Researchers have unveiled a small portion of the human brain with astonishing detail, resulting in a cell map recently published in "Science" and available online. The map reveals brain cells known as neurons, cells forming structures around themselves, and new connection patterns between nearly mirror-image pairs of neurons.
Based on electron microscopy data rendering, the image displays the positions of neurons in a segment of the brain cortex. Image source: Harvard University
The 3D atlas covers approximately 1 cubic millimeter of volume, equivalent to one millionth of the entire brain, containing about 57,000 cells and 150 million synapses, the connections between neurons. It comprises a massive 1.4 petabytes of data. Viren Jain, a neuroscientist at Google in the United States and one of the paper's authors, asks, "How will we ever truly grasp all this complexity?"
The brain segment was taken from a 45-year-old woman undergoing surgery for epilepsy treatment. This segment is from the brain cortex, responsible for learning, problem-solving, and processing sensory signals in the brain. Researchers soaked the sample in a fixative and stained it with heavy metals to make cells more visible.
Neuroscientist Jeff Lichtman and colleagues at Harvard University in the United States sliced the sample into about 5,000 sections, each only 34 nanometers thick, for imaging with an electron microscope.
Subsequently, Jain's team developed an artificial intelligence model to stitch together the microscope images and reconstruct the entire sample in 3D. "I remember that moment, opening the atlas, observing an individual synapse in the female brain, then zooming out to millions of other pixels."
Upon detailed examination of the model, researchers discovered unconventional neurons, some of which had as many as 50 connections to each other. Jain remarked, "Typically, two neurons have at most a few connections between them." Elsewhere, the model showed neurons with tendrils, tendrils coiling around themselves to form structures. Jain added, "No one has seen anything like this before."
The research team also found pairs of neurons that were almost perfect mirror images of each other. "We found two sets of dendrites moving in two different directions, sometimes exhibiting a kind of mirror symmetry," Jain said. The function of this in the brain is currently unclear.
The atlas is so vast that most of it still requires manual inspection, and errors may still exist in the process of stitching together so many images. "Hundreds of cells have been 'proofread,' but obviously, this is only a fraction of over 50,000 cells," Jain noted.
Researchers hope others can help proofread sections of the atlas that interest them. They also plan to extract similar brain samples from other individuals, but drawing a complete map of the entire brain is unlikely in the coming decades.
Hongkui Zeng, director of the Allen Institute for Brain Science in the United States, stated, "This paper is truly a masterpiece of the human brain cortex dataset. The freely available extensive data will allow researchers in the field to delve deeper into the microcircuits of the human brain cortex."
A deeper understanding of how the brain cortex functions may provide clues on how to treat some mental and neurodegenerative diseases. Yongsoo Kim, a neuroscientist at Pennsylvania State University in the United States, said, "This atlas offers unprecedented detail, revealing new rules of neural connections and aiding in deciphering the inner workings of the human brain."
For more information on the paper, visit: https://doi.org/10.1126/science.eadk4858
