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The plasticity of the human brain allows it to learn and adapt to all sorts of new circumstances.

Changing your mind

Experts gathered at the University last week to tackle questions about how the brain adapts

By Deane Morrison

Sept. 22, 2006

Understanding how the human brain works by studying one neuron at a time is like trying to understand a play by listening to only one character.

It's a difficult task because it's the interaction between a play's characters that makes it come to life -- just as it's the interaction between neurons in the brain that triggers learning and understanding.

Learning to understand those interactions is the monumental task undertaken by neuroscientist and Regents Professor Apostolos P. Georgopoulos, who was among the speakers at the presidential symposium on The Adaptive Brain held on the Twin Cities campus Sept. 14 and 15. The symposium brought together world-renowned brain researchers from Harvard, Stanford, Cambridge and other universities to share their insights into how the brain adapts to a changing environment, whether it be caused by normal development in utero, ingestion of addictive drugs, injury or the learning that all of us do every day. The researchers spoke of brain plasticity, meaning its ability to form new connections and patterns of activity, and adaptation, or adjustment to new conditions, which plasticity makes possible. In addition to the work of Georgopoulos, the symposium featured work by fellow University researchers Karen Hsiao Ashe and Paul Letourneau. But first, a bit of background on the basic units of the brain: neurons. The job of neurons is to talk to each other, which they do by firing off signals that may either excite or inhibit activity in other neurons. When a neuron fires, a pulse of electrical activity passes down its axon, a long extension reaching out to another cell. The membrane at the far tip of the axon releases molecules of a messenger, called a neurotransmitter, into an extremely narrow space between the axon and a target neuron. The neurotransmitter diffuses across the gap and is picked up by the target neuron, which may generate its own electrical pulse in response. These junctions between neurons are called synapses. Without the gaps, or synaptic clefts, between neurons, it would be very difficult to keep the electricity in one neuron from automatically jumping to other neurons, resulting in a disorganized jumble of signals.

"All learning focuses on synaptic interactions," says Georgopoulos. "Learning is a modification of synapses, and that is the result of crosstalk."

Much brain research has centered on the activity of single neurons, such as noting how different cells in the retina respond to all kinds of optical signals. This work has laid a solid basis for neuroscience, but in order to understand behavior, much must be learned about the complex ways cells work in concert. Neuron communication isn't one-way or even two-way; it is full of multidirectional "crosstalk," just like the communications within any large group of people. This is where Georgopoulos comes in. "All learning focuses on synaptic interactions," says Georgopoulos. "Learning is a modification of synapses, and that is the result of crosstalk." Consider learning to play a scale on the piano. Neurons must perceive the locations of keys and instruct hand and arm muscles what to do. Neurons receive input from many other neurons and are capable of talking back and forth in groups called neural circuits or neural networks. As one practices scales, transmission of signals across certain synapses becomes easier, perhaps because more neurotransmitter is released or inhibitory signals from other neurons are weakened. Feedback from the sound of the piano induces new rounds of activity. As neurons talk to each other, they "figure out" which connections to strengthen and which to weaken, eventually forming a superhighway of signals in response to a conscious command to play a scale. At this point, playing a scale becomes a fluid, effortless movement rather than eight laborious and ear-punishing steps. This kind of give and take is at the heart of brain function, yet, says Georgopoulos, "No one has focused on interactions and behavior, ever." In his research, he uses several different technologies to record the activity of multiple neurons at once. He has also developed the first procedures to evaluate both plasticity and adaptation at the whole brain level, using such techniques as recording activity of neurons and imaging the brain to see where and when it is active. Georgopoulos focuses on relations between spatial signals in the brain, such as happen when one is mentally tracing a movement or distinguishing up from down. "For example, as one solves a maze-that is, finds the exit-interactions around neurons change in an orderly fashion depending on the direction of movement in your mind," he says. "Single neuron activities may not change, but interactions do." Think of a play where one character keeps saying "Yes." That single response could drive all kinds of changes in plot and outcome, none of which would be obvious from recording only the "yes-man" neuron. Georgopoulos is also leading research on how neurons' own behavior may affect their responses to signals from other neurons. That is, neurons may fire in patterns according to how they have previously fired. Consider a person listening to another person talk. The listener may nod her head, then keep nodding it because the previous nodding was agreeable. To distinguish the true effect, positive or negative, of what the speaker is saying, an observer would have to eliminate the self-effect of head nodding. Similarly, it's hard to tell if a neuron is exciting or inhibiting another neuron if self-effects cannot be eliminated. If researchers can get a grasp on how crosstalk between neurons produces thoughts, emotions and behavior, the implications could be far-reaching. At the least, medical science would gain an understanding of how people's attitudes and behaviors, as well as brain disorders, develop. Perhaps someday we'll even have "brain chips" to supplement our normal brain activity. If that day ever comes, researchers like Georgopoulos, his University colleagues and others are laying the groundwork today.