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A deep look at a human brain spot reveals peculiarities never seen before


A new vision of the human brain shows its cellular residents with all their wild and strange glory. The map, extracted from a small piece of a woman's brain, represents the varied shapes of 50,000 cells and 130 million connections between them.

This intricate map, called H01 for “human sample 1,” represents a milestone in scientists ’quest to provide increasingly detailed descriptions of a brain (SN: 2/7/14).

“It’s absolutely beautiful,” says neuroscientist Clay Reid at the Allen Institute for Brain Science in Seattle. "In the best way possible, it's the beginning of something very exciting."

Scientists from Harvard University, Google, and elsewhere prepared and analyzed the brain tissue sample. Smaller than a sesame seed, the little brain was about a millionth the volume of an entire brain. It came from the cortex – the outer layer of the brain responsible for complex thinking – of a 45-year-old woman undergoing surgery for epilepsy. After removal, the brain sample was rapidly preserved and stained with heavy metals that revealed cellular structures. The sample was cut into more than 5,000 thin wafer pieces and imagined with powerful electron microscopes.

Computer programs joined the resulting images, and artificial intelligence programs helped scientists analyze them. A short description of the resulting view was published as a prepress on May 30 at bioRxiv.org. The data set is available for free online.

These two neurons are mirror symmetrical. It is not clear why these cells take these forms. Lichtman Lab / Harvard University, Connectomics Team / Google

For now, researchers are just beginning to see what’s there. “We really just put our toe in this data set,” says study co-author Jeff Lichtman, a developmental neurobiologist at Harvard University. Lichtman compares the brain map to Google Earth: "There's jewelry to be found, but no one can say you've looked at it all."

But some “fantastically interesting” places have already appeared, Lichtman says. "When you have big data sets, you suddenly start highlighting these weird things, these weird things, these weird things."

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One such curiosity relates to synapses, connecting points where signals move between nerve cells. Typically, most axons that send messages touch a dendrite that receives messages only once. In the new dataset, approximately 90 percent of the connections were these contacts of a single success. Some cell pairs have a few more contacts. But every once in a while, researchers saw cells connecting several times, including a pair that were joined by a whopping 19 synapses.

Multiple connections were detected in the mouse brains, though not as abundant as in this human sample. And fly brains can also have many connections between cells, even if they are more scattered than new human connections, says neuroscientist Pat Rivlin of the Janelia research campus at Howard Hughes Medical Institute in Ashburn, Virginia. There, Rivlin works on the FlyEM project, which aims to create detailed maps of the fruit fly’s nervous system.

The large data set of the human brain provides a breakdown of how common these types of connections are, Reid says. And that raises the question of what can make these synapses extraordinarily strong in the brain.

black background with curled and connected purple puppiesIn their new database of human brain tissue, researchers found examples of unusual vertebrate (purple) nerve cell tendons, coiled like snakes.Lichtman Lab / Harvard University, Connectomics Team / Google

Lichtman speculates that these cells could force their target cell to act in a powerful way. Perhaps memorizing information, such as knowing 5 times 5 is 25 or knowing how to stop at a red light, depends on these powerful inputs that drive information efficiently through the brain.

Molecular neuroscientist Seth Grant of the University of Edinburgh points out that while the map is a valuable tool, it only shows the anatomy of the brain. Other research will help clarify the function and composition of molecules that drive brain behavior. For now, the map is “an exploratory tool,” he says.

A curiosity to explore further is the observation of the team of two nerve cells, or neurons, that seemed to be intertwined in a symmetrical dance. The images also revealed axons of neurons sending messages forming elaborate coils, unusual and mysterious whirlpools that look like coiled snakes. “We’ve never seen anything like it before,” Lichtman says. Once researchers were able to search for these coils, they appeared more and more.

These extremely detailed brain maps are the culmination of years of research, says Reid, who is working on mouse and human brain maps at the Allen Institute (SN: 8/7/19). “It’s this magical moment in history” when mapping tools such as computational methods, machine learning, and powerful microscopes are available, Reid says. "This job is just starting to see the light of day."

What these maps will eventually reveal is an assumption of either. Lichtman is wary about whether these maps will lead to a deep understanding of the brain. “I think the best we can do is describe it,” he says. "I hope at some point we get to a place where we are no longer surprised by what we see."



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