WASHINGTON — Scientists have achieved a milestone in brain mapping, thanks to a mouse watching clips from “The Matrix.” They have developed the most extensive functional map of a brain ever assembled, diagramming the intricate connections of 84,000 neurons as they transmit signals.
Utilizing a fragment of the mouse’s brain approximately the size of a poppy seed, researchers identified the neurons and charted their communication paths through an astounding 500 million synaptic junctions. These synapses facilitate the transmission of messages between neurons through branch-like fibers. This substantial dataset, revealed in the journal Nature, represents a significant stride towards deciphering the complexities of brain function. Through a vivid 3D reconstruction that distinguishes various brain circuits, the data has been made available for scientists globally to further probe or for curious minds to explore.
“It definitely inspires a sense of awe, just like looking at pictures of the galaxies,” commented Forrest Collman from the Allen Institute for Brain Science in Seattle, one of the project’s main researchers. He added, “You get a sense of how complicated you are. We’re looking at one tiny part … of a mouse’s brain and the beauty and complexity that you can see in these actual neurons and the hundreds of millions of connections between them.”
Neurons, or nerve cells, are pivotal to how we think, feel, see, communicate, and move as they activate and send signals to each other. Scientists have long understood that these signals traverse from one neuron through axons and dendrites, using synapses to leap to another neuron. However, much about the specific networks of neurons responsible for distinct functions and how alterations in these networks might contribute to disorders like Alzheimer’s or autism remains unexplored.
“You can make a thousand hypotheses about how brain cells might do their job but you can’t test those hypotheses unless you know perhaps the most fundamental thing – how are those cells wired together,” stated Clay Reid, a scientist at the Allen Institute who has pioneered the use of electron microscopy to investigate neural connections.
In this venture, a worldwide team of over 150 researchers mapped neural connections, which Collman likens to tangled spaghetti threads; these threads navigate the region of the mouse brain related to vision. The experiment commenced with showing a mouse short clips of science fiction films, sports events, animations, and nature scenes.
A group at Baylor College of Medicine led this phase, working with a genetically engineered mouse whose neurons glow when active. A laser-powered microscope captured how specific cells in the mouse’s visual cortex illuminated in response to the presented images. Researchers at the Allen Institute then examined a small brain tissue section from the mouse, slicing it into over 25,000 layers — each thinner than a human hair. They created nearly 100 million high-resolution images of these slices using electron microscopy, revealing spaghetti-like fibers and meticulously reconstructing the data in 3D form.
Princeton University scientists took over to apply artificial intelligence to track these connections, painstakingly color-coding individual wires to differentiate them. “The technology developed by this project will give us our first chance to really identify some kind of abnormal pattern of connectivity that gives rise to a disorder,” said Sebastian Seung, a leading researcher and neuroscientist. They estimated that if laid straight, the microscopic wiring would extend more than three miles (5 kilometers). Importantly, they managed to correlate this anatomy with the activity evident in the mouse’s brain while watching the movies, aiding researchers in tracing circuit operations.
Princeton researchers also produced digital 3D replicas of the data for other scientists to employ in new studies. While this endeavor sets the foundational stage for potential treatments of brain disorders, it is likened to the early stages of the Human Genome Project, which gradually inspired gene-based medical advancements. A future aim is to map a complete mouse brain.
Harvard neuroscientists Mariela Petkova and Gregor Schuhknecht, uninvolved in the project, praised the work, describing it as “a major leap forwards and [offering] an invaluable community resource for future discoveries.” They believe this vast and openly shared data will assist in deciphering the complex neural networks that dictate cognitive and behavioral functions. Financed by the National Institutes of Health’s BRAIN Initiative and IARPA, the Intelligence Advanced Research Projects Activity, the Machine Intelligence from Cortical Networks, or MICrONS consortium, facilitated this groundbreaking research.