The NIH-supported milestone will advance understanding of brain processes in larger animals
• Press release
A scientific team supported by the National Institutes of Health (NIH) has revealed the first complete map of the neural connections of the brain of the common fruit fly. The map provides a wiring diagram, known as a connectome, and is the largest and most complete adult animal connectome ever created. This work offers critical insights into how brains are connected and the signals that underlie healthy brain functions. The study, which describes more than 50 million connections between more than 130,000 neurons, appears as part of a package of nine journal articles Nature.
“The derogatory fruit fly is surprisingly sophisticated and has served as a powerful model for understanding the biological underpinnings of behavior,” he said. John Ngai, Ph.D. director of NIH’s Brain research through the Initiative to Advance Innovative Neurotechnologies® or The BRAIN Initiative® . “This milestone not only provides researchers with a new set of tools for understanding how circuits in the brain drive behavior, but also serves as an important precursor to ongoing BRAIN-funded efforts to map the connections of larger mammalian brains and people.”
The connectivity map details the complete set of cell classes in the fruit fly brain, identifying different types of neurons and chemical connections, or synapses, between neurons. It also provides information about the type of neurotransmitter (chemicals such as dopamine or serotonin) released 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 in the fly brain. It allows detailed mapping of specific brain circuits that control behavior, such as the eye brain circuit, which receives visual stimuli and outputs behavioral changes that orient the fly’s body during flight.
In an accompanying paper, the researchers provided an annotation of the fly ligament, detailing cell types, cell classes, and more. It includes information critical to 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 linkage project. For example, they can form long-term memories, engage in social interactions, and navigate long distances. Now that the fruit fly connection has been established, the same methodology could be used to rapidly create similar maps in animals with larger brains. For example, the new map can serve as a reference for understanding how a series of human mutations affect brain connections.
To create the fly connectome, the researchers took electron microscope images of the complete fly brain that had been made public and used a computer program to automatically identify or “segment” neurons in images. The program is not foolproof, so the researchers created a computational toolkit that allowed a large online research community to examine the segments, correct them for accuracy, and annotate cell types and classes in a community-driven way. Correction of identification and delineation of single neurons was completed by a fruit consortium labs, called FlyWire, which included scientists from around the world.
“In 2021, only 15% of neurons had been fixed,” said Shelli Avenevoli, Ph.D., associate director of the NIH’s National Institute of Mental Health. we were quickly able to complete this connection.”
Data analysis tools for the complete fruit fly link can be found at https://codex.flywire.ai/ . Researchers can interact with login data at https://fafb-flywire.catmaid.org/ . The study was supported by NIH’s The BRAIN Initiative, an interdisciplinary collaboration between 10 NIH institutes and centers This enables researchers to understand the brain in unprecedented levels of detail in both health and disease, improving how we treat, prevent and treat brain disorders.
Brain Research through Advancing Innovative Neurotechnologies® The Initiative and The BRAIN Initiative® are registered trademarks of the US Department of Health and Human Services.
References
Dorkenwald, S., Matsliah, A., Sterling, AR, Schlegel, P., Yu, S., McKellar, CE, Lin, A., Costa, M., Eichler, K., Yin, Y., Silversmith, W., Schneider-Mizell, C., Jordan, CS, Brittain, D., Halageri, A., Kuehner, K., Ogedengbe, O., Morey, R., Gager, J., … FlyWire Consortium. (2024). Neuronal wiring diagram of an adult brain. Nature. https://www.nature.com/articles/s41586-024-07558-y
Schlegel, P., Yin, Y., Bates, AS, Dorkenwald, S., Eichler, K., Brooks, P., Han, DS, Gkantia, M., dos Santos, M., Munnelly, EJ, Badalamente, G., Capdevila, LS, Sane, VA, Fragniere, AMC, Kiassat, L., Pleijzier, MW, Stürner, T., Tamimi, IFM, Dunne, CR, … Jefferis, GSXE (2024). Whole brain annotation and multilink cell typing Drosophila. Nature. https://www.nature.com/articles/s41586-024-07686-5
Grants
MH117815 , MH129268 , MH120679 , NS126935
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About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is part of the US Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research and investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit it NIH website .
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