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Pittsburgh Supercomputers Crunch Data To Create First Detailed Vertebrate Brain Map

A zebrafish larva used in research at the University of Exeter.

For the first time, scientists have created a three-dimensional map of a vertebrate brain on a nanometer scale.

A nanometer is one-billionth of a meter, and at this level, one can see individual neurons and how they connect to each other.

Dr. David Hildebrand said the project represents a step forward in brain imaging, particularly at a small scale.

“We are now able to leverage modern technologies, both imaging technology and computer technology, to image at nano-meter scale resolutions,” Hildebrand said. “Small brains, but entire vertebrate brains.”

He said the same technique could eventually be used for larger animals, or to study sections of human brains affected by disease.

When he was a Ph.D. student at Harvard University, Hildebrand sliced a tiny zebrafish larva brain into 18,000 sections and took pictures of them with an electron microscope. The brain is about 1 mm wide – less than the thickness of a penny – so each slice is just a few hundred atoms thick.

Hildebrand gave the tiny zebrafish larva pictures to Art Wetzel at the supercomputing center, who was tasked with assembling the pieces back into a digital whole. He said it was kind of like putting a thinly-sliced loaf of bread back together.

“The slices get smashed down and distorted as you cut them," Wetzel said. "So in order to study the details of the fish, these distortions have to be corrected and the whole fish data reassembled into its proper 3-D organization."

Wetzel used software he developed for just such endeavors, but said the zebrafish brain was far more complex than any similar project he’d done before.

“The previous reconstructions that were complete organisms are a little roundworm known as c elegans, that only has 300 neurons, whereas the fish here has more than 100,000 neurons in their brain, so it’s a much more challenging task,” Wetzel said.

The zebrafish is used commonly in research into vertebrate development, physiology and disease, because it breeds quickly and is transparent in the larval stage, making its anatomy easier to study.