A brain particle, a universe of connections – the first 3D map that challenges science

Using a particle from a mouse brain, the size of a grain of sand, scientists have created the first accurate, three-dimensional map of a mammal's brain.

This map describes in detail the shape, function and activity of 84 neurons – branched structures that transmit messages through a long “arm” called an axon and then through more than 500 million ‘synapses’, and includes 200 other brain cells.

The small piece of tissue contained 5.4 kilometers of neuronal connections – almost one and a half times the length of Central Park in New York.

This paper is the culmination of nearly a decade of research by 150 scientists at 22 institutions, led by the Allen Institute for Brain Science, Baylor College of Medicine and Princeton University, writes cnn.

“One of the side effects of this project is that it shows us how incredibly beautiful the brain is,” said Dr. Forrest Collman, associate director for data and technology at the Allen Institute, in a video released by the organization.

"Just by looking at these neurons, you can see their detail and size in a way that makes you appreciate the brain with a sense of wonder, just like when you look at a photograph of a galaxy far, far away," he added.

This remarkable map represents only 1/500 of the full volume of a mouse brain, yet the team ended up with 1.6 petabytes of data – a staggering amount that equates to 22 years of uninterrupted HD video.

The project, known as Machine Intelligence from Cortical Networks (MICrONS), has made this data public.

The researchers describe this work in several articles published in the journal Nature on April 9.

Building brain activity

To build the map, scientists at Baylor College of Medicine in Houston, USA, began by using specialized microscopes to record brain activity in a 1 cubic millimeter piece of tissue in the visual cortex of a laboratory mouse — where the animal processes what it sees — over several days.

The researchers ensured that the mice were awake and receiving visual stimuli during the imaging by having them run on a treadmill and watch 10-second clips from various movies, including “The Matrix” and “Mad Max: Fury Road.” According to a statement from Princeton University, YouTube clips of extreme sports such as motocross, luge and BASE jumping were also part of the video rotation.

Then, after the mouse was euthanized, researchers from the Allen Institute in Seattle took the same cubic millimeter of brain and sliced ​​it into more than 28 layers, each 1/400th the thickness of a human hair, taking pictures of each layer as they went. They then reconstructed the images into a single composite.

"This took us about 12 days and 12 nights with the team working in shifts 24 hours a day; not because we were cutting them by hand, but it was an automatic machine," said Dr. Nuno Maçarico da Costa, a research associate at the Allen Institute.

"We had to be there to stop the car at any moment if we thought we were going to lose more than one piece in a row. If that happened," da Costa said, "the experiment would have to start over, adding that the whole process was very stressful."

A team in Princeton University in New Jersey then used machine learning and artificial intelligence tools to track each neuron through the layers of tissue, coloring the neurons so that they lit up individually — a process called segmentation. The information generated by the artificial intelligence is checked and verified by the scientists involved, a process that is still ongoing.

This work culminated in a unified view of what scientists call the mouse brain's "connectome" — a map that shows how certain parts of the mouse brain are organized and provides insights into how different cell types work together.

“The connectome is the beginning of the digital transformation of brain science,” said Dr. Sebastian Seung, Evnin Professor of Neuroscience at Princeton University and professor of computer science.

"With just a few keystrokes, you can search for information and get results within seconds. Some of that data once required an entire doctoral thesis to collect. And that's the power of digital transformation," he said in a press release.

Impossible challenge?

Mapping the brain in this way has long been considered an impossible challenge. Molecular biologist Francis Crick, winner of the Nobel Prize for describing the structure of DNA, had suggested that neuroscientists would never be able to achieve such a detailed understanding of the brain.

"There is no point in asking for the impossible, such as the exact wiring diagram for a cubic millimeter of brain tissue and how all its neurons are activated," he wrote in Scientific American magazine in 1979.

The mouse brain's "connectome" builds on similar work done on even smaller creatures: the worm's connectome. nematode C. elegans was completed in 2019, and scientists published a map of all the neurons in the brain of fruit fly in 2024.

A cubic millimeter of a mouse brain is about 20 times larger than a complete fruit fly brain and much more complex, the researchers said. However, the goal is to map the entire connectome of the mouse brain in the near future.

"I think at the moment the answer is no, it's not feasible, but I think everyone has very clear ideas about how these obstacles can be overcome. Hopefully in three or four years we can say: yes, it's possible," Collman told CNN.

However, he added that mapping the human brain's connectome with the same synaptic precision would be a much more difficult endeavor. "The human brain is about 1500 times larger than a mouse's, and that presents a number of obstacles... technical and ethical to accomplishing," he said.

However, it may be possible to trace axons throughout the human brain, even if not synaptic connections, added Dr. Clay Reid, a senior researcher in the field of brain science at the Allen Institute.

"The ability to reconstruct the entire human brain at the level of all connections... that's something for the very distant future," he added.

A new way to study Alzheimer's

The neocortex is particularly interesting to study because it is what distinguishes mammalian brains from those of other vertebrates, said Dr. Mariela Petkova, a researcher, and Dr. Gregor Schuhknecht, a postdoctoral fellow, both in the department of molecular and cell biology at Harvard University. Petkova and Schuhknecht were not involved in creating the mouse brain map.

"The researchers focused on this region because it is generally considered the center of higher cognition and plays a key role in sensory perception, language processing, planning, and decision-making," they wrote in a statement. published article along with the study.

"It is remarkable that these functions, although markedly different, are made possible by a building plan that is found, with some variations, in all cortical areas and in all mammals," they added.

Laboratory mice are already widely used to understand human diseases, and a better understanding of the form and function of the mouse brain will offer new opportunities to study human brain disorders such as Alzheimer's, Parkinson's, autism and schizophrenia, which are associated with disruptions in neural communication.

"If you have a broken radio and you have the wiring diagram, you'll be in a better position to fix it," da Costa said in a press release.

"We are describing a kind of Google map or building plan of this grain of sand. In the future, we can use this to compare brain connections in a healthy mouse with those in a disease model," he claimed. /Telegraph/