Scientists have developed the most comprehensive and detailed brain connectivity map of a mammal so far, focusing on a tiny cubic millimeter of mouse brain tissue. This groundbreaking work not only charts the cells but also tracks the functioning of individual neurons across a large network—a pioneering feat in neuroscience.

This intricate 3D map includes over 200,000 brain cells, with approximately 82,000 being neurons. It features over 500 million synaptic connections and over 4 kilometers of neural pathways, all within a minuscule section of brain tissue responsible for vision. This is only rivaled in scale by a similar cubic millimeter mapping of the human brain, which comprised 16,000 neurons and 150 million synapses. Additionally, this new map has successfully captured the activities of tens of thousands of neurons as they transmit signals and interact during the visual processing.

The integration of this brain-activity map with the neural wiring diagram represents a significant milestone in connectomics—the study aimed at illustrating how brains manage and structure information. Over 150 researchers involved in the Machine Intelligence from Cortical Networks (MICrONS) project, have shared this feat in a series of eight research papers published today in Nature and Nature Methods. The MICrONS project has also made its findings accessible online for the neuroscience community, with various teams already utilizing this data in their research.

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“What they’ve achieved is something unprecedented in the history of neuroscience: mapping neuron activity onto their connections across a massive network of neurons,” says Mariela Petkova, a neuroscientist at Harvard University in Cambridge, Massachusetts, who is not part of the project. “This is something we’ve never observed on this scale before.”

“The data are absolutely strikingly beautiful,” remarks Forrest Collman, a neuroscientist at the Allen Institute for Brain Science in Seattle, Washington, and co-author of the studies. “It really makes you marvel at the complexity of the brain, much like gazing at the stars in the night sky.”

A Mouse’s Brain Exposed

To create this innovative map, researchers first monitored the firing of almost 76,000 neurons in the visual cortex of a mouse while it viewed various videos, including scenes from The Matrix, over two hours. They then meticulously sliced a cubic millimeter of the mouse’s brain into thousands of ultra-thin sections, each roughly one four-hundredth the thickness of a human hair.

The researchers then imaged each slice and compiled these images into a three-dimensional map. Advanced artificial intelligence and machine learning algorithms were employed to annotate the neurons, their branching structures, and their synapses. The team also correlated these mapped neurons with their earlier recordings of active brain cells.

Moritz Helmstaedter, a neuroscientist at the Max Planck Institute for Brain Research in Frankfurt, Germany, describes the combination of function and structure at this scale as unprecedented. “It’s a truly impressive endeavor and a remarkable success,” he notes.

Linking Firing and Wiring

The research provides new insights into the fundamental principles that govern neural circuits in the mouse brain. It was noted that neurons in the cortex that react to similar visual stimuli—like specific shapes or movement directions—tend to connect more frequently with each other, regardless of their physical distance, compared to neurons that respond to different stimuli.

This finding adds a new dimension to a longstanding theory in neuroscience, Collman explains, the idea that “neurons that fire together wire together.” While previous studies have explored this concept, they did so with far fewer neurons and synapses. This latest study demonstrates the varied application of this rule across different aspects of the cortex, he adds.

The MICrONS researchers are hopeful that their dataset will help uncover more about the brain’s features and functions. “There are many cortical areas that we understand in varying levels of detail and from different perspectives. And I believe this is just the beginning of correlating structure with function,” states Clay Reid, a neurobiologist at the Allen Institute and co-author of the MICrONS papers.

Helmstaedter believes the wiring maps could be used to investigate how the brain stores and retrieves visual memories, such as “our memories of the last birthday party or of our grandparents.” These remain “the big unresolved questions about the mammalian cortex that are still very fundamental,” he concludes.

This article is reproduced with permission and was first published on April 9, 2025..