Scientists have made a significant breakthrough in understanding the human brain by creating a detailed roadmap of the brain structure, known as a ‘connectome’, neuron by neuron and synapse by synapse, in the brain of an adult fruit fly (Drosophila melanogaster). Previously, efforts had been made to map the brain of a simpler organism, the C. elegans worm, with its 302 neurons, as well as the larval stage of the fruit fly, which consists of 3,000 neurons. However, the adult fruit fly’s brain is vastly more intricate, featuring nearly 140,000 neurons and approximately 50 million synapses that link them. This comprehensive brain map is the result of collaboration among advanced artificial intelligence, gamers, expert tracers, and neuroscientists. The significance of this connectome lies not just in the complexity of the adult Drosophila’s brain but also in the fact that fruit flies exhibit many behaviors similar to humans and share around 75% of the genetic basis for human diseases.
A team of scientists from Princeton has created the inaugural neuron-by-neuron and synapse-by-synapse roadmap of an adult fruit fly’s brain (Drosophila melanogaster), achieving a significant milestone in brain research. This study appears as the lead article in the special October 2 issue of Nature, which focuses entirely on the new fruit fly “connectome.”
Earlier studies mapped the simple brain of a C. elegans worm, with only 302 neurons, and the brain of a larval fruit fly that has 3,000 neurons. In contrast, the adult fruit fly brain is much more elaborate, with nearly 140,000 neurons and around 50 million synapses connecting them.
Fruit flies share about 60% of their DNA with humans, and 75% of human genetic diseases have equivalents in fruit flies. Thus, studying their brains is a crucial step towards comprehending the brains of more complex beings, such as humans.
“This represents a substantial accomplishment,” commented Mala Murthy, the director of the Princeton Neuroscience Institute and co-leader of the research team along with Sebastian Seung. “There is currently no other complete brain connectome for an adult animal of this sophistication.” Murthy also holds the title of Karol and Marnie Marcin ’96 Professor of Neuroscience at Princeton.
Princeton’s Seung and Murthy are the co-senior authors of the main article in the Nature issue, which includes nine associated papers with overlapping authorship. The research is a collaborative effort involving scholars from Princeton University, the University of Vermont, the University of Cambridge, UC Berkeley, UC Santa Barbara, Freie Universität-Berlin, and the Max Planck Florida Institute for Neuroscience. This work received partial funding from the NIH’s BRAIN Initiative, and other neuroscience centers and funds detailed at the document’s end.
The map was produced by the FlyWire Consortium, located at Princeton University, which includes teams from over 76 laboratories and features 287 researchers from across the globe, as well as voluntary gamers.
Sven Dorkenwald, the leading author of the main article in Nature, took charge of the FlyWire Consortium.
“What we’ve created can be described as an atlas,” explained Dorkenwald, a 2023 Ph.D. graduate from Princeton now affiliated with the University of Washington and the Allen Institute for Brain Science. “Just as you wouldn’t set out for a new destination without using Google Maps, you shouldn’t explore the brain without a map. We’ve crafted an atlas of the brain, complete with annotations that feature all the establishments, buildings, and street names. This provides researchers the tools to navigate the brain thoughtfully as we strive to understand it.”
Much like a map that outlines every narrow street as well as various highways, this fly connectome illustrates connections in the fruit fly brain across all scales.
The map was constructed using 21 million images of a female fruit fly brain taken by a research team led by Davi Bock, who was previously at the Howard Hughes Medical Institute’s Janelia Research Campus and currently works at the University of Vermont. An AI model crafted by researchers and software engineers collaborating with Princeton’s Sebastian Seung transformed the raw images into a labeled, three-dimensional representation. Instead of keeping their findings private, the researchers made their developing neural map available to the scientific community from the outset.
“Advancements in AI computing have made mapping the whole brain feasible. It was impractical to manually reconstruct the entire wiring scheme. This exemplifies how AI can advance neuroscience,” stated Prof. Sebastian Seung, a co-leader of the research and an Evnin Professor in Neuroscience at Princeton, as well as a professor of computer science.
“Now that we possess this brain map, we can finally connect which neurons are linked to specific behaviors,” remarked Dorkenwald.
This advancement could pave the way for personalized treatments for brain disorders.
“In many ways, the brain surpasses any computer created by humans, yet we still largely lack understanding of its fundamental principles,” expressed John Ngai, director of the U.S. National Institutes of Health’s BRAIN Initiative, which provided partial sponsorship for the FlyWire project. “Without an in-depth understanding of how neurons interconnect, we cannot grasp the basic mechanisms that dictate healthy brain function or the malfunctions seen in disease.”
