Biological puzzles abound in an up-close look at a human brain

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.

This digital drawing of a person's head shows the brain inside. An arrow points to the bottom left side of the brain.
During surgery for epilepsy, a surgeon removed a bit of a woman’s brain, a piece that became the starting material for this brain map.Google

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?”

  1. Blue, yellow, orange and red nerve cells with long tendrils are packed together in this digital reconstruction of brain tissue.
  2. A triangular-shaped nerve cell is surrounded by blue thin axons on of its branches.
  3. A green strand with little bulges along it is touched by a thinner blue strand, showing where two nerve cells touch.
  4. A nerve cell colored yellow on the top is the mirror image of a nerve cell colored pink on the bottom. Both cells have complex branching shapes.

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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