Scientists Map Entire Brain of Adult Fruit Fly, Marking Major Milestone in Neuroscience

First complete map of every neuron in the brain revealed - Earth.com

Imagine gazing at the intricate yet beautiful map of an entire city, but the city is in fact a brain. Sounds fascinating, doesn't it? Well, scientists have now made this a reality. Experts have created the first-ever wiring diagram, or "connectome," of every neuron in an adult brain along with the 50 million connections between them, marking a milestone in the field of neuroscience. The project was made possible by the FlyWire Consortium, a large international collaboration involving scientists from the MRC Laboratory of Molecular Biology in Cambridge, Princeton University, the University of Vermont, and the University of Cambridge. The research, which is published in a pair of papers in the journal Nature, delivers the first complete wiring diagram of all 139,255 neurons in an adult fly brain - an animal capable of both walking and seeing. Previous studies have mapped smaller brain systems like fruit fly larva with 3,016 neurons, or the nematode worm with 302 neurons. However, the current study breaks new ground by offering a full-scale neural map for a more complex organism. The findings offer valuable insights into brain structure and function, providing a vital comparison for ongoing research in neuroscience. "If we want to understand how the brain works, we need a mechanistic understanding of how all the neurons fit together and let you think. For most brains, we have no idea how these networks function," noted study co-author Dr. Gregory Jefferis. The detailed map of the fly's brain could answer many of these questions, unlocking the intricacies of neural circuits. One of the most remarkable revelations of the study is the substantial similarities in the wiring that were found between the current map and previous smaller-scale efforts. This has led to the conclusion that individual brains share inherent similarities in their wiring - contrary to the belief that each brain is a unique structure. The path to this achievement involved slicing a whole fly brain, which measures less than a millimeter wide, into 7,000 thin slices. These slices were then meticulously scanned using high-resolution electron microscopy to extract the shapes of approximately 140,000 neurons and 50 million connections between them. The task of analyzing this enormous amount of data was made possible using machine learning, demonstrating the potential for AI technology to revolutionize neuroscience. Ensuring the accuracy of the data required an estimated 33 person-years for proofreading. Despite the challenges, the outcome of this meticulous endeavor has paved the way for future revelations in neuroscience. Beyond just establishing the neuronal connections, the researchers also interpreted many details of the wiring diagram - such as classifying more than 8,000 cell types across the brain. "This dataset is a bit like Google Maps but for brains: the raw wiring diagram between neurons is like knowing which structures on satellite images of the Earth correspond to streets and buildings," explained Dr. Philipp Schlegel, the first author of one of the studies. The researchers' work extends beyond mere mapping. They have also used AI image scanning technology to predict whether each synapse was inhibitory or excitatory - a crucial aspect for digitally simulating the brain. "Using our data, which has been shared online as we worked, other scientists have already started trying to simulate how the fly brain responds to the outside world," said Dr. Jefferis. "This is an important start, but we will need to collect many different kinds of data to produce reliable simulations of how a brain functions." This research has undoubtedly revolutionized our understanding of the brain, yet the journey is far from over. As we progress, future studies will explore the differences in neuronal structure between male and female fly brains. "The comprehensiveness of our wiring diagram has significant benefits for brain research and enables many kinds of studies that were not previously possible using wiring diagrams of portions of the fly brain," noted the researchers. Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates.

First map of every neuron in an adult brain has been produced for a fruit fly

The first wiring diagram of every neuron in an adult brain and the 50 million connections between them has been produced for a fruit fly. This landmark achievement has been conducted by a large international collaboration of scientists, called the FlyWire Consortium, including researchers from the MRC Laboratory of Molecular Biology (in Cambridge, UK), Princeton University, the University of Vermont and the University of Cambridge. It is published in a pair of papers in Nature. The diagram of all 139,255 neurons in the adult fly brain is the first of an entire brain for an animal that can walk and see. Previous efforts have completed the whole brain diagrams for much smaller brains, for example, for that of a fruit fly larva, which has 3,016 neurons, and a nematode worm, which has 302 neurons. The researchers say the whole fly brain map is a key first step to completing larger brains. Since the fruit fly is a common tool in research, its brain map can be used to advance our understanding of how neural circuits work. Dr. Gregory Jefferis, from the MRC Laboratory of Molecular Biology and from the University of Cambridge, who was one of the co-leaders of the research, said, "If we want to understand how the brain works, we need a mechanistic understanding of how all the neurons fit together and let you think. For most brains, we have no idea how these networks function. "Flies can do all kinds of complicated things like walk, fly, navigate, and the males sing to the females. Brain wiring diagrams are a first step towards understanding everything we're interested in -- how we control our movement, answer the telephone, or recognize a friend." Dr. Mala Murthy, from Princeton University, who was one of the co-leaders of the research, said, "We have made the entire database open and freely available to all researchers. We hope this will be transformative for neuroscientists trying to better understand how a healthy brain works. "In the future, we hope that it will be possible to compare what happens when things go wrong in our brains, for example in mental health conditions." Brains are not snowflakes The scientists found that there were substantial similarities between the wiring in this map and previous smaller-scale efforts which have mapped out parts of the fly brain. This led the researchers to conclude that there are many similarities in wiring between individual brains -- that each brain isn't a unique structure like a snowflake. When comparing their brain diagram to previous diagrams of small areas of the brain, the researchers also found that about 0.5% of neurons have developmental variations which could cause connections between neurons to be mis-wired. The researchers say this will be an important area for future research to understand if these changes are linked to individuality or brain disorders. Making the map A whole fly brain is less than 1 millimeter wide. The researchers started with one female brain cut into seven thousand slices, each only 40 nanometers thick, that were previously scanned using high resolution electron microscopy in the laboratory of project co-leader Davi Bock, then at Janelia Research Campus in the US. Analyzing over 100 terabytes of image data (equivalent to the storage in 100 typical laptops) to extract the shapes of about 140,000 neurons and 50 million connections between them is too big a challenge for humans to complete manually. The researchers built on AI developed at Princeton University to identify and map neurons and their connections to each other. However, the AI still makes many errors in datasets of this size. The FlyWire Consortium -- made up of teams in more than 76 laboratories and 287 researchers around the world, as well as volunteers from the general public -- spent an estimated 33 person-years painstakingly proofreading all the data. Dr. Sebastian Seung, from Princeton University, who was one of the co-leaders of the research, said, "Mapping the whole brain has been made possible by advances in AI computing -- it would not have been possible to reconstruct the entire wiring diagram manually. This is a display of how AI can move neuroscience forward. The fly brain is a milestone on our way to reconstructing a wiring diagram of a whole mouse brain." The researchers also annotated many details on the wiring diagram, such as classifying more than 8,000 cell types across the brain. This also allows researchers to select particular systems within the brain for further study, such as the neurons involved in sight or movement. Dr. Philipp Schlegel, the first author of one of the studies, from the MRC Laboratory of Molecular Biology, said, "This dataset is a bit like Google Maps but for brains: the raw wiring diagram between neurons is like knowing which structures on satellite images of the earth correspond to streets and buildings. "Annotating neurons is like adding the names for streets and towns, business opening times, phone numbers, reviews, et cetera to the map -- you need both for it to be really useful." Simulating brain function This is also the first whole brain wiring map -- often called a connectome -- to predict the function of all the connections between neurons. Neurons use electrical signals to send messages. Each neuron can have hundreds of branches that connect it to other neurons. The points where these branches meet and transmit signals between neurons are called synapses. There are two main ways that neurons communicate across synapses: excitatory (which promotes the continuation of the electrical signal in the receiving neuron), or inhibitory (which reduces the likelihood that the next neuron will transmit signals). Researchers from the team also used AI image scanning technology to predict whether each synapse was inhibitory or excitatory. Dr. Jefferis added, "To begin to simulate the brain digitally, we need to know not only the structure of the brain, but also how the neurons function to turn each other on and off." "Using our data, which has been shared online as we worked, other scientists have already started trying to simulate how the fly brain responds to the outside world. This is an important start, but we will need to collect many different kinds of data to produce reliable simulations of how a brain functions." Associate Professor Davi Bock, who was one of the co-leaders of the research, from the University of Vermont, said, "The hyper-detail of electron microscopy data creates its own challenges, especially at scale. This team wrote sophisticated software algorithms to identify patterns of cell structure and connectivity within all that detail. "We can now make precise synaptic level maps and use these to better understand cell types and circuit structure at whole-brain scale. This will inevitably lead to a deeper understanding of how nervous systems process, store and recall information. I think this approach points the way forward for the analysis of future whole-brain connectomes, in the fly as well as in other species." This research was conducted using a female fly brain. Since there are differences in neuronal structure between male and female fly brains, the researchers plan to also characterize a male brain in the future.

Largest brain map ever reveals fruit fly's neurons in exquisite detail

A fruit fly might not be the smartest organism, but scientists can still learn a lot from its brain. Researchers are hoping to do that now that they have a new map -- the most complete for any organism so far -- of the brain of a single fruit fly (Drosophila melanogaster). The wiring diagram, or 'connectome', includes nearly 140,000 neurons and captures more than 54.5 million synapses, which are the connections between nerve cells. "This is a huge deal," says Clay Reid, a neurobiologist at the Allen Institute for Brain Science in Seattle, Washington, who was not involved in the project but has worked with one of the team members who was. "It's something that the world has been anxiously waiting for, for a long time." The map is described in a package of nine papers about the data published in Nature today. Its creators are part of a consortium known as FlyWire, co-led by neuroscientists Mala Murthy and Sebastian Seung at Princeton University in New Jersey. Seung and Murthy say that they've been developing the FlyWire map for more than four years, using electron microscopy images of slices of the fly's brain. The researchers and their colleagues stitched the data together to form a full map of the brain with the help of artificial-intelligence (AI) tools. But these tools aren't perfect, and the wiring diagram needed to be checked for errors. The scientists spent a great deal of time manually proofreading the data -- so much time that they invited volunteers to help. In all, the consortium members and the volunteers made more than 3 million manual edits, according to co-author Gregory Jefferis, a neuroscientist at the University of Cambridge, UK. (He notes that much of this work took place in 2020, when fly researchers were at loose ends and working from home during the COVID-19 pandemic.) But the work wasn't finished: the map still had to be annotated, a process in which the researchers and volunteers labelled each neuron as a particular cell type. Jefferis compares the task to assessing satellite images: AI software might be trained to recognize lakes or roads in such images, but humans would have to check the results and name the specific lakes or roads themselves. All told, the researchers identified 8,453 types of neuron -- much more than anyone had expected. Of these, 4,581 were newly discovered, which will create new research directions, Seung says. "Every one of those cell types is a question," he adds. The team was surprised by some of the ways in which the various cells connect to one another, too. For instance, neurons that were thought to be involved in just one sensory wiring circuit, such as a visual pathway, tended to receive cues from multiple senses, including hearing and touch. "It's astounding how interconnected the brain is," Murthy says. The FlyWire map data have been available for the past few years for researchers to explore. This has enabled scientists to learn more about the brain and about fruit flies -- findings that are captured in some of the papers published in Nature today. In one paper, for example, researchers used the connectome to create a computer model of the entire fruit-fly brain, including all the connections between neurons. They tested it by activating neurons that they knew either sense sweet or bitter tastes. These neurons then launched a cascade of signals through the virtual fly's brain, ultimately triggering motor neurons tied to the fly's proboscis -- the equivalent of the mammalian tongue. When the sweet circuit was activated, a signal for extending the proboscis was transmitted, as if the insect was preparing to feed; when the bitter circuit was activated, this signal was inhibited. To validate these findings, the team activated the same neurons in a real fruit fly. The researchers learnt that the simulation was more than 90% accurate at predicting which neurons would respond and therefore how the fly would behave. In another study, researchers describe two wiring circuits that signal a fly to stop walking. One of these contains two neurons that are responsible for halting 'walk' signals sent from the brain when the fly wants to stop and feed. The other circuit includes neurons in the nerve cord, which receives and processes signals from the brain. These cells create resistance in the fly's leg joints, allowing the insect to stop while it grooms itself. One limitation of the new connectome is that it was created from a single female fruit fly. Although fruit-fly brains are similar to each other, they are not identical. Until now, the most complete connectome for a fruit-fly brain was a map of a 'hemibrain' -- a portion of a fly's brain containing around 25,000 neurons. In one of the Nature papers out today, Jefferis, Davi Bock, a neurobiologist at the University of Vermont in Burlington, and their colleagues compared the FlyWire brain with the hemibrain. Some of the differences were striking. The FlyWire fly had almost twice as many neurons in a brain structure called the mushroom body, which is involved in smell, compared with the fly used in the hemibrain-mapping project. Bock thinks the discrepancy could be because the hemibrain fly might have starved while it was still growing, which harmed its brain development. The FlyWire researchers say that much work remains to be done to fully understand the fruit-fly brain. For instance, the latest connectome shows only how neurons connect through chemical synapses, across which molecules called neurotransmitters send information. It doesn't offer any information about electrical connectivity between neurons or about how neurons chemically communicate outside synapses. And Murthy hopes to eventually have a male fly connectome, too, which would allow researchers to study male-specific behaviours such as singing. "We're not done, but it's a big step," Bock says.

Researchers map the entire brain of an adult fruit fly for the first time

A Princeton-led team of scientists has built the first neuron-by-neuron and synapse-by-synapse roadmap through the brain of an adult fruit fly (Drosophila melanogaster), marking a major milestone in the study of brains. This research is the flagship article in the Oct. 2 special issue of Nature, which is devoted to the new fruit fly "connectome." Previous researchers mapped the brain of a C. elegans worm, with its 302 neurons, and the brain of a larval fruit fly, which had 3,000 neurons, but the adult fruit fly is several orders of magnitude more complex, with almost 140,000 neurons and roughly 50 million synapses connecting them. Fruit flies share 60% of human DNA, and three in four human genetic diseases have a parallel in fruit flies. Understanding the brains of fruit flies is a steppingstone to understanding brains of larger more complex species, like humans. This is a major achievement," said Mala Murthy, director of the Princeton Neuroscience Institute and, with Sebastian Seung, co-leader of the research team. "There is no other full brain connectome for an adult animal of this complexity." Murthy is also Princeton's Karol and Marnie Marcin '96 Professor of Neuroscience. Princeton's Seung and Murthy are co-senior authors on the flagship paper of the Nature issue, which includes a suite of nine related papers with overlapping sets of authors, led by researchers from Princeton University, the University of Vermont, the University of Cambridge, the University of California-Berkeley, UC-Santa Barbara, Freie Universität-Berlin, and the Max Planck Florida Institute for Neuroscience. The map was developed by the FlyWire Consortium, which is based at Princeton University and made up of teams in more than 76 laboratories with 287 researchers around the world as well as volunteer gamers. Sven Dorkenwald, the lead author on the paper, spearheaded the FlyWire Consortium. "What we built is, in many ways, an atlas," said Dorkenwald, a 2023 Ph.D. graduate of Princeton now at the University of Washington and the Allen Institute for Brain Science. "Just like you wouldn't want to drive to a new place without Google Maps, you don't want to explore the brain without a map. What we have done is build an atlas of the brain, and added annotations for all the businesses, the buildings, the street names. With this, researchers are now equipped to thoughtfully navigate the brain as we try to understand it." And just like a map that traces out every tiny alley as well as every superhighway, the fly connectome shows connections within the fruit fly brain at every scale. The map was built from 21 million images taken of a female fruit fly brain by a team of scientists led by Davi Bock, then at the Howard Hughes Medical Institute's Janelia Research Campus and now at the University of Vermont. Using an AI model built by researchers and software engineers working with Princeton's Sebastian Seung, the lumps and blobs in those images were turned into a labeled, three-dimensional map. Instead of keeping their data confidential, the researchers opened their in-progress neural map to the scientific community from the beginning. "Mapping the whole brain has been made possible by advances in AI computing. It would not have been possible to reconstruct the entire wiring diagram manually. This is a display of how AI can move neuroscience forward," said Prof. Sebastian Seung, one of the co-leaders of the research and Princeton's Evnin Professor of Neuroscience and a professor of computer science. "Now that we have this brain map, we can close the loop on which neurons relate to which behaviors," said Dorkenwald. The development could lead to tailored treatments for brain diseases. "In many respects, it (the brain) is more powerful than any human-made computer, yet for the most part we still do not understand its underlying logic," said John Ngai, director of the U.S. National Institutes of Health's BRAIN Initiative. "Without a detailed understanding of how neurons connect with one another, we won't have a basic understanding of what goes right in a healthy brain or what goes wrong in disease."

Neuroscience breakthrough: Research team has mapped the entire brain of an adult fruit fly for the first time

A Princeton-led team of scientists has built the first neuron-by-neuron and synapse-by-synapse roadmap through the brain of an adult fruit fly (Drosophila melanogaster), marking a major milestone in the study of brains. This research is the flagship article in the Oct. 2 special issue of Nature, which is devoted to the new fruit fly "connectome." Previous researchers mapped the brain of a C. elegans worm, with its 302 neurons, and the brain of a larval fruit fly, which had 3,000 neurons, but the adult fruit fly is several orders of magnitude more complex, with almost 140,000 neurons and roughly 50 million synapses connecting them. Fruit flies share 60% of human DNA, and three in four human genetic diseases have a parallel in fruit flies. Understanding the brains of fruit flies is a steppingstone to understanding brains of larger more complex species, like humans. "This is a major achievement," said Mala Murthy, director of the Princeton Neuroscience Institute and, with Sebastian Seung, co-leader of the research team. "There is no other full brain connectome for an adult animal of this complexity." Murthy is also Princeton's Karol and Marnie Marcin '96 Professor of Neuroscience. Princeton's Seung and Murthy are co-senior authors on the flagship paper of the Nature issue, which includes a suite of nine related papers with overlapping sets of authors, led by researchers from Princeton University, the University of Vermont, the University of Cambridge, the University of California-Berkeley, UC-Santa Barbara, Freie Universität-Berlin, and the Max Planck Florida Institute for Neuroscience. The work was funded in part by the NIH's BRAIN Initiative, the Princeton Neuroscience Institute's Bezos Center for Neural Circuit Dynamics and McDonnell Center for Systems Neuroscience, and other public and private neuroscience institutes and funds, listed at the end of this document. The map was developed by the FlyWire Consortium, which is based at Princeton University and made up of teams in more than 76 laboratories with 287 researchers around the world as well as volunteer gamers. Sven Dorkenwald, the lead author on the flagship Nature paper, spearheaded the FlyWire Consortium. "What we built is, in many ways, an atlas," said Dorkenwald, a 2023 Ph.D. graduate of Princeton now at the University of Washington and the Allen Institute for Brain Science. "Just like you wouldn't want to drive to a new place without Google Maps, you don't want to explore the brain without a map. What we have done is build an atlas of the brain, and added annotations for all the businesses, the buildings, the street names. With this, researchers are now equipped to thoughtfully navigate the brain as we try to understand it." And just like a map that traces out every tiny alley as well as every superhighway, the fly connectome shows connections within the fruit fly brain at every scale. The map was built from 21 million images taken of a female fruit fly brain by a team of scientists led by Davi Bock, then at the Howard Hughes Medical Institute's Janelia Research Campus and now at the University of Vermont. Using an AI model built by researchers and software engineers working with Princeton's Sebastian Seung, the lumps and blobs in those images were turned into a labeled, three-dimensional map. Instead of keeping their data confidential, the researchers opened their in-progress neural map to the scientific community from the beginning. "Mapping the whole brain has been made possible by advances in AI computing. It would have not been possible to reconstruct the entire wiring diagram manually. This is a display of how AI can move neuroscience forward,' said Prof. Sebastian Seung, one of the co-leaders of the research and Princeton's Evnin Professor in Neuroscience and a professor of computer science. "Now that we have this brain map, we can close the loop on which neurons relate to which behaviors," said Dorkenwald. The development could lead to tailored treatments to brain diseases. "In many respects, it (the brain) is more powerful than any human-made computer, yet for the most part we still do not understand its underlying logic," said John Ngai, director of the U.S. National Institutes of Health's BRAIN Initiative, which provided partial funding for the FlyWire project. "Without a detailed understanding of how neurons connect with one another, we won't have a basic understanding of what goes right in a healthy brain or what goes wrong in disease."

First Full Brain Map of Adult Fruit Fly Created - Neuroscience News

Summary: Researchers have created the first neuron-by-neuron map of an adult fruit fly brain, marking a major achievement in brain mapping. The map, built using 21 million images, connects nearly 140,000 neurons and 50 million synapses, making it the most complex brain map of any adult animal to date. This "connectome" provides a roadmap for understanding neural circuits and behaviors in more complex species, including humans. The development, powered by AI, opens doors for new insights into brain function and diseases. A Princeton-led team of scientists has built the first neuron-by-neuron and synapse-by-synapse roadmap through the brain of an adult fruit fly (Drosophila melanogaster), marking a major milestone in the study of brains. This research is the flagship article in the Oct. 2 special issue of Nature, which is devoted to the new fruit fly "connectome." Previous researchers mapped the brain of a C. elegans worm, with its 302 neurons, and the brain of a larval fruit fly, which had 3,000 neurons, but the adult fruit fly is several orders of magnitude more complex, with almost 140,000 neurons and roughly 50 million synapses connecting them. Fruit flies share 60% of human DNA, and three in four human genetic diseases have a parallel in fruit flies. Understanding the brains of fruit flies is a steppingstone to understanding brains of larger more complex species, like humans. "This is a major achievement," said Mala Murthy, director of the Princeton Neuroscience Institute and, with Sebastian Seung, co-leader of the research team. "There is no other full brain connectome for an adult animal of this complexity." Murthy is also Princeton's Karol and Marnie Marcin '96 Professor of Neuroscience. Princeton's Seung and Murthy are co-senior authors on the flagship paper of the Nature issue, which includes a suite of nine related papers with overlapping sets of authors, led by researchers from Princeton University, the University of Vermont, the University of Cambridge, the University of California-Berkeley, UC-Santa Barbara, Freie Universität-Berlin, and the Max Planck Florida Institute for Neuroscience. The work was funded in part by the NIH's BRAIN Initiative, the Princeton Neuroscience Institute's Bezos Center for Neural Circuit Dynamics and McDonnell Center for Systems Neuroscience, and other public and private neuroscience institutes and funds, listed at the end of this document. The map was developed by the FlyWire Consortium, which is based at Princeton University and made up of teams in more than 76 laboratories with 287 researchers around the world as well as volunteer gamers. Sven Dorkenwald, the lead author on the flagship Nature paper, spearheaded the FlyWire Consortium. "What we built is, in many ways, an atlas," said Dorkenwald, a 2023 Ph.D. graduate of Princeton now at the University of Washington and the Allen Institute for Brain Science. "Just like you wouldn't want to drive to a new place without Google Maps, you don't want to explore the brain without a map. What we have done is build an atlas of the brain, and added annotations for all the businesses, the buildings, the street names. With this, researchers are now equipped to thoughtfully navigate the brain as we try to understand it." And just like a map that traces out every tiny alley as well as every superhighway, the fly connectome shows connections within the fruit fly brain at every scale. The map was built from 21 million images taken of a female fruit fly brain by a team of scientists led by Davi Bock, then at the Howard Hughes Medical Institute's Janelia Research Campus and now at the University of Vermont. Using an AI model built by researchers and software engineers working with Princeton's Sebastian Seung, the lumps and blobs in those images were turned into a labeled, three-dimensional map. Instead of keeping their data confidential, the researchers opened their in-progress neural map to the scientific community from the beginning. "Mapping the whole brain has been made possible by advances in AI computing. It would have not been possible to reconstruct the entire wiring diagram manually. This is a display of how AI can move neuroscience forward,' said Prof. Sebastian Seung, one of the co-leaders of the research and Princeton's Evnin Professor in Neuroscience and a professor of computer science. "Now that we have this brain map, we can close the loop on which neurons relate to which behaviors," said Dorkenwald. The development could lead to tailored treatments to brain diseases. "In many respects, it (the brain) is more powerful than any human-made computer, yet for the most part we still do not understand its underlying logic," said John Ngai, director of the U.S. National Institutes of Health's BRAIN Initiative, which provided partial funding for the FlyWire project. "Without a detailed understanding of how neurons connect with one another, we won't have a basic understanding of what goes right in a healthy brain or what goes wrong in disease." Funding: This research was supported by the National Institutes of Health (NIH) BRAIN Initiative (RF1 MH117815, RF1 MH129268, 1RF1MH120679-01 and U24 NS126935) and National Institute Of Neurological Disorders And Stroke (NINDS) (RF1NS121911); the Princeton Neuroscience Institute's Bezos Center for Neural Circuit Dynamics and McDonnell Center for Systems Neuroscience; Google; the Allen Institute for Brain Science; the National Science Foundation (NSF Neuronex2 2014862, Neuronex2 MRC MC_EX_MR/T046279/1, MRC MC-U105188491, PHY-1734030); Wellcome Trust Collaborative Award (203261/Z/16/Z and 220343/Z/20/Z); a Marie Skłodowska-Curie postdoctoral fellowship (H2020-WF-01-2018-867459); the Portuguese Research Council (Grant PTDC/MED-NEU/4001/2021); and the Intelligence Advanced Research Projects Activity (IARPA) via the Department of Interior (DOI) (D16PC0005). Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 10 chemical synapses between 139,255 neurons reconstructed from an adult female Drosophila melanogaster. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome -- a map of projections between regions -- from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Researchers unveil complete neuronal map of fruit fly brain

By Dr. Chinta SidharthanReviewed by Benedette Cuffari, M.Sc.Oct 4 2024 The study offers valuable insights into how sensory cues are processed and information moves through the neuronal network, opening new pathways to a deeper understanding of the mammalian brain. Study: Neuronal wiring diagram of an adult brain. Image Credit: vitstudio / Shutterstock.com In a recent study published in Nature, researchers map the whole brain of Drosophila melanogaster, or the fruit fly, which comprises about 140,000 neurons and over 50 million synapses.Advancements in mapping the brain Brains are vital for the evolution of complex behaviors; however, technological limitations have prevented scientists from mapping the connections within and between different regions of the brain at the neuronal and synaptic levels. Nevertheless, rapid advancements in imaging techniques like electron microscopic brain imaging have allowed scientists to create detailed wiring diagrams of animal brains. Recent neurobiological studies on Drosophila melanogaster or fruit flies have identified over 100,000 neurons and about 100 million synapses involved in the control of movement, vision, and social interactions in the brain. These observations have provided important insights into various behaviors in fruit flies such as navigation, sensory processing, and memory, providing valuable insights into the mammalian brain. About the study The present study was conducted by a large team of researchers including various scientists from Princeton University and The FlyWire Consortium. The FlyWire Consortium is a large group of neurobiologists, proofreaders, and computer scientists using artificial intelligence and imaging tools to build and curate the first Drosophila whole-brain connectome. These researchers expanded current knowledge of the adult Drosophila melanogaster brain by presenting a complete diagram of the neuronal wiring of the brain of a female adult fruit fly. Various advanced methods were utilized to analyze brain data, including electron microscopy imaging of one-week-old female fruit flies and neural networks to align images and segment the cells. Previous brain models were used to segment neuropils, which are synapse-dense regions in the brain. The volume of each neuropil was calculated and neuropils were classified into different brain regions. Synapses were then assigned to neuropils based on their locations. Any synapses that could not be matched to the exact neuropil were assigned to the nearest one within 10 micrometers. The neuron segmentation was then reviewed and corrected by proofreaders to ensure data accuracy. Machine learning tools were also used to predict the types of synapses and identities of neurotransmitters. To ensure that data was complete, proofreading was focused on neurons in the central brain with large synapse counts and visible nuclei. Neurons that underwent significant changes in the proofreading process were flagged for further review to ensure a thorough correction process. Citizen scientists also contributed to annotating and categorizing neurons based on their connectivity and function. Various machine learning tools were then used to predict the neurotransmitter type at each synapse to understand communication pathways within the fruit fly brain. Study findings The researchers identified the connectome, which is a complete map of the adult female Drosophila melanogaster brain. A total of 139,255 neurons and 54.5 million synapses were identified, which provides valuable insights into the connections and communication between neurons. This collaborative effort identified 8,400 cell types in the connectome, which is accessible through The FlyWire Consortium's connectome data explorer. These findings also highlight important parts of the fruit fly brain, including the suboesophageal zone, which processes sensory data, as well as the optic lobes involved in vision. The researchers also elucidated how neurons connect to the ventral nerve cord, which controls movement. Furthermore, the brain map provides a comprehensive image of the neurons involved in taste and touch. The manual checks through proofreading ensured a 99.2% accuracy in the correct mapping of neurons. The current study also offers a novel method to study the flow of information in neuronal networks by ranking neurons based on their speed in processing sensory inputs. Conclusions The current study endeavor was a significant advancement as compared to previous efforts to map the brains of Drosophila larvae and the nematode Caenorhabditis elegans. Through the comprehensive neuronal map or connectome of the adult Drosophila brain, the researchers discovered novel pathways involved in the connectivity, communication, and functions of neurons within the brain. The study findings provide critical insights into the processing of sensory cues and flow of information through the neuronal network, thereby paving the way toward a better understanding of the mammalian brain. Journal reference: Dorkenwald, S., Matsliah, A., Sterling, A. R., et al. (2024). Neuronal wiring diagram of an adult brain. Nature 124-138. doi:10.1038/s41586-024-07558-y

Tiny brain, big deal: fruit fly diagram could transform neuroscience

Scientists took years to map 50m connections, which may lead to understanding of how wiring gives rise to behaviour Researchers have produced the first wiring diagram for the whole brain of a fruit fly, a feat that promises to revolutionise the field of neuroscience and pave the way for unprecedented insights into how the brain produces behaviour. Rarely in science has so much effort been directed toward so little material, with scientists taking years to map the meanderings of all 139,255 neurons and the 50m connections bundled up inside the fly's poppy seed-sized brain. In the process, the researchers classified more than 8,400 different cell types, amounting to the first complete parts list for building a fly brain. "You might be asking why we should care about the brain of a fruit fly," said Sebastian Seung, a professor of computer science and neuroscience at Princeton University and a co-leader on the FlyWire project. "My simple answer is that if we can truly understand how any brain functions, it's bound to tell us something about all brains." The intricate tangle of neurons, which if unravelled would reach for 150 metres, was mapped out through a painstaking process that started with slicing a female fruit fly brain into 7,000 thin slivers. Each section was imaged in an electron microscope to reveal structures as small as four-millionths of a millimetre wide. The researchers then turned to artificial intelligence (AI) to analyse the millions of images and trace the path of every neuron and synaptic connection throughout the minuscule organ. Because the AI made plenty of mistakes, a global army of scientists and volunteers was recruited to help correct the errors and finalise the map. The work has already borne fruit. Armed with the diagram, researchers have discovered "interrogator" neurons that appear to combine diverse types of information, and "broadcasters" that may send out signals to coordinate activity across different neural circuits. A specific neural circuit that, when triggered, causes fruit flies to stop in their tracks while walking, was also spotted. In a foretaste of what is to come, researchers used the wiring diagram, known as the connectome, to build a computer simulation of part of the fly brain. Experiments with the simulation led them to identify neural circuits used to process taste, suggesting that future simulations can shed further light on how brain wiring gives rise to animal behaviour. "Connectomics is the beginning of a digital transformation of neuroscience ... and this transformation will extend to brain simulation," Seung said. "This is going to be a rapid acceleration of the way in which we do neuroscience." Details of the project, which involved researchers from Canada, Germany and the MRC Laboratory of Molecular Biology and the University of Cambridge in the UK, are published across nine papers in Nature. In an accompanying article, Dr Anita Devineni, a neuroscientist at Emory University in Atlanta, called the wiring diagram a "landmark achievement". Work has already begun to produce a complete wiring diagram for the mouse brain, which researchers hope to complete in five to 10 years. But repeating the feat for a whole human brain, with its 86bn neurons and trillions of connections, is another question. The human brain is roughly a million times more complex than the fruit fly brain, putting a complete wiring diagram beyond practical reach with today's technology. It would also require some hefty memory: scientists estimate it would amount to a zettabyte of data, equivalent to all of the world's internet traffic for a year. A more realistic approach is to map neuronal wiring in parts of the human brain, research that could ultimately shed light on whether miswiring underpins neuropsychiatric and other brain disorders. "Simply put, we cannot fix what we do not understand and this is the basis of why we believe this is such an important moment today," said Dr John Ngai, the director of the US National Institutes of Health's Brain Initiative.

Largest Brain Map Ever Reveals Fruit Fly's Neurons in Exquisite Detail

Wiring diagram lays out connections between nearly 140,000 neurons and reveals new types of nerve cell A fruit fly might not be the smartest organism, but scientists can still learn a lot from its brain. Researchers are hoping to do that now that they have a new map -- the most complete for any organism so far -- of the brain of a single fruit fly (Drosophila melanogaster). The wiring diagram, or 'connectome', includes nearly 140,000 neurons and captures more than 54.5 million synapses, which are the connections between nerve cells. "This is a huge deal," says Clay Reid, a neurobiologist at the Allen Institute for Brain Science in Seattle, Washington, who was not involved in the project but has worked with one of the team members who was. "It's something that the world has been anxiously waiting for, for a long time." The map is described in a package of nine papers about the data published in Nature today. Its creators are part of a consortium known as FlyWire, co-led by neuroscientists Mala Murthy and Sebastian Seung at Princeton University in New Jersey. If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. Seung and Murthy say that they've been developing the FlyWire map for more than four years, using electron microscopy images of slices of the fly's brain. The researchers and their colleagues stitched the data together to form a full map of the brain with the help of artificial-intelligence (AI) tools. But these tools aren't perfect, and the wiring diagram needed to be checked for errors. The scientists spent a great deal of time manually proofreading the data -- so much time that they invited volunteers to help. In all, the consortium members and the volunteers made more than 3 million manual edits, according to co-author Gregory Jefferis, a neuroscientist at the University of Cambridge, UK. (He notes that much of this work took place in 2020, when fly researchers were at loose ends and working from home during the COVID-19 pandemic.) But the work wasn't finished: the map still had to be annotated, a process in which the researchers and volunteers labelled each neuron as a particular cell type. Jefferis compares the task to assessing satellite images: AI software might be trained to recognize lakes or roads in such images, but humans would have to check the results and name the specific lakes or roads themselves. All told, the researchers identified 8,453 types of neuron -- much more than anyone had expected. Of these, 4,581 were newly discovered, which will create new research directions, Seung says. "Every one of those cell types is a question," he adds. The team was surprised by some of the ways in which the various cells connect to one another, too. For instance, neurons that were thought to be involved in just one sensory wiring circuit, such as a visual pathway, tended to receive cues from multiple senses, including hearing and touch. "It's astounding how interconnected the brain is," Murthy says. The FlyWire map data have been available for the past few years for researchers to explore. This has enabled scientists to learn more about the brain and about fruit flies -- findings that are captured in some of the papers published in Nature today. In one paper, for example, researchers used the connectome to create a computer model of the entire fruit-fly brain, including all the connections between neurons. They tested it by activating neurons that they knew either sense sweet or bitter tastes. These neurons then launched a cascade of signals through the virtual fly's brain, ultimately triggering motor neurons tied to the fly's proboscis -- the equivalent of the mammalian tongue. When the sweet circuit was activated, a signal for extending the proboscis was transmitted, as if the insect was preparing to feed; when the bitter circuit was activated, this signal was inhibited. To validate these findings, the team activated the same neurons in a real fruit fly. The researchers learnt that the simulation was more than 90% accurate at predicting which neurons would respond and therefore how the fly would behave. In another study, researchers describe two wiring circuits that signal a fly to stop walking. One of these contains two neurons that are responsible for halting 'walk' signals sent from the brain when the fly wants to stop and feed. The other circuit includes neurons in the nerve cord, which receives and processes signals from the brain. These cells create resistance in the fly's leg joints, allowing the insect to stop while it grooms itself. One limitation of the new connectome is that it was created from a single female fruit fly. Although fruit-fly brains are similar to each other, they are not identical. Until now, the most complete connectome for a fruit-fly brain was a map of a 'hemibrain' -- a portion of a fly's brain containing around 25,000 neurons. In one of the Nature papers out today, Jefferis, Davi Bock, a neurobiologist at the University of Vermont in Burlington, and their colleagues compared the FlyWire brain with the hemibrain. Some of the differences were striking. The FlyWire fly had almost twice as many neurons in a brain structure called the mushroom body, which is involved in smell, compared with the fly used in the hemibrain-mapping project. Bock thinks the discrepancy could be because the hemibrain fly might have starved while it was still growing, which harmed its brain development. The FlyWire researchers say that much work remains to be done to fully understand the fruit-fly brain. For instance, the latest connectome shows only how neurons connect through chemical synapses, across which molecules called neurotransmitters send information. It doesn't offer any information about electrical connectivity between neurons or about how neurons chemically communicate outside synapses. And Murthy hopes to eventually have a male fly connectome, too, which would allow researchers to study male-specific behaviours such as singing. "We're not done, but it's a big step," Bock says.

So Fly: Scientists Complete Map of Adult Fruit Fly Brain

WEDNESDAY, Oct. 2, 2024 (HealthDay News) -- The head of a Princeton team that mapped the brain of an adult fruit fly -- a watershed step in understanding the human brain -- explains the feat in a way that belies its complexity. "Just like you wouldn't want to drive to a new place without Google Maps, you don't want to explore the brain without a map," explained lead author Sven Dorkenwald, who received his Ph.D. last year from Princeton and is now at the Allen Institute for Brain Science in Seattle. "What we have done is build an atlas of the brain, and added annotations for all the businesses, the buildings, the street names." With this, he added in a Princeton news release, "researchers are now equipped to thoughtfully navigate the brain as we try to understand it." Likening it to a roadmap that traces every tiny alley as well as every superhighway, he said the new map -- called a "connectome" -- shows connections in the fruit fly brain at every scale. It could one day lead to tailored treatments for brain diseases. Researchers described their work Oct. 2 in a special issue of the journal Nature. They created a neuron-by-neuron and synapse-by-synapse map of the brain of an adult fruit fly (Drosophila melanogaster). It identifies different types of neurons and chemical links -- or synapses -- between them and offers information about the type of chemicals secreted by each neuron. Fruit flies share 60% of human DNA, and have a parallel to 3 in 4 human genetic diseases. Understanding their brains is a step toward understanding those of more complex species, including people, the researchers said. The fruit fly is also deep thinker, able to form long-term memories, engage in social interactions and navigate over large distances. Now that its connectome has been established, researchers hope to use the same methods to map larger-brained animals. "This is a major achievement," said study co-leader Mala Murthy, director of the Princeton Neuroscience Institute. "There is no other full brain connectome for an adult animal of this complexity." Other researchers had already mapped the brains of a C. elegans worm and a larval fruit fly, which had 302 and 3,000 neurons, respectively. The brain of an adult fruit fly is far more complex, boasting nearly 140,000 neurons linked by an estimated 50 million synapses. John Ngai, director of the National Institute of Health's Brain Research Through Advancing Innovative Neurotechnologies Initiative (BRAIN), hailed the achievement. "The diminutive fruit fly is surprisingly sophisticated and has long served as a powerful model for understanding the biological underpinnings of behavior," he said in an NIH news release. "This milestone not only provides researchers a new set of tools for understanding how the circuits in the brain drive behavior, but importantly serves as a forerunner to ongoing BRAIN-funded efforts to map the connections of larger mammalian and human brains." In a companion paper also published in Nature, researchers reported on creating a separate map, known as a projectome, of projections between brain regions. The projectome allows for detailed mapping of specific brain circuits that control behavior, such as the ocellar brain circuit, they said. It takes in visual stimuli and orients the fly during flight. To create the maps, researchers from the Princeton-based FlyWire Consortium, which includes 287 researchers in more than 76 labs worldwide, used an AI model and 21 million brain images. The AI model turned "lumps and blobs" in those images into a labeled three-dimensional map. Researchers shared their work with the broader scientific community as they worked. "It would not have been possible to reconstruct the entire wiring diagram manually," noted project co-leader Sebastian Seung, a professor of neuroscience and computer science at Princeton. "This is a display of how AI can move neuroscience forward." The NIH's BRAIN Initiative provided partial funding for the project. "In many respects, [the brain] is more powerful than any human-made computer, yet for the most part we do not understand its underlying logic," Ngai said. "Without a detailed understanding of how neurons connect with one another, we won't have a basic understanding of what goes right in a healthy brain or what goes wrong in a disease." More information The Society for Brain Mapping & Therapeutics explains how brain mapping help researchers understand the brain and its applications for human health.

Creating the largest, most comprehensive picture of neural connections to date

Flip a switch on the wall, and it turns on a light across the room through a simple circuit. Now add 140,000 other switches and try and figure out which one controls the light. That is similar to the challenge undertaken by an international consortium of researchers who have worked to map all of the connections in the brain of an adult fruit fly. The map, known as a connectome, will aid in understanding the inner workings of the brain and how it controls behavior and is already spurring new experiments and models. Fruit flies may be very small, but mapping their brain is no easy task. There are on the order of 140,000 neurons and over 8,000 cell types identified in the newly published connectome. The research team used automation and artificial intelligence to piece together the connections from data created using electron microscopy. This connectome is the largest created to date, with some of the same researchers previously publishing a map of a larval fruit fly brain that was at the time the largest connectome created. The new research, published as part of a package of related articles in Nature, was co-authored by the FlyWire Consortium, which brought together hundreds of scientists from across the globe to collaborate on linking neuronal wiring with brain function. Part of the consortium included members of the NSF NeuroNex international network Enabling Identification and Impact of Synaptic Weight in Functional Networks. "NeuroNex has brought together researchers across disciplines and continents, linking them with access to innovative tools and resources, and providing conceptual foundations so they can ask questions about how the brain works in a variety of species and discover general principles," said Edda Thiels, a program director in the NSF Directorate for Biological Sciences. "These large teams were a key component of the program and have helped to answer grand challenges in neuroscience and society."

Complete map of fruit fly brain circuitry unveiled

AI tools and hundreds of human proofreaders helped tease apart 140,000 neurons in a brain the size of a grain of sand How do electrical impulses traveling among a tangle of neurons drive complex behaviors? Researchers seeking the answer have reconstructed the complete wiring diagram, or connectome, of the fruit fly's adult brain -- a feat akin to mapping all the buildings, avenues, and streets in a complex city. The comprehensive map will advance research on the neural activity that underlies fundamental processes such as walking and seeing in Drosophila melanogaster, an insect species widely used as a model organism. Neuroscientists are hailing this achievement, published today in a nine-paper package in , as a milestone that will boost other, more ambitious connectome projects in zebrafish, mice, and even humans. When scientist complete an animal's connectome -- a feat first achieved for the nematode Caenorhabditis elegans decades ago -- "suddenly, the level of understanding is miles away from anything before," says Albert Cardona, a circuit neuroscientist at the Medical Research Council Laboratory of Molecular Biology who was not involved in the project. "There is a before and after connectome -- B.C. and A.C.," he says, referencing a well-known quote from Columbia University theoretical neuroscientist Larry Abbott. Cardona says researchers can now finally make sense of how basic functions such as vision and olfaction work in the fly, as well as probe more complex behaviors such as navigation and decision-making. "It's the end of the beginning" for fly neuroscientists, he says. Since the publication of C. elegans's 302-neuron connectome in 1986, researchers have created partial connectomes for fly, mouse, and human brains. Cardona and his team published the connectome of D. melanogaster larva last year. But this is the first complete connectome of an adult organism in decades. The effort started in 2018 when researchers at the Howard Hughes Medical Institute's Janelia Research Campus imaged a female fly's brain at nanometer resolution using electron microscopy and made it publicly available. Fly neuroscientist Mala Murthy and computational neuroscientist Sebastian Seung at the Princeton Neuroscience Institute had the idea to use those images to identify and map the connections between each visible neuron, creating a connectome. "But it seemed really ridiculous," Murthy says. "It was just too big a product. Nobody had made a map at that scale." A kind of artificial intelligence (AI) known as machine learning can help turn imaging data into 3D reconstructions of each neuron and its synapses, the connections with other neurons. But the algorithms powering it make mistakes, so the reconstructions need to be corrected by hand. To achieve the feat, Murthy and Seung formed the FlyWire Consortium, a group of labs mainly in the Unites States and Europe funded in part by the U.S. National Institutes of Health's Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. They built an online platform in 2022 to allow hundreds of nonexpert volunteers to manually proofread the reconstructions and classify each neuron. The task would have taken a single person 33 years working alone, the group estimates. "This kind of data sharing is ... unprecedented," Murthy says. The final map charts 149 meters of wiring packed in a brain the size of a grain of sand. It also includes 54.5 million synapses among about 140,000 neurons, which the team classified into more than 8400 types, many of which are newly identified. "This achievement is not just remarkable, it's outstanding," says Moritz Helmstaedter, a neuroscientist at the Max Planck Institute for Brain Research who was not involved in the project. The connectome's completeness, he adds, is key: Researchers who discover interesting behavior in fly experiments can now look to the connectome for its underpinnings. "There's a fence around this," he says of the data set, "and there is no explanation [of wiring possibilities] outside of this garden of beautiful neurons." In other papers in the package, researchers give a glimpse of how the fly connectome can be used to answer research questions. For example, one team was able to pinpoint two different neural circuits the fly uses to stop walking in distinct contexts -- when it halts during feeding, and when it pauses to groom itself. Another team used the data to create a computational model that correctly predicted which neurons sense sugar or water. In a third study, Seung predicted which neurons are part of a circuit important for vision based on the wiring of the fly's optic lobe. Because FlyWire has made the project data public from its inception, the connectome has already been used in more than 50 publications. "Sometimes, when you do something in science, nobody pays attention. But sometimes, people not only pay attention -- they actually use it for their own research and they're grateful," Seung says. "That's a very nice feeling." The resource has been transformative for Emory University neuroscientist Anita Devineni, who wrote a commentary accompanying the new papers and whose team has used the connectome to analyze fly taste circuits. "For decades, we haven't known what the taste neurons in the brain are," she says, "And then, all of a sudden in a small amount of time ... you can figure it out." She hopes FlyWire's scientific yield will reassure funders that investing in connectomes pays off. (The BRAIN Initiative's budget was cut by 40% this year, she notes.) Researchers can now compare this snapshot of an adult fly brain with the larva connectome to answer questions about what changes during neural development. And to examine sex differences, Murthy and others are working on reconstructing the connectome of a male fly brain, as well as an even more complete connectome that includes the fly's nerve cord. Researchers predict the technology developed for FlyWire -- in particular, the integration of AI with crowdsourcing for proofreading -- will help speed similar projects. The zebrafish connectome is expected to be finished in the next few years. And Helmstaedter predicts mouse and human brains (with approximately 500 and 600,000 times more neurons, respectively, than the fly's) could come after that: "In the next decade, we'll see tremendous progress, and possibly the first full whole mammalian brain connectome."

First map of adult insect's brain offers clues on neurological diseases

An international scientific team has built the first map of an adult insect's brain, offering a potential breakthrough for our understanding of how the organ works and why it is harmed by neurological diseases. The project plotted the full 149 metres of biological wiring that make up a fruit fly's poppy seed-sized brain and govern the organism's life. It promises to boost knowledge of the human brain since the two species' organs share many common features, including genes linked to neurological conditions that afflict billions of people worldwide. "One of the major questions we're addressing is how the wiring of the brain, its neurons and connections can give rise to animal behaviour," said Mala Murthy, co-lead of the FlyWire research consortium and a professor of neuroscience at Princeton University. "Flies are an important model system for neuroscience, since their brains solve many of the same problems we do." The venture, published in Nature on Wednesday, had parallels to the Human Genome Project, which was concluded in 2003, researchers said. That sequencing mission has helped power many discoveries about disease. FlyWire aimed to chart a "connectome" -- a set of possible pathways for information to flow between the neuron cells that make up the brain and the synapses linking them. Researchers sliced up the brain of the Drosophila fruit fly into more than 7,000 sections, analysed them using powerful microscopes and rendered the results as a 3D image. The raw diagram was then annotated to identify thousands of different characteristic cell types, in what one scientist described as like adding features such as street names and business opening hours to a Google map. The project used crowdsourcing to assemble "citizen scientists" to ease a proof-reading burden that would have taken one person an estimated 33 years to complete. The resulting Drosophila connectome of about 140,000 neurons and 50mn synaptic connections is available to researchers for free online. Scientists have already begun looking at how the parts of the brain structure might relate to functions such as walking, tasting and seeing. "If we can truly understand how any brain functions, it's bound to tell us something about all brains," said Sebastian Seung, another co-author on the Nature papers and a Princeton professor. "It's fair to say that this past decade has seen revolutionary progress in understanding the fly brain." The connectome offers a "ground truth" that could help power research into neurological diseases, said John Ngai, a co-author and director of the BRAIN initiative at the US National Institutes of Health. More than 40 per cent of the global population suffered nervous system problems such as stroke, dementia and migraine in 2021, according to research published in March. "Having this map in hand is necessary -- but not sufficient," Ngai said. "It will really allow us to ask better questions and more precise questions." A separate project has begun to map the brain of a mouse, estimated to be a million times larger than that of a baby fruit fly's. The human brain represents an even tougher challenge: it contains more than 80bn neurons and 100tn connections. The genome analogy suggests how future work on brain structures could overcome FlyWire's limitations, such as its lack of data on non-synaptic ways neurons communicate, said Anita Devineni, an Emory University assistant professor. As with the genome work, development of better brain maps will drive progress in areas such as artificial intelligence algorithms. In a commentary published in Nature, Devineni said FlyWire had "driven technological and conceptual advances that will facilitate the reconstruction and interpretation of future connectomes in Drosophila and other species".