It’s a bit like seeing a world in a grain of sand.
Except the view, in this case, is the exquisite detail inside a bit of human brain about half the size of a grain of rice. Held in that minuscule object is a complex collective of cells, blood vessels, intricate patterns and biological puzzles.
Scientists had hints of these mysteries in earlier peeks at this bit of brain (SN: 6/29/21). But now, those details have been brought into new focus by mapping the full landscape of some 57,000 cells, 150 million synapses and their accompanying 23 centimeters of blood vessels, researchers report in the May 10 Science. The full results, the scientists hope, may lead to greater insights into how the human brain works.
“We’re going in and looking at every individual connection attached to every cell — a very high level of detail,” says Viren Jain, a computational neuroscientist at Google Research in Mountain View, Calif. The big-picture goal of brain mapping efforts, he says, is “to understand how human brains work and what goes wrong in various kinds of brain diseases.”
The newly mapped brain sample was removed during a woman’s surgery for epilepsy, so that doctors could reach a deeper part of the brain. The bit, donated with the woman’s consent, was from the temporal lobe of the cortex, the outer part of the brain involved in complex mental feats like thinking, remembering and perceiving.
After being fixed in a preservative, the brain bit was sliced into almost impossibly thin wisps, and then each slice was imaged with a high-powered microscope. Once these views were collected, researchers used computers to digitally reconstruct the three-dimensional objects embedded in the piece of brain.
Some of those objects were surprising. Certain nerve cell pairs had extremely tight bonds, making 50 or more contact points with each other. “This is like if two houses in the neighborhood for some reason had 50 different phones connecting just those two houses,” Jain says. “It’s like, what’s going on here?”
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These nerve cells are all excitatory, which means they send signals to other cells that spur them into action. Their colors indicate different sizes of the main cell bodies. Google Research and Lichtman Lab/Harvard University; Rendering by D. Berger/Harvard University -
This nerve cell (white) is intensely connected with other cells. Shown here are contacts from 5,600 message-sending axons (blue). Google Research and Lichtman Lab/Harvard University; Rendering by D. Berger/Harvard University -
This message-sending axon (blue) contacts a target cell’s dendrite (green) many times, creating what might be an unusually strong connection between two nerve cells. Google Research and Lichtman Lab/Harvard University; Rendering by D. Berger/Harvard University -
The new brain map turned up pairs of nerve cells with eerily similar mirror-image shapes. It’s unknown how these cells create this symmetry, or why it happens. Google Research and Lichtman Lab/Harvard University; Rendering by D. Berger/Harvard University
Other views revealed mysterious whorls formed by message-sending tendrils called axons. “The axon would loop in on itself and make a giant knot,” Jain says. “We definitely didn’t expect to see these.” Scientists don’t know why these swirls exist.
And some nerve cells in the deepest layer of the brain bit appear to have mirror-image twins — another mystery.
These results don’t necessarily change the view of how the brain works. “It’s more like, ‘Oh, we’ve found this new structure in nature. Maybe there’s something really important about it. We’ll have to study it further,’” Jain says. Next up, he says, is scaling up to create a similar map for a piece of mouse brain that’s 10 to 15 times bigger than the piece used in the new study. Researchers also hope to map more human brain samples.
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