by Princeton University

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). Credit: Tyler Sloan and Amy Sterling / FlyWire / Princeton University

A Princeton-led team of scientists has built the first neuron-by-neuron and synapse-by-synapse roadmap through the brain of an adult fruit fly (Drosophila melanogaster), marking a major milestone in the study of brains. This research is the flagship article in the Oct. 2 special issue of Nature, which is devoted to the new fruit fly "connectome."

Previous researchers mapped the brain of a C. elegans worm, with its 302 neurons, and the brain of a larval fruit fly, which had 3,000 neurons, but the adult fruit fly is several orders of magnitude more complex, with almost 140,000 neurons and roughly 50 million synapses connecting them.

Fruit flies share 60% of human DNA, and three in four human genetic diseases have a parallel in fruit flies. Understanding the brains of fruit flies is a steppingstone to understanding brains of larger more complex species, like humans.

Credit: Tyler Sloan / FlyWire / Princeton University

This is a major achievement," said Mala Murthy, director of the Princeton Neuroscience Institute and, with Sebastian Seung, co-leader of the research team. "There is no other full brain connectome for an adult animal of this complexity." Murthy is also Princeton's Karol and Marnie Marcin '96 Professor of Neuroscience.

Princeton's Seung and Murthy are co-senior authors on the flagship paper of the Nature issue, which includes a suite of nine related papers with overlapping sets of authors, led by researchers from Princeton University, the University of Vermont, the University of Cambridge, the University of California-Berkeley, UC-Santa Barbara, Freie Universität-Berlin, and the Max Planck Florida Institute for Neuroscience.

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.

This image is a video still showing the brain inside an adult fruit fly. Credit: Amy Sterling / FlyWire / Princeton University

Sven Dorkenwald, the lead author on the paper, spearheaded the FlyWire Consortium.

"What we built is, in many ways, an atlas," said Dorkenwald, a 2023 Ph.D. graduate of Princeton now at the University of Washington and the Allen Institute for Brain Science.

"Just like you wouldn't want to drive to a new place without Google Maps, you don't want to explore the brain without a map. What we have done is build an atlas of the brain, and added annotations for all the businesses, the buildings, the street names. With this, researchers are now equipped to thoughtfully navigate the brain as we try to understand it."

And just like a map that traces out every tiny alley as well as every superhighway, the fly connectome shows connections within the fruit fly brain at every scale.

The map was built from 21 million images taken of a female fruit fly brain by a team of scientists led by Davi Bock, then at the Howard Hughes Medical Institute's Janelia Research Campus and now at the University of Vermont.

Using an AI model built by researchers and software engineers working with Princeton's Sebastian Seung, the lumps and blobs in those images were turned into a labeled, three-dimensional map. Instead of keeping their data confidential, the researchers opened their in-progress neural map to the scientific community from the beginning.

This image shows the complete fruit fly connectome: all 139,255 brain cells in the brain of an adult fruit fly. Activity within these neurons drives an entire organism, from sensory perception to decision-making to flying. These neurons are connected by more than 50 million connections (synapses). A Princeton-led team of gamers, neuroscientists and professional tracers painstakingly mapped out the locations and connections of every brain cell, using 21 million images. Credit: Tyler Sloan / FlyWire / Princeton University

"Mapping the whole brain has been made possible by advances in AI computing. It would not have been possible to reconstruct the entire wiring diagram manually. This is a display of how AI can move neuroscience forward," said Prof. Sebastian Seung, one of the co-leaders of the research and Princeton's Evnin Professor of Neuroscience and a professor of computer science.

"Now that we have this brain map, we can close the loop on which neurons relate to which behaviors," said Dorkenwald.

The development could lead to tailored treatments for brain diseases.

"In many respects, it (the brain) is more powerful than any human-made computer, yet for the most part we still do not understand its underlying logic," said John Ngai, director of the U.S. National Institutes of Health's BRAIN Initiative.

"Without a detailed understanding of how neurons connect with one another, we won't have a basic understanding of what goes right in a healthy brain or what goes wrong in disease."

More information: Neuronal wiring diagram of an adult brain, Nature (2024). DOI: 10.1038/s41586-024-07558-y. www.nature.com/articles/s41586-024-07558-y

Journal information: Nature 

Provided by Princeton University