebrain,” which contained only about 20,000 neurons, and much smaller brains had been studied, such as that of a fruit fly larva. fruit, which has 3,016 neurons, and that of the fruit fly. nematode worm C. eleganswhich only has 302 neurons.
Researchers believe this is a key first step toward achieving larger brains and advancing our understanding of how neural circuits work. Because, even if the brain of Drosophila Having about a million times fewer neurons than the human brain, fruit flies exhibit a range of complex behaviors, from flight to navigation to social interactions.
A neural “Google Maps”
“This dataset is a bit like Google Mapsbut for the brain,” explains Philipp Schlegel, first author of one of the studies, researcher at the MRC molecular biology laboratory. “What we have built is, in many ways, an atlas,” adds Sven Dorkenwald, lead author of the featured paper in Nature. “Just like you wouldn’t want to drive to a new place without Google Mapsyou wouldn’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. With this, researchers are now equipped to thoughtfully navigate the brain as we try to understand it.
Just like you wouldn’t want to go somewhere new without Google Maps, you wouldn’t want to explore the brain without a map.
Sven Dorkenwald
— Lead author of the most notable paper on the on-the-fly connectome
Together, the authors say, this work allows us to study how the structure of brain circuits determines how the brain functions, providing a valuable resource for neuroscience research. Additionally, the methods used to construct the wiring diagram of the fruit fly brain have paved the way for future large-scale connectome projects in other species, including mammals such as mice, which constitute the next target.
“Mapping the entire brain has been made possible thanks to advances in artificial intelligence,” emphasizes Sebastian Seung, a researcher at Princeton University and one of the leaders of the research. “It would not have been possible to manually reconstruct the entire wiring diagram. This is an example of how AI can advance neuroscience. “The fly brain is an important step on our path toward reconstructing a wiring diagram 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 was the result of a collective effort involving teams from more than 76 laboratories and 287 researchers from around the world. the world. This research was carried out using the brain of a female fly. Since there are differences in neuronal structure between the brains of male and female flies, the researchers also plan to characterize a male brain in the future.
“If we want to understand how the brain works, we need a mechanistic understanding of how all the neurons come together and allow us to think,” explains Gregory Jefferis, one of the co-leaders of the research. “For most brains, we 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 the National Institutes of Health, which partially funded the FlyWire project.
We hope that in the future it will be possible to compare what happens when things go wrong in our brains, for example with mental health disorders.
Mala Murthy
— Researcher at Princeton University, co-director of research
“We hope this will have a transformative effect for neuroscientists trying to better understand how a healthy brain works,” concludes Mala Murthy, a researcher at Princeton University and co-leader of the research. “In the future, we hope it will be possible to compare what happens when things go wrong in our brains, for example with mental health disorders. »
A “titanic effort”
Juan Lerma, researcher at the Institute of Neurosciences of Alicante, underlines the “titanic effort” required to create the map of connections of Drosophila and the importance of the calculation algorithms currently being developed. “The authors took into account the previous description of a hemibrain (hemibrain) and did not find large differences, indicating that the variability between individuals is not large and therefore these very detailed data are generalizable to the fly brain. fury“, he explains to elDiario.es. For Lerma, having this very precise connectomic map, also openly available, “means the first step in modeling this brain to answer important questions, particularly in terms of sensory integration, to which a large part of this brain is dedicated”.
These results open new possibilities for studying the mechanisms underlying cognitive, behavioral and neurological disorders.
Javier de Felipe
— Neuroscientist at the Cajal-CSIC Institute
Spanish neuroscientist Javier de Felipe, from the Cajal-CSIC Institute, believes that having a complete connectome allows structure to be correlated with function, providing a framework for studying how genetic or molecular changes affect the brain and behavior. According to him, technological advances making it possible to carry out large-scale reconstructions of the brain using electron microscopy constitute a real revolution in neuroscience. “They offer an unprecedented level of detail on the structure and connectivity of the brain, which opens new possibilities for studying the mechanisms underlying cognition, behavior and neurological disorders,” he emphasizes. ”
Javier Morante Oria, senior researcher at CSIC, believes that having the complete connectome is a big step forward and recalls that, although the fly is a model mechanism and a small insect, it has complex behaviors. “They are simpler organisms, but they perform the same functions as us; They eat, reproduce and sleep,” he says. “This is the way to know the essential and general principles, to understand how neurons connect and to be able to use them for clinical applications in the future.”
Sergio Casas Tintó, researcher at the Carlos III Health Institute (ISCIII) who carries out research on Drosophilabelieves that this work sets a crucial precedent for the exploration of other brains, notably those of vertebrates and humans. “This technology will enable detailed analysis of synaptic connections, which will transform the diagnosis and treatment of neurodegenerative diseases and psychiatric disorders, such as Alzheimer’s disease, Parkinson’s disease, brain tumors, schizophrenia or depression,” he said. Of course, he cautions, the differences between the fly’s brain and those of other organisms, such as mammals, require further research. “And future work should address variability between individuals or between sexes, which could be relevant in studies of neurodiversity or functional specialization. »
