Complete male fly CNS map lists 166,000 neurons, enabling direct comparison with female brain

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Scientists have completed a detailed wiring diagram of the adult male fruit fly central nervous system, tracing more than 166,000 neurons and the millions of connections that link them. The new male map can now be compared directly with a female connectome unveiled in 2024, offering a fresh way to probe how neural circuits drive sex-specific behaviors.

What the map contains

Researchers reconstructed every neuron in the male fly’s brain and its ventral nerve cord — the insect analogue of a spinal cord — producing the first full male central nervous system connectome. The dataset captures both the brain’s two optic lobes and the nerve cord beneath, cataloguing neurons and the synaptic links between them.

High-resolution electron microscopy image of insect brain tissue used for connectomics
Electron-microscopy data underpins the full male fly CNS reconstruction.

The male map complements a previously released female connectome that covers about 140,000 neurons. Taken together, the paired datasets enable direct anatomical comparisons between sexes at single-cell resolution.

New insights into behavior and sensation

Teams that used the map report several immediate findings. One study focused on taste circuits, tracing receptors on the legs, wings, mouthparts and throat back to brain pathways that influence feeding, swallowing and locomotion. That wiring helps fruit flies decide whether a food source is safe.

Diagram showing taste receptor neurons on fly leg and mouthparts traced to brain circuits
Tracing taste receptors on legs and mouthparts back to brain pathways reveals feeding circuits.

Another analysis showed that visual processing extends far deeper into the fly brain than previously recognized, involving more than half of the roughly 11,000 neuron types identified in the map. A third study uncovered a cluster of neurons unique to males that appears to coordinate male-specific actions such as courtship routines and certain forms of aggression — behaviors that differ from female responses. For example, female flies more commonly headbutt, while males tend to lunge.

Why researchers say the map matters

Mapping both sexes offers a new way to home in on the precise neurons that produce behavioral differences. As study co-author Gerry Rubin, head of biology at HHMI’s Janelia Research Campus, put it: “It is the first time we can compare both sexes of an animal with complex social behavior.” He added that the resource makes it easier to identify the neurons underlying those differences.

Champalimaud Foundation investigator Carlos Ribeiro, whose team contributed to the taste-mapping work, described the fly nervous system as an efficient platform for studying computation with relatively few neurons. He said the architecture revealed by the connectome could suggest principles useful for designing more efficient artificial systems.

Technical and scientific reach

Scientists involved in the effort say the project also serves as a technical blueprint for larger connectomics efforts, potentially informing work on vertebrates. In the short term, teams plan to map the brains of larval zebrafish and adult danionin fish. The longer-term ambition is to use comparative circuit maps to better understand how vertebrate brains generate complex behaviors and to shed light on the neural basis of human neurological and psychiatric disorders.

Publication and contributors

The male fly connectome was first released as a preprint and was published in the journals Cell and Current Biology on Thursday (Sept. 3). The datasets and animations were produced by the FlyEM Project Team at HHMI’s Janelia Research Campus in collaboration with the Cambridge Connectomics Group and Google Research.

Researchers say the resource will function as both a discovery tool and a starting point for experiments: by identifying candidate sensory and intermediate neurons, scientists can more quickly design manipulations to test how specific circuits control behavior. As one contributor described it, the map is a practical “hypothesis-generation” platform for targeted follow-up studies.

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