Narayanan Kasthuri

Narayanan Kasthuri, an Indian American assistant professor of neurobiology at the University of Chicago, is leading unprecedented research of brain cells. (uchicago.edu photo)

An Indian American assistant professor of neurobiology and researcher at the University of Chicago’s Argonne project is leading research into mapping billions of brain cells.

Scientists at the university and Argonne National Laboratory, including Prof. Narayanan Kasthuri, are combining new techniques in microscopy, neurobiology and computing to reveal the brain’s inner mechanisms in unprecedented detail, the university said in a report.

In the abstract, the brain is an electrochemical computer, operating on electrical impulses and chemical signals sent between cells. Though the individual pieces may be small, on the scale of mere nanometers, drawing the wiring diagram for this machinery is theoretically possible, and has been done for very simple organisms, it said.

But the size and complexity of the human brain create far bigger challenges. Scientists estimate that the brain contains nearly 100 billion neurons, the basic type of brain cell. Each of those neurons makes tens of thousands of contacts with other cells, bringing the number of connections into the quadrillions, or a million billion, it added.

A complete map of these connections would be nothing less than the largest dataset ever created. But within that massive inventory could lie answers to some of the most elusive scientific questions: the fundamental rules of cognition, explanations for many mental illnesses, even the biological factors that separate humans from other animals, the report went on.

“It’s a huge theory of neuroscience that all of our behaviors, all of our pathologies, all of our illnesses, all of the learning that we do, is all due to changes in the connections between brain cells,” said Kasthuri, assistant professor of neurobiology at the university and neuroscience researcher at Argonne, in the report.

Today, neuroanatomy involves the most powerful microscopes and computers on the planet. Viewing synapses, which are only nanometers in length, requires an electron microscope imaging a slice of brain thousands of times thinner than a sheet of paper, the university report noted.

To map an entire human brain would require 300,000 of these images, and even reconstructing a small three-dimensional brain region from these snapshots requires roughly the same supercomputing power it takes to run an astronomy simulation of the universe, it said.

Both of these resources exist at Argonne, where, in 2015, Kasthuri was the first neuroscientist ever hired by the U.S. Department of Energy laboratory.

Kasthuri brought with him automated methods he developed for efficiently mapping the brain. A diamond knife with an edge only five atoms thick cuts 50-nanometer-thin slices of human, mouse or even octopus brain, which float away on water to a conveyer belt that takes them sequentially beneath the gaze of an electron microscope, it said.

“At most other universities, I’d just have to give up this idea,” Kasthuri said in the report. “Even a small part of a brain I could never map, because even 1 percent of a mouse brain is something like 1,000 terabytes of data. No other university in the world, I think, could conceivably handle that.”

To reduce this complexity into more practical science, Kasthuri is starting small, the university noted.

Where other high-profile connectome projects have focused on building a complete map of the human brain, Kasthuri is focusing first on comparisons: between young brains and old, between animal brains and human, between “normal” brains and the brains of people with mental disorders, it said.

“I think the only way we’re going to understand the brain is by comparing it to other things,” he added in the report.

Beyond the age curve of learning, such a study could also address fundamental questions about how the adult brain is built, the report said.

The near-term benefits of brain mapping will be to equip scientists studying more elemental links between brain and behavior with a deeper understanding of the organ’s complex mechanical structure, the university report added.

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