by National Institutes of Health

50 largest neurons of the fly brain connectome. Credit: Tyler Sloan and Amy Sterling for FlyWire, Princeton University, (Dorkenwald et al., Nature, 2024)

A scientific team has unveiled the first complete map of the neural connections of the common fruit fly brain. The map provides a wiring diagram, known as a connectome, and is the largest and most complete connectome of an adult animal ever created. This work offers critical information about how brains are wired and the signals that underlie healthy brain functions.

The study, which details over 50 million connections between more than 130,000 neurons, appears as part of a package of nine papers in the journal Nature.

"The diminutive fruit fly is surprisingly sophisticated and has long served as a powerful model for understanding the biological underpinnings of behavior," said John Ngai, Ph.D., director of NIH's Brain Research Through Advancing Innovative Neurotechnologies Initiative, or The BRAIN Initiative.

"This milestone not only provides researchers with a new set of tools for understanding how the circuits in the brain drive behavior, but importantly serves as a forerunner to ongoing ... efforts to map the connections of larger mammalian and human brains."

The connectome map details the full set of cell classes in the fruit fly brain, identifying different types of neurons and chemical connections, or synapses, between neurons. It also provides insight into the type of neurotransmitter (chemicals such as dopamine or serotonin) secreted by each neuron.

The researchers also created a map of projections between brain regions, known as a projectome, that tracks the organization of the hemispheres and behavioral circuits within the fly brain. It allows for the detailed mapping of specific brain circuits that control behavior, such as the ocellar brain circuit, which takes in visual stimuli and outputs behavioral changes that orient the fly's body during flight.

All 139,255 brain cells in the brain of an adult fruit fly. Activity within these cells drives an entire organism, from sensory perception to decision making and the control of actions, such as flying. They are connected by over 50 million synaptic connections. Credit: Tyler Sloan for FlyWire, Princeton University, (Dorkenwald et al., Nature, 2024)

In a companion paper, the researchers provided an annotation of the fly connectome, detailing cell types, cell classes, and more. It includes information critical for researchers and others who will use the connectome to advance our understanding of brain physiology and behavior.

The fruit fly is capable of surprisingly advanced cognition and behavior, making it an ideal candidate for this initial connectome project. For example, they can form long-term memories, engage in social interactions, and navigate over long distances.

Now that the fruit fly connectome has been established, the same methodology could be used to rapidly create similar maps in larger-brained animals. For example, the new map may serve as a reference to understand how a host of human mutations affect brain connections.

To create the fly connectome, researchers took electron microscope images of the complete fly brain that had been publicly released and used a computer program to automatically identify or "segment" the neurons in the images.

The program is not foolproof, so the researchers created a computational system of tools that allowed a large online research community to look at the segments, proofread them for accuracy, and annotate cell types and classes in a community-driven manner.

Proofreading of the identification and delineation of the individual neurons was completed by a consortium of fruit fly labs, called FlyWire, which included scientists from around the world.

"In 2021, only 15% of the neurons had been proofread," said Shelli Avenevoli, Ph.D., acting director of NIH's National Institute of Mental Health. "Opening proofreading to the larger scientific community studying the fruit fly brain greatly accelerated how fast we were able to complete this connectome."

Data analysis tools for the full fruit fly connectome can be found at https://codex.flywire.ai/. Researchers can interact with the connectome data at https://fafb-flywire.catmaid.org/.

More information: Dorkenwald, S., et al. FlyWire Consortium. Neuronal wiring diagram of an adult brain. Nature (2024). DOI: 10.1038/s41586-024-07558-y

Schlegel, P., et al. Whole-brain annotation and multi-connectome cell typing of Drosophila. Nature (2024). DOI: 10.1038/s41586-024-07686-5

Journal information: Nature 

Provided by National Institutes of Health