Researchers have mapped a tiny piece of the human brain in astonishing detail. The resulting cell atlas, which was described today in Science1 and is available online, reveals new patterns of connections between brain cells called neurons, as well as cells that wrap around themselves to form knots, and pairs of neurons that are almost mirror images of each other.
The 3D map covers a volume of about one cubic millimetre, one-millionth of a whole brain, and contains roughly 57,000 cells and 150 million synapses — the connections between neurons. It incorporates a colossal 1.4 petabytes of data. “It’s a little bit humbling,” says Viren Jain, a neuroscientist at Google in Mountain View, California, and a co-author of the paper. “How are we ever going to really come to terms with all this complexity?”
Slivers of brain
The brain fragment was taken from a 45-year-old woman when she underwent surgery to treat her epilepsy. It came from the cortex, a part of the brain involved in learning, problem-solving and processing sensory signals. The sample was immersed in preservatives and stained with heavy metals to make the cells easier to see. Neuroscientist Jeff Lichtman at Harvard University in Cambridge, Massachusetts, and his colleagues then cut the sample into around 5,000 slices — each just 34 nanometres thick — that could be imaged using electron microscopes.
Jain’s team then built artificial-intelligence models that were able to stitch the microscope images together to reconstruct the whole sample in 3D. “I remember this moment, going into the map and looking at one individual synapse from this woman’s brain, and then zooming out into these other millions of pixels,” says Jain. “It felt sort of spiritual.”
A single neuron (white) shown with 5,600 of the axons (blue) that connect to it. The synapses that make these connections are shown in green.Credit: Google Research & Lichtman Lab (Harvard University). Renderings by D. Berger (Harvard University)
When examining the model in detail, the researchers discovered unconventional neurons, including some that made up to 50 connections with each other. “In general, you would find a couple of connections at most between two neurons,” says Jain. Elsewhere, the model showed neurons with tendrils that formed knots around themselves. “Nobody had seen anything like this before,” Jain adds.
The team also found pairs of neurons that were near-perfect mirror images of each other. “We found two groups that would send their dendrites in two different directions, and sometimes there was a kind of mirror symmetry,” Jain says. It is unclear what role these features have in the brain.
Proofreaders needed
The map is so large that most of it has yet to be manually checked, and it could still contain errors created by the process of stitching so many images together. “Hundreds of cells have been ‘proofread’, but that’s obviously a few per cent of the 50,000 cells in there,” says Jain. He hopes that others will help to proofread parts of the map they are interested in. The team plans to produce similar maps of brain samples from other people — but a map of the entire brain is unlikely in the next few decades, he says.
“This paper is really the tour de force creation of a human cortex data set,” says Hongkui Zeng, director of the Allen Institute for Brain Science in Seattle. The vast amount of data that has been made freely accessible will “allow the community to look deeper into the micro-circuitry in the human cortex”, she adds.
Gaining a deeper understanding of how the cortex works could offer clues about how to treat some psychiatric and neurodegenerative diseases. “This map provides unprecedented details that can unveil new rules of neural connections and help to decipher the inner working of the human brain,” says Yongsoo Kim, a neuroscientist at Pennsylvania State University in Hershey.