Using a piece of cerebral matter of mouse the size of a grain of sand, scientists created the first precise three -dimensional map of the brain of a mammal .
The map details form, function and activity of 84,000 neurons branched structures that shoot messages through a long arm called axon, and then over 500 million synapses, plus 200,000 brain cells. The tiny piece of fabric contained 5.4 kilometers of neuronal wiring – almost once and a half the length of New York Central Park.
The work is the result of almost a decade of research by 150 scientists in 22 institutions led by the Allen Institute for Brain Science, the Baylor Medical School and the University of Princeton.
“A byproduct of this whole project shows us how incredibly beautiful the brain is,” said Dr. Forrest Collman, the Allen Institute’s associated data and technology director, in a video shared by the organization.
“Just looking at these neurons shows your details and climbs in a way that makes you enjoy the brain with a feeling of admiration, like when you look at a very, far away galaxy,” he added.
The amazing map represents only 1/500 of a mouse’s total brain volume, but the team ended up with 1.6 petabytes of data – an impressive amount equivalent to 22 years of uninterrupted HD video, which the project, known as the Cortical Machine Intelligence Program (Microns), has already made publicly available.
Researchers described the work in several published articles in the journal Nature on April 9.
Developing brain activity
To make the map, scientists at the Baylor School of Medicine in Houston started using specialized microscopes to record brain activity in a portion of cubic 1 millimeter tissue in the visual cortex of a laboratory mouse – where the animal processes what it sees – over a few days.
The researchers assured that the mouse was awake and visually stimulated during the capture of images, making the animal run in a treadmill and watch scenes of 10 seconds of various films, including “Matrix” and “Mad Max: Road of Fury.” Youtube clips of extreme sports such as motocross, Luge and Jumping base were also part of the viewing rotation, according to a statement from Princeton University.
Then, after euthanizing the mouse, researchers at the Allen Institute in Seattle took the same cubic millimeter of brain and sliced it in more than 28,000 layers, each with 1/400 of the width of a human hair, and photographed each slice over the process. Then they rebuilt the images in a compound.
“This took us about 12 days and 12 nights with the team turning on shifts; not because we were cutting by hand, it is an automated machine,” said Dr. Nuno Maçarico da Costa, an associate investigator of the Allen Institute. “We needed to be there to stop at any time if we thought we were going to lose more than one section in sequence.” If that happened, Costa said the experiment would have to start from scratch, adding that the whole process was very “stressful”.
A team from Princeton University in New Jersey later implemented machine learning and artificial intelligence tools to trace the outline of each neuron through the slices, coloring the neurons to illuminate them individually in a process called segmentation. The information generated by AI is validated or revised by the scientists involved, a process that is still in progress.
The work has culminated in a unified view of what scientists are calling a “connectom” of the mouse’s brain, which shows how specific parts of the mouse’s brain are organized and offers insights on how different cell types work together.
“Connectoma is the beginning of the digital transformation of brain science,” said Dr. Sebastian Seng, Professor Evnin of Neuroscience at Princeton University and Professor of Computer Science.
“With some keyboard touches, you can search information and get the results in seconds. Some of this information would have taken a whole doctoral dissertation to get before” “and that’s the power of digital transformation,” he said in a press release.
Impossible challenge?
Maping the brain in this way for a long time was considered an impossible challenge. Molecular biologist Francis Crick, who won the Nobel Prize for describing the DNA structure, suggested that neuroscientists would never be able to achieve such a detailed understanding of the brain.
“It’s no use asking the impossible, such as the exact diagram of connections to a cubic millimeter of brain tissue and the way all your neurons are firing,” he wrote at Scientific American in 1979.
The “connectoma” of the mouse brain is based on similar work with even smaller creatures: the nematode Conductoma Clegans was completed in 2019, and scientists revealed a map of all brain neurons in 2024.
A cubic millymeter of mouse brain is about 20 times larger than the full brain of the fly, and much more complex, the researchers said. Even so, the goal is to be able to map the entire brain connectom of mice in the near future.
“I think now the answer is no, not viable, but I believe everyone has very clear ideas about how they could break these barriers. We hope that in three or four years, we can say yes, it is possible,” Collman told CNN.
However, he stated that mapping the human brain connectoma in similar synaptic resolution would be a dramatically more difficult enterprise. “The human brain is about 1,500 times larger than a mouse’s brain, and this brings a series of technical and ethical barriers to do it,” he said.
However, it may be possible to track axons throughout the human brain if not synaptic connections, added Dr. Clay Reid, a senior researcher in brain science at the Allen Institute. “The prospect of rebuilding the whole human brain at the level of all connections, this is something for a distant future.”
A new way to study Alzheimer’s
Neocortex is particularly interesting to study, because this region of the brain is what distinguishes the brains from mammals from those from other vertebrates, Dr. Mariela Petkova, an associated researcher, and Dr. Gregor Schuhknecht, postdoctoral student, both from the Harvard University Department of Molecular Biology. Petkova and Schuhknecht were not involved in creating the mouse brain map.
“The researchers focused on this region because it is generally considered the seat of higher cognition and plays a key role in sensory perception, language processing, planning, and decision making,” they wrote in an article published along with the research.
“Notably, these apparently different functions are made possible by a model that can be found, with some modifications, in all cortical areas and in all mammals.”
Laboratory mice are already widely used to understand human diseases, and a better understanding of the mice’s brain shape and function will present new possibilities for studying human brain disorders such as Alzheimer’s, Parkinson, autism and schizophrenia involving disorders in neural communication.
“If you have a broken radio and have the circuit diagram, you will be in a better position to fix it,” said Da Costa in a press release. “We are describing a kind of google maps or floor plan of this grain of sand. In the future, we can use this to compare the brain circuit into a healthy mouse with the brain circuit in a disease model.”
This content was originally published in scientists reveal advance in brain research considered impossible on the CNN Brazil website.
Source: CNN Brasil
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