By the time President Barack Obama made the human brain a national research priority with $100 million in BRAIN Initiative funding, Spirou was leading only one of about ten labs in the world that were using large-scale 3-D reconstructions of neurons to more fully understand what’s going on in the center of the self.
On a cold winter day in the WVU Center for Neuroscience, Michael Morehead, a computer science graduate student, used a tablet he programmed to rotate a 3-D picture on a group of flat-panel televisions. The image in front of the group of scientists depicted eight neurons from a fetal mouse in the second month of gestation. Long tentacled arms reached out to meet other brain cells. Connections formed. The unborn mouse’s brain was virtually sparking to life before their eyes.
With the touch of a finger to pad, Morehead can remove a cell from the screen or take the viewer to a different time in the cell’s development.
George Spirou sits in front of the 3-D brain map in his neuroscience lab.
To the uninitiated, it can be cool to put on the 3-D glasses and see the long fibrous-looking dendrites reach off the screen toward your eye. But what is even more fascinating is getting the rare chance to see a brain cell—like one of the many in your own head—growing, competing with other brain cells to build a lasting connection, and setting a living being on its way toward behavior and thought.
“It’s incredibly difficult for humans at our macroscale to perceive this very minute world with a reasonable understanding,” Morehead said. What can really help is if you can blow it up to our size.
“It’s incredibly difficult for humans at our macroscale to perceive this very minute world with a reasonable understanding.” —Michael Morehead
“It’s almost like the invention of gunpowder in warfare,” he said of this approach. “It’s such a paradigm shift. When this is done—when the BRAINInitiative’s over—if we can model an entire brain pretty accurately, the avenues that are going to open up are just unfathomable. You can’t even imagine what’s going to happen in the next 20 years.”
Paul Holcomb, a neuroscience graduate student, was chief author on the lab’s most recent paper on an auditory area of the brain that has many large synaptic contacts called the Calyces of Held—named for the calyx that surrounds the base of a flower and for Hans Held, who first saw them in the late 1800s. Holcomb said this modeling allowed the team to see a more accurate picture of connections between brain cells.
These 3-D models provided a more accurate view of the cells in the brain than previous studies relying on 2-D or rough 3-D models. This powerful technology has allowed the Spirou lab to challenge some long-held beliefs about the area of the brain they work in, Holcomb said.
All of these smaller steps in correctly understanding areas of the brain and their function will be critical in treating neurological diseases such as Alzheimer’s, Parkinson’s, and schizophrenia.
Students examine brain cells at a microscopic level in Spirou’s lab at the WVUHealth Sciences Center.
“If we understand how the normal brain is wired, then we can begin to understand how things go wrong when it is miswired,” Holcomb said. “And if that’s the case, then we can potentially intervene and create devices similar to things like deep brain stimulation that is being used to treat Parkinson’s.”
Spirou compares current knowledge of the brain to the Asian tale of three blind men drawing conclusions about what an elephant is like by examining one part and believing the whole is all tusk, limb, or tail.
The long-standing problem has been a too-small sample size. Now, one set of these image data can be two terabytes or larger.
“When you sit back in your chair and you think about it,” Spirou said, “every neuroscientist is throughout their career alternately depressed and energized by the sheer magnitude of the challenge.”
“I think that there’s more optimism now than ever before in large part because technologies are there to collect and analyze larger data sets.”
INTERCONNECTING
When Spirou, a WVU School of Medicine researcher, was first mapping cells, it took him two years to map 50 neurons. Now, with a set of image files fed into a computer, the lab can access pictures of 300 neurons within hours.
And with this leap in knowledge, Spirou intends for WVU to also leap forward. While brain mapping, referred to as connectomics, is burgeoning, he wants the University to use its network of skilled and passionate researchers to keep us on the cutting edge.
He wants to grow the 50 labs across the campus that study neuroscience in the fields of chemistry, biology, physics, psychology, behavioral pharmacology, and clinical fields of neurosurgery, psychiatry, and neurology to encompass engineering, computer science, and mathematics, among others. The Center for Neuroscience intends to raise a $10 million endowment to grow the number of labs at WVU contributing to neuroscience research to 75 and be consistently nationally competitive in attracting the very best faculty.
“What better time and place to do it than when the entire field is in a transformation?” he said. “And with key investments in the right people, we can transform ourselves at the same time.”
He knows this is sound strategy because it’s how the field has successfully developed at WVU. New hires in the stroke group and neurosurgery are examples of those propelling neuroscience research forward in coordination with other labs across the Center.
And then there are the students who wanted in on the dream.
SCIENCE (NO LONGER FICTION)
Morehead, a Bridgeport, West Virginia, native, was the teaching assistant in a computer science class when Spirou came to recruit students to participate in running the 3-D system. He’s a technophile who’s aware of much of the latest public innovations. And he’d never heard of anyone manipulating perfectly accurate 3-D renderings of the brain.
“That to me was science fiction at the time,” Morehead said. “I didn’t think anyone in the world was doing that.”
“I think that there’s more optimism now than ever before in large part because technologies are there to collect and analyze larger data sets.” —George Spirou
Now he’s doing that, and the techie inside him hopes to see how computer-assisted mapping of the brain can lead to learning more about the brain, which could then lead to more ways to advance technology and expand even more what we know about ourselves.
Holcomb has become an advocate of connectomics and public education on the brain.
At a recent WVU David C. Hardesty Jr. Festival of Ideas talk, Holcomb stood in front of an audience and gave them a basis for thinking about the brain — what we know, what we don’t, and what we can accomplish in the next few decades. He said scientists should be providing the public with a “user’s manual” for the brain.
“According to Scientific American, we’re currently in the century of the brain, and I think that’s really telling in terms of where the research is going,” he said.
“We’re going to learn a lot about the brain in the next even ten years. And I want to be at the forefront of that. I want to be pushing the envelope in terms of using technology to understand how the brain’s circuitry is formed. And the Spirou group is doing one part of a huge project in trying to make that happen.”