Scientists have mapped the position, shape, and connections of each of its 130,000 cells and 50 million neural connections of a fly’s brain.
Walking, hovering, and even producing melodic love songs are all feats managed by fruit flies—achieved with a brain no larger than a pinhead.
One prominent neuroscientist described this development as a “huge leap” toward a deeper understanding of the human brain.
According to a research leader, this mapping brings valuable insights into “the mechanism of thought,” illuminating how neural networks enable interaction with both others and the surrounding world.
Dr. Gregory Jefferis of the Medical Research Council’s Laboratory of Molecular Biology (LMB) explained that currently, little is known about how the complex web of brain cells processes sensory information, allowing for facial recognition, auditory perception, and the translation of words into electrical signals.
The wiring diagram of the fly brain, though vastly simpler, is seen as a remarkable tool that may guide scientists toward a clearer understanding of human cognition and brain function, despite humans having over a million times more neurons than the fly.
Images produced by the scientists, recently published in the journal Nature, reveal a stunningly intricate web of neural wiring—both complex and aesthetically captivating.
This structure, in its shape and organization, may hold essential clues to understanding how such a minuscule brain performs so many powerful computational functions. Designing a computer the size of a poppy seed with similar capabilities remains far beyond the reach of current technology.
Dr. Mala Murthy of Princeton University, a co-leader of the project, described the new wiring map, known as a connectome, as “transformative for neuroscientists.”
“It will support researchers striving to understand the functions of a healthy brain. In the future, it may even offer a means to explore what happens when brain function falters.”
Dr. Mala Murthy
Dr. Lucia Prieto Godino, a brain research group leader at the Francis Crick Institute in London, independently noted the significance of this achievement:
“Researchers have completed the connectomes of a simple worm with 300 neural connections and a maggot with three thousand, but completing the connectome of a brain with 130,000 connections is a remarkable technical breakthrough. This success paves the way for mapping connectomes of larger brains, such as the mouse—and perhaps, in time, even our own.”
Dr. Lucia Prieto Godino
Researchers have pinpointed distinct circuits for various individual functions and revealed the connections between them. For example, movement circuits reside at the brain’s base, while vision processing circuits, which require much more neural power, are positioned toward the side. While the presence of separate circuits was previously known, the interconnections between them had remained a mystery until now.
Flies, famously challenging to swat, may owe this agility to their rapid-response circuitry. Researchers have begun using detailed circuit diagrams of the fly brain to understand these remarkable reflexes.
The vision circuits in flies detect the direction of an approaching object, such as a rolled-up newspaper, and transmit this signal to the legs. Interestingly, a stronger jump signal is sent to the legs on the side opposite the object, prompting a rapid escape. This reflexive action is so quick that it occurs faster than the speed of conscious thought, potentially explaining why humans rarely succeed in catching flies.
The creation of this intricate wiring map involved slicing the fly brain into 7,000 ultra-thin layers, photographing each slice, and then digitally reconstructing them. Artificial intelligence was employed to trace neuron shapes and connections, although millions of corrections were made by hand to ensure accuracy—a technical feat in its own right. Dr. Philipp Schlegel of the Medical Research Council’s Laboratory of Molecular Biology likens this data to “Google Maps for brains”: while the wiring diagram provides structural insights, a detailed description of each neuron’s function adds context, much like the labels and information on a geographic map.
Now accessible to scientists worldwide, this fly connectome promises to accelerate discoveries in neuroscience. Dr. Schlegel anticipates “an avalanche of discoveries in the next couple of years” thanks to this open resource.
Mapping the vastly larger human brain remains beyond current technology, but researchers hope that, within 30 years, a complete human connectome may be possible. This work on the fly brain represents a promising step toward a more profound understanding of human cognition.
This research has been conducted by the FlyWire Consortium, an international team dedicated to unraveling neural connectivity.
https://www.nature.com/articles/s41586-024-07686-5
Abstract
The fruit fly Drosophila melanogaster has emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome1 with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome2, and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and we validate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics.
