This map shows the precise location and arrangement of the 50 largest neurons of the fly brain connectome. These 50, along with another 139,205 brain cells in the brain of an adult fruit fly, were painstakingly mapped by a Princeton University-led team of neuroscientists, gamers and professional tracers. Activity within these neurons (brain cells) drives everything the organism does, from sensory perception to decision-making to controlling flight. The brain cells are connected by more than 50 million connections (synapses). Find more here: https://doi.org/10.1038/s41586-024-07558-y [Tyler Sloan and Amy Sterling / FlyWire / Princeton University]
In a major neuroscience milestone, a team of scientists has mapped the entire brain of an adult Drosophila melanogaster, building the first neuron-by-neuron and synapse-by-synapse roadmap. This research is published in two papers, in a special issue of Nature: “Neuronal wiring diagram of an adult brain,” and “Whole-brain annotation and multi-connectome cell typing of Drosophila.” The issue of Nature is devoted to the new Drosophila connectome and includes a suite of related papers.
Previous researchers mapped the brain of C. elegans, with its 302 neurons, and the brain of a larval fruit fly, which had 3,000 neurons, but the adult fruit fly holds almost 140,000 neurons and roughly 50 million synapses.
“This is a major achievement,” said Mala Murthy, PhD, director of the Princeton Neuroscience Institute. “There is no other full brain connectome for an adult animal of this complexity.”
The map was developed by the FlyWire Consortium, which is based at Princeton University and made up of teams in more than 76 laboratories with 287 researchers around the world as well as volunteer gamers.
The map was built from 21 million images taken of a female fruit fly brain, using an AI model. The scientists found that there were substantial similarities between the wiring in this map and previous smaller-scale efforts that have mapped out parts of the fly brain. This led the researchers to conclude that there are many similarities in wiring between individual brains.
When comparing their brain diagram to previous diagrams of small areas of the brain, the researchers also found that about 0.5% of neurons have developmental variations which could cause connections between neurons to be miswired. The researchers say this will be an important area for future research to understand if these changes are linked to individuality or brain disorders.
A whole fly brain is less than 1 mm wide. The researchers started with one female brain cut into seven thousand slices, each only 40 nanometers thick, that were previously scanned using high-resolution electron microscopy.
Analyzing over 100 terabytes of image data (equivalent to the storage in 100 typical laptops) to extract the shapes of about 140,000 neurons and 50 million connections between them is too big a challenge for humans to complete manually. The researchers built on AI developed at Princeton University to identify and map neurons and their connections to each other.
They also annotated many details on the wiring diagram, such as classifying more than 8,000 cell types across the brain.
“Mapping the whole brain has been made possible by advances in AI computing. It would have not been possible to reconstruct the entire wiring diagram manually. This is a display of how AI can move neuroscience forward,” said Sebastian Seung, PhD, professor of neuroscience and computer science at Princeton University.
This research was conducted using a female fly brain. Since there are differences in neuronal structure between male and female fly brains, the researchers plan to also characterize a male brain in the future.
“We have made the entire database open and freely available to all researchers,” said Muthy. “We hope this will be transformative for neuroscientists trying to better understand how a healthy brain works. In the future, we hope that it will be possible to compare what happens when things go wrong in our brains, for example in mental health conditions.”
The researchers also created a map of projections between brain regions, known as a projectome, that tracks the organization of the hemispheres and behavioral circuits within the fly brain. It allows for the detailed mapping of specific brain circuits that control behavior, such as the ocellar brain circuit, which takes in visual stimuli and outputs behavioral changes that orient the fly’s body during flight.
In a companion paper, the researchers provided an annotation of the fly connectome, detailing cell types, cell classes, and more. It includes information critical for researchers and others who will use the connectome to advance our understanding of brain physiology and behavior.
Data analysis tools for the full fruit fly connectome can be found at codex.flywire.ai. Researchers can interact with the connectome data at fafb-flywire.catmaid.org.
