Researchers mapped all 166,700 neurons in a male fly’s brain and compared it to the female map, revealing how the same smell triggers opposite behaviors.
Male and female fruit flies can smell the exact same odor from another fly and respond in opposite ways: one turns aggressive, the other starts courting. Scientists have now mapped the wiring behind that split-second decision, at the level of every single neuron.
An international team co-led by the University of Cambridge has produced the first full-scale wiring map, known as a “connectome,” of a male Drosophila fly’s brain and nerve cord. The map covers all 166,700 neurons and the millions of connections between them, and it’s the first full-scale connectome of any adult animal’s brain and nerve cord ever produced.
The Scale of the Map
Because the female Drosophila brain had already been mapped by the same research group, the new male connectome let researchers directly compare male and female wiring for the first time, at the level of individual neurons and their connections. The entire dataset is now publicly available as a reference for other researchers.
Same Smell, Opposite Behaviors
The comparison revealed that neurons can reroute identical sensory information into entirely different, sex-specific behavioral circuits. A male fly detecting the smell of another male responds with aggression. A female fly detecting the exact same smell responds with courtship behavior instead.
Dr Isabella Beckett, a researcher at the MRC Laboratory of Molecular Biology and one of the study’s lead authors, described what the map reveals: “This work is revealing how brains take the same sensory input and turn it into different behaviours depending on their sex. Seeing those differences is finally helping us to understand how sensory inputs drive behaviour, and to better understand the black box we call the brain.”
The study, published in the journal Cell, was co-led by Dr Greg Jefferis’s group at Cambridge’s Department of Zoology and the MRC Laboratory of Molecular Biology.
Building the Map Took AI and Years of Human Checking
To generate the connectome, collaborators at the Janelia Research Campus sliced a male fly’s entire nervous system into extremely thin sections, then scanned them using high-resolution electron microscopy, producing millions of images of individual nerve cells and their connections. AI was then used to assemble those images into a full 3D map, reconstructing each neuron and identifying the synapses where they communicate.
Even with AI doing the heavy lifting, human verification of the results took the equivalent of 44 years of human labor.
Dr Philipp Schlegel, a researcher at Cambridge and the MRC Laboratory of Molecular Biology who worked on the project, said the resulting dataset opens far more doors than this one study: “This full wiring diagram has massive potential. We’ve produced data that will enable all sorts of new studies into how the brain works and controls behaviours.”
Why This Matters Beyond Flies
Dr Marta Costa, another Cambridge researcher involved in the work, framed the discovery as a starting point rather than an endpoint: “This work has given us a blueprint that pinpoints the location of changes in male and female fly brains, and what types of cells are involved. It’s the first step in understanding the evolutionary processes that have led to these changes.”
Understanding how a healthy brain is wired also helps researchers understand what goes wrong in a diseased one. Three related papers, covering taste and feeding circuits, visual processing pathways, and networks of sexually dimorphic neurons controlling social behavior, were published alongside the main study.
The work was carried out with collaborators at the Janelia Research Campus, the MRC Laboratory of Molecular Biology, and Google Research, and was funded primarily by UKRI’s Medical Research Council and the Wellcome Trust.