German terrorist Ulrike Meinhof hung herself in her prison cell in 1976, but her brain remained in captivity until late last year, when it was finally returned to her family for burial.

Scientists had kept the brain of this reporter-turned-urban guerilla for nearly 30 years, conducting studies that shed new light on Meinhof’s terrorist actions during the last decade of her life.

A bright journalist with left-wing sympathies, Meinhof underwent an operation in 1962 to remove a brain tumor; by the late 1960s she had left her husband and twin daughters and joined the Baader-Meinhof gang, which plagued West Germany in the early 1970s with robberies, bombings, and murders. A psychiatrist who studied Meinhof’s brain for five years says he found "pathological modifications" suggesting that the operation, in combination with other factors, may have caused her behavior to change from political sympathy to violent extremism. Other research showed that the tumor itself had caused changes in parts of the brain that controlled emotion.

That a person’s judgment and personality could be so drastically changed by disease—or the attempt to cure disease—raises fundamental questions about the meaning of cognition. In the human brain, the line between biology and the "essence of self" becomes blurred. How does what happened to Meinhof’s brain affect the person she was, as well as how we regard her? Where does brain end and mind begin?

An Expedition into Adaptability

Neurobiologist Michael Friedlander, Ph.D., says science is taking a stab at answering some of these complicated philosophical questions. "We’re now in the biological era of trying to understand some of the fundamental questions of life—questions that were first explored by philosophers and theologians. I don’t know how much science will be able to tell us, but it’s biology’s turn to add its input to these issues."

President George H. W. Bush declared the 1990s to be the decade of the brain, prompting a wealth of federal funding for research that has yielded much information over the past 10 years. But this oddly corrugated organ, which is central to every function of the human body, remains mostly a mystery. Now, to continue this expedition, neurobiologists and physicians at UAB have formed a collaborative research initiative called the Adaptive Brain Group, which will be housed in the Shelby Biomedical Research Building now under construction.

"We decided not to call ourselves a ‘brain institute’ or a ‘neuroscience center’ because we wanted to focus on processes and central principles that tie all kinds of brain and nervous-system research together," says Friedlander. "More than anything, the central aspect of the brain is its adaptability—its responsiveness to its environment."

Adaptation, says Friedlander, encompasses everything from the evolution of the species to the distrust we feel for people who betray us, from dislike for a food that once made us sick to addictive behaviors such as alcoholism.

"Even paralysis is a sign of the adaptive brain at work," he says. "We used to think that patients with spinal-cord injuries did not get better because the nerve cells simply did not have the capacity to regrow. But in studying other organisms—mostly aquatic critters such as frogs and fish—we’ve found that these cells do have the capacity to regrow. In fact, they try to regrow. But there’s something about the environment around the nerve cells in humans and other mammals that inhibits this growth. These cells run into chemical and physical barriers that prevent their regrowth, because the nervous system has ‘adapted’ to prevent the regrowth.

"Now, that might not sound like an adaptation—more like a disaster, particularly if you’re a paralyzed person. But if these cells were simply allowed to regrow and they did not connect properly, you could have a situation that’s even worse than paralysis—your brain might send a message to move your little finger but your whole arm might start waving around, for example. In our evolution, the strategy that has been best for us as organisms is to not have this regrowth capacity, since perhaps we don’t have the ability to rewire everything properly."

Imaginably, the better we understand how the brain performs these adaptations, the better we may be at controlling illnesses in the brain and repairing damages or maladies that occur. To that end, researchers in the new adaptive brain unit will collaborate to investigate every aspect of the brain, from memory to mood, at every stage of life.

The Big Work of Baby Brains

Lying in her crib, a newborn baby seems an otherworldly bundle of flailing limbs and mismatched facial expressions. Though she does not appear to be getting much accomplished, she is by far the most active person in the room. An infant’s brain is still assembling itself to regulate bodily activities both voluntary and involuntary, as well as to communicate, form relationships, learn emotions, and take some meaning from the world outside the womb. This tremendous activity continues for the first few years of life, and the health of the child depends on the success of millions of near-miracles that unfold in her brain.

Researchers who seek to understand this development often focus on the brain’s synapses, which are the communication points between nerve cells. In an embryo, neurons are formed at the central core of the brain and slowly migrate to their proper positions. For each of the hundred billion neurons that are in a human brain, there are thousands of synapses, meaning that there are about one quadrillion synapses in every brain—more than there are stars in the known universe.

"The synapse is the fundamental functional unit in the brain," says Lin Mei, Ph.D., who studies their formation. "If you don’t have synapses, you don’t have brain function." Synapses form in the brain before birth and for a few more weeks after birth, creating communication links within the brain and between the brain, the nervous system, and the muscles in the body.

Mei explains that, at first, these synapses actually overlap one another. Several motor neurons innervate the same muscle fiber, for example, but eventually the overlapping synapses disappear. "You can have only one contact for each," Mei says. "If you have a muscle fiber controlled by multiple neurons, the muscle does not know how to contract or when to contract—it gets confused." As connections are formed, the "extra" synapses are culled away.

Synapses and Seizures

Neurobiologist John Hablitz, Ph.D., says this busy time of early development makes the infant brain particularly fragile. "It’s a very seizure-prone period," he says. "With all these extra ‘feelers’ out, if something pushes the system—a high fever, for instance —some abnormal activity could occur." Seizures in children are surprisingly common, and although their impact is difficult to measure in such young patients, they can cause long-term problems.

Hablitz explains that a seizure occurs when the brain becomes overexcited. "There are different types of communication between synaptic cells," he explains. "Synapses can either excite one another and pass information, or they can inhibit communication. Both of these processes are necessary for normal brain function." If there’s a disruption in inhibition or an increase in excitability, the brain goes into seizures.

For people with seizure disorders that persist beyond childhood, the root of the imbalance can be painfully subtle, says Hablitz. "We think that sometimes the cortex of the brain doesn’t make the switch from the early developmental state to a more mature form. It’s thought that this is caused by abnormal physiology in the nerve terminals where synapses form, which keeps the brain in a persistent hyperexcitable state." So an adult epileptic brain in some ways still responds like a baby’s brain to stresses and stimuli.

Mei says disturbances in synaptic formations are at the heart of many problems that occur at birth or in childhood, from epilepsy to mental retardation. "Sometimes the neurons migrate to the wrong position, and sometimes the synapses have a hard time finding their targets. The highways are all mixed up and communication between neurons is mangled. The synaptic transmission itself could even be dysfunctional. We need to understand all of these processes better in order to understand what goes wrong."

"So many things occur simultaneously," says Hablitz. "When you think of all the things that can go wrong, it’s amazing that we actually do as well as we do."

But Hablitz notes that the brain also has remarkable abilities to compensate for problems that arise in these early stages of life. "For example, some people are born without a cerebellum, which is normally the part of the brain we use for walking and talking. But they can function fairly normally—if you saw them on the street, you wouldn’t know they’re missing a crucial part of their brains. While they aren’t going to be concert pianists, these people’s brains have adapted, and they manage very well."

The Meaning of Life:
to Learn and to Remember

From birth to death, nothing is more central to our brains than learning and memory. "We do it every day of our lives," says Friedlander. "We take our experiences and put them together in our brains in a meaningful way." From the calculus we study in school to the smell of the cologne or perfume worn by our first love, learning and memory-making is what makes up our lives. But how our thoughts and memories relate to cellular processes in the brain is not at all clear. "This is a fundamental property of human beings that is very poorly understood at the scientific level," Friedlander says.

"But we do know that one of the major sites of change in our brains when we learn and remember is in our synapses," he continues. "We think these may be the most important players to understand in terms of learning and memory."

One of the fundamental findings of the last decade is the plasticity of synapses—their ability to alter their strength in response to experience and the context of a situation. "As this happens, the synapses are actually changing shape—getting fat, getting short, becoming concave or convex, forming mushroom shapes," says Friedlander. "We knew this happened in the developing brain, but we didn’t know that as adult brains think and learn it happens dynamically too." The question now is how these cellular changes become knowledge and memory.

A seahorse-shaped part of the brain, the hippocampus, is the focus of much research into learning and memory. It is there that basic, functional learning is consolidated into memories.

The hippocampus is tied particularly to spatial learning. Imagine you check into a motel room and you go to sleep. Late that night you get up to go to the bathroom. In your own home this trek could be made with no hint of light, but make the journey in a pitch-black motel room and your toe is likely to make painful contact with the television credenza. This is because the neurons in your brain’s hippocampus have not yet formed a spatial map of the room around you. Lucas Pozzo-Miller, Ph.D., is studying the cellular process of spatial learning in rats, via a family of proteins called neurotrophins, which are necessary for synapses in the hippocampus to remain plastic.