catalyst

Research, Scholarship and Creative Achievement at UTSA

What it means to be Human

Neurosciences Institute delves into the mystery of the human brain


There are 100 billion neurons in your brain, each one reaching to touch a thousand others in a vast and complex network that would make the global power grid look like child’s play.

But the spongy, folded tissue inside your skull is much more than an electrical grid filled with cells. The brain, as UTSA’s Charles Wilson describes it, is the organ of the mind. It is the center of thought, perception and action— the things that make us human. It is also a complex biological system that presents one of the greatest remaining mysteries to science.

“The magnitude of the challenge is not for people who want to answer little questions. It is for people who want to take on big problems,” says Wilson, who holds the Roland K. and Jane W. Blumberg Professorship in Bioscience and is the director of UTSA’s recently established Neurosciences Institute.

Neuroscience has been a strong component of UTSA’s basic science program since the days of the university’s founding. But several years ago, Wilson spearheaded a mission to give UTSA a place at the table of research universities known for grappling with the mysteries of the brain. The Neurosciences Institute became official in 2008, folding into UTSA’s plan to become a top-tier research institution. In addition to offering its faculty members research and administrative support, the institute hosts brain outreach lectures for the public, welcomes acclaimed international neuroscientists to speak at UTSA, and provides collaborative opportunities for a team of 21 scientists who are working to understand the basics of how a healthy brain works and what goes wrong during neurological disease.

“It is a bigger problem than most of the problems we face in science, and it has to be addressed at many different levels, from molecular to human cognitive research,” Wilson says. “It is impossible to succeed if we focus too much. On the other hand, individual scientists have to focus their research. So the purpose of the Neurosciences Institute is to support the work of all these individuals and to collectively keep us on our mission to understand the brain and the mind at all those different levels.”

The institute brings together faculty members from diverse disciplines such as biology, mathematics and computer science. Individually, they study topics such as the basic biology and function of brain structures, cognitive issues including memory and language learning, and disease states such as addiction, Parkinson’s disease and Alzheimer’s disease. They share resources and ideas and collaborate on grant projects. Together, the scientists say, they are painting the picture of what it means to be human.

Synergy is a word that gets used a lot here. “In my mind, this is like a think tank,” says Brian Derrick, a professor of neurobiology who is devoted to studying memory and the hippocampal formation. “We work as a group, not just as collaborators. We are being forced to understand the work of everybody else, and we find that it helps us in the way we approach our own research.”

Still, there is a lot of diversity in individual research interests. Some faculty at the Neurosciences Institute are zeroing in on a single type of cell, while others are engrossed in understanding a broader process, such as the brain’s role in reproductive behavior or language learning.

There’s been a fundamental shift in the overall view of the brain, Derrick says. “We used to think functions were localized within different structures,” he says. “We are finding now that it is the kind of computation that the structure does [that] is what is important in whether or not the structure is involved in that function.

It is the mathematician’s perspective, and the way so many research efforts now begin— with mathematical modeling of the scientist’s hypothesis. Experiments follow to either confirm or disprove, or even refine the hypothesis.

Derrick begins with modeling as he tries to understand how short-term memories move to longer-term storage, a process that involves the hippocampal formation. The hippocampus is one of two regions in the brain that continue to make neurons throughout life, but beginning in middle age, this production of neurons slows.

“That seems to account for a lot of the memory impairments that one sees in older adults,” says Derrick. He is testing the theory that the newer neurons are responsible for new memories being formed, and as their production declines, people have a more difficult time with short-term memory.

“My research suggests that if you can stimulate the production and survival of these neurons, you improve memory,” he says.

Nicole Wicha, assistant professor of biology, focuses on a different cognitive process— how the brain understands language and how language can shape the brain. She is trying to define the neural basis for how the brain takes the simple sounds produced by a speaker and interprets them in complex, meaningful ways. One focus of her research is to understand how the bilingual brain manages to maintain its two languages separately, and at the same time easily switch between them when needed.

Language exposure affects other areas of cognition, she has found. People who learned multiplication tables in Spanish, for example, usually continue to compute basic math in Spanish throughout their lives, even if they become fluent in another language

“Our lab experience is showing that people tend to fall back on their language of learning for those concepts,” Wicha says. “The bilingual brain is really fascinating in that way.”

The lab is currently looking at how these concepts are remapped to a new language, for example, in bilingual education teachers who have to teach basic math concepts in their second language.

San Antonio’s diverse culture, mixed with native Spanish speakers from throughout Latin America, makes the city a living laboratory for her.

“It is a rich community to study language, especially in the bilingual brain,” Wicha says.

As a child, Kelly Suter was so fascinated with human reproduction that her parents dragged her off to a psychologist to find out why their 5-year-old was so interested in the diagrams in the family encyclopedia. There was nothing wrong, and the curious child grew up to become a college chemistry major, which led the budding scientist to the study of human endocrinology and chemicals called gonadotropin-releasing hormones. These are produced by specialized neurons in the brain, which pulsate hourly to release the hormones that regulate reproduction. Disruptions and abnormalities in this oscillating cycle are at the root of many fertility problems.

“While most people think reproduction is about things below the waist, really, reproduction is controlled by the brain,” says Suter, an assistant professor of biology.

Her work, supported by the National Institute of Child Health and Human Development, focuses on understanding how these specialized neurons release and control the hormone, and what goes awry during reproductive problems.

For some faculty, the challenge means peering inside the cell itself with high-tech tools capable of watching molecules in action.

Fidel Santamaria, assistant professor of biology, is using fluorescent dyes and two-photon microscopes that are sensitive enough to detect items one cubic micron in size

He is trying to track the minute changes within a cell that slowly lead to age-related mental decline.

“Why do people start losing memory and brain function?” he asks. “It begins in middle age. But if you look at the brain, you don’t see the changes; you don’t see massive cell death.”

Another research interest is the concentration of cholesterol that increases with age, particularly in people with Alzheimer’s disease. Santamaria wants to understand why this occurs.

Carlos Paladini, who came from Portland, Ore., four years ago, was drawn by the opportunity to collaborate with faculty already at UTSA who are at the leading edge of techniques in computer modeling, imaging and quantitative analysis.

Also an assistant professor of biology, Paladini is another who is focused on the internal workings of a cell within a critical brain circuit. His research concentrates on the dopamine neurons that are entwined with human feelings of satisfaction and pleasure. There are 300,000 of them clustered in the ventral midbrain—a small number compared to the overall billions of neurons in the brain. But dopamine cells are the ones that are hijacked by addiction and damaged by Parkinson’s disease.

Using mathematical modeling and advanced imaging techniques, Paladini is working to understand precisely what makes these neurons fire and how they are affected by different stimuli. Fluorescent dyes and advanced imaging techniques make it possible for him to examine the action of proteins on the surface of the dopamine neuron and see what sort of changes occur when the cells are exposed to substances such as addictive drugs. He also measures the voltage inside a single cell to record changes in electrical activity during these chemical exposures.

In a healthy brain, the reward-seeking response is vital to many positive and necessary things in life, such as the drive to succeed, the satisfaction of a meal, the pursuit of a mate, Paladini says.

“There are drugs on the market to treat addiction, but they turn off everything,” he says. “People lose interest in everything. We are trying to figure out how to turn off one part, the addictive response, and leave everything else alone.”

Wilson, when he is not wearing his administrative hat, has deep interest in the basal ganglia, an area where the brain generates its own autonomous activity that does not rely on external stimuli. He studies how sensory and motor signals interact in the basal ganglia and the role they have in the brain’s computations.

Essentially, Wilson says, the brain is a living computer, and diseases of the brain are errors in computations. Psychiatric diseases such as schizophrenia, degenerative diseases like Alzheimer’s, and genetic diseases such as Huntington’s, all have their onset when the brain makes mistakes.

“In all these diseases, ultimately what happens is electrical activity of the nervous system is pathologic,” Wilson says.

And with those 100 billion neurons in the brain, there’s no shortage for study. Plans call for adding five more faculty members to the institute in the next five years to expand the areas of specialized study. But every neuroscientist, regardless of where they focus, wants to find something that will offer hope to those who grapple with debilitating conditions, Wilson says.

“These diseases are horrendous, and they have been untouched by our medicine, for the most part,” Wilson says. “There are treatments, which have been great achievements. But still we don’t understand the basis of these diseases; we don’t have cures for them. This is the real challenge for neuroscientists.”

Wilson sees another quest as well—one that is first on his list of why he goes to work each day. It is the desire to understand what we are.

“That is probably the most fundamental question that humans ask,” he says. “What is it to be human?”

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