Wang connects brain's form to function

Molecular biology professor Sam Wang's 15 minutes in the spotlight came in the months leading up to the presidential election. His launch of a website that analyzed election surveys garnered national attention as one of the best predictors of what the election might hold.

But in the end, his analysis predicted John Kerry would win.

He might not have accurately predicted what Americans were thinking, but in his primary area of research he seeks to understand how the brain works.

In doing so, he is hoping to answer some of the most fundamental questions about life, learning, memory and intelligence.

And in time, Wang's life's work may leave a more lasting legacy than his abortive attempt at being a pundit.

"My feeling was that I had this idealistic view that I wanted to work on the most fundamental problems I could get my hands on," said Wang, a rising star in neuroscience research.

When approaching his work, Wang was not shy of some of the tougher philosophical and existential questions surrounding the research.

"Where did we all come from? What are we all made of? And how are we able to ask the first two questions? In terms of modern science these are core questions. These are the ones that got me excited," he said.

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Wang and his lab group of eight students spend their days studying the brains of mammals in Guyot Hall. They study their design and how that affects intelligence.

"We're interested in how brains learn and change in response to experiences in the world," he said.

In trying to understand intelligence, Wang is grappling with how animals form and store memories.

His idea is based on nerve cell connections in junctions called synapses, which have a strength that can change over time.

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A brain can receive thousands of inputs in these synapses at once, which form a complex network within the brain.

"If you can take tools of network analysis and how networks learn and store information, [you can] use those ideas to try to understand brain architecture," Wang said.

Wang is attempting to use theoretical approaches to understand brain architecture and inner workings.

Recently, he has made some important discoveries in which he compared the human brain structure to the avian brain.

Humans brains are 80 percent cortex, the largest percentage among all organisms, Wang said.

"In mammals, the thing that seems to be a hallmark of behavioral complexity and social complexity is having a big cortex. What we found is that birds don't have a cortex, but they have a similar structure in their forebrain," he said.

Birds with larger forebrains tend to exhibit more social complexity, Wang added.

In arriving at his conclusions, Wang studied brains of many birds including crows, parrots, ducks and quail, which led him to realize there is as much variation among birds' brain structures as there is in mammals'.

For example, crows, which exhibit the most socially complex behavior among the birds studied, also have the largest forebrains.

"We discovered something deep about what it is that makes the brain intelligent in a bird that in some sense is shared in structure with mammals. So one thing that would be really interesting would be to start thinking about how you would extend that to even other animals," Wang said.

Attempting to compare intelligence across species raises the question of how humans have defined intelligence.

"One way to define it . . . is we are the only [intelligent species], so if you define intelligence as making technology, then we're it. There are no dolphins that make radios; there are no octopuses that fly planes," he said, laughing.

Wang is attempting to broaden the definition of intelligence to take into account what brain architecture produces behavioral complexity, and to define this idea in other animals.

"Anthropologists and ecologists will typically define intelligence as things like toolmaking, social intelligence, social complexity, and so I'm very interested in the physical basis of that," he said.

A world of synapses

Wang's lab is also currently researching how a single synapse works.

Using a laser-based tool in a process called two photon microscopy, the lab examines how a single synapse and nerve cell, which receive thousands of inputs at once, organize and assimilate this information.

"There are these complex patterns that our brains get that are turned into useful knowledge," Wang said. "We have the hope of learning enough about these rules at the single synapses and then being able to apply it to the behavior of the animal."

His research has led him to focus on the hippocampus — which is responsible for factual and spatial learning — and the cerebellum, which deals with motor learning and integrating sensory information.

"We're trying to develop technology that can emulate the kind of events that may happen in a living brain, and look at them under conditions where we can observe the events directly," he said.

Wang's technology is revolutionary because it does not use probes, electrodes or only one location in a nerve cell for the experiments.

To recreate what inputs would look like in a real brain, Wang steers a laser beam to different points in the tissue, and can therefore activate brain tissue at thousands of cell locations each second. He described the process as similar to playing a piano.

Changes can be seen in the tissue because of fluorescent proteins injected into the cells. The proteins fluoresce based on the activity of the synapses.

"You can essentially see chemical changes within the cell," Wang said.

A breakthrough came when Wang and his research team realized that the signal between synapses is a binary event. The distinction, Wang said, is that the synapse behaves like an on-off switch, rather than a knob on a stereo with multiple settings.

"That totally changes how one thinks about memory storage in the brain. Instead of memory storage being some analog quantity, now we think that memory storage is digital," he said.

Wang's research, though still speculative and unpublished, represents a new approach to thinking about brains theoretically.

And now Wang's research has brought renewed interest in the theory of digital memory storage.

Many scientists thought that digital memory storage was unrealistic, Wang said. "What we're showing is that maybe that's not so unrealistic."

Wang said he dreams that his research will one day become part of the science curriculum.

"Every sentence in a science textbook is based on some study that somebody did someplace . . . I would love to do things that get into textbooks within five years. I would love to look in a textbook and be like, 'Yeah, I did that,'" Wang said.

"It sounds a little bit corny but on some level that's a measure of whether you really discovered something," he added.