Janelia closes its 18-year fly connectome bet with all 166,000 neurons mapped

Janelia researchers published in Cell the connectome of the full central nervous system of a fruit fly: a wiring diagram of more than 166,000 neurons making up the fly's brain and ventral nerve cord, and the millions of connections between them.

Janelia is applying lessons from the fly connectome to new animal models with the ultimate goal of providing the first mechanistic account of how a vertebrate brain generates behavior.

The new map charts the male fruit fly's brain and the insect's equivalent of a spinal cord, and joins a map of a female fruit fly brain unveiled in 2024 that covers about 140,000 neurons.

Researchers at HHMI's Janelia Research Campus set out in 2008 to create a map of all the neurons in the fruit fly brain, and many in the scientific community thought they were out of their minds; most scientists thought mapping the fly brain, with more than 100,000 neurons, would take too long, cost too much, and not tell them much about how the brain worked.

The connectome of the 302 neurons of the worm C. elegans took more than a decade and had been unveiled 20 years before Janelia began the fly project.

The team estimated that with the technology available when they started in 2008, creating the fly connectome would take 500 people working for 10 years, a time and cost they judged had to be reduced through technological improvement.

Researchers led by senior group leader Harald Hess spent years optimizing and scaling up a pioneering microscopy technique for sharper images of individual neurons, while other teams working with collaborators at Google Research developed computational methods to speed up image interpretation.

In 2020 the researchers unveiled the hemibrain, a map of half the fly brain covering 25,000 neurons, which was the biggest and most detailed connectome ever created at that point and proved the feasibility and utility of a fly brain map.

The new fly brain map, initially released as a preprint, was published in the journals Cell and Current Biology on Thursday, Sept. 3, alongside three other papers each using the new data to explore a specific aspect of fruit fly neurobiology.

One companion paper showed that visual processing extends deep into the fly brain, involving more than half of the roughly 11,000 types of neurons identified in the map.

Another companion paper found a network of cells specific to the male brain that appears to coordinate male-specific behaviors such as particular aspects of courtship and physical aggression.

The research found that while some networks are specific to each sex, the circuits for sensation and movement are largely shared between males and females, with specific switches within those circuits rerouting signals to different destinations in the male and female brain.

Study co-author Ines de Haan Vicente, a research technician in Ribeiro's lab, called the diagram of taste processing a "hypothesis-generation tool" that gives researchers a place to start when asking which sensory neurons connect to neurons controlling locomotion.

The Champalimaud-led study identified fruit fly taste receptors in the legs, wings, mouthparts and inside of the throat, traced their connections back to the brain, and examined how those circuits interacted with circuits governing behaviors such as swallowing or walking.

Female flies tend to headbutt their targets while males lunge at them.

Eighteen years separate the 2008 start of the Janelia fly connectome project from the September 2026 publication of the full central nervous system map.

The male central nervous system map's 166,000 neurons exceed the 2024 female brain map's roughly 140,000 by about 26,000, but the male figure covers brain plus ventral nerve cord while the female figure covers the brain.

The fly central nervous system map covers roughly 550 times as many neurons as the 302-neuron C. elegans connectome.

Going from the 2020 hemibrain's 25,000 neurons to the 166,000 of the full central nervous system map is an increase of about 6.6 times.

Gerry Rubin says Janelia's key contribution was the leap of faith that it could assemble an interdisciplinary team who would develop ways to increase the efficiency of generating connectomes by more than 1,000-fold, without which "we could still be waiting."

Carlos Ribeiro of the Champalimaud Foundation in Lisbon said the fly nervous system performs remarkably sophisticated computations with relatively few neurons and little energy, and its architecture could suggest principles for designing more efficient artificial systems.

Ribeiro said the work provides a technical roadmap for more ambitious connectomics projects in future, such as those for mice and humans.

The 2008 estimate of 500 people for 10 years amounts to 5,000 person-years; a thousandfold efficiency gain applied to that figure would imply about 5 person-years, which is inconsistent with a project that ran 18 years.