Yi Zuo, a neurobiologist at UC Santa Cruz, has discovered how learning and memory imprint their effects on the brain - spurred by inspiration from her father, her 3-year-old son and a family friend who suffered a stroke.

The intersection of those three people led to a long series of experiments with more than 200 smart and frisky laboratory mice that revealed that learning new tasks can permanently alter the brain's nerve cells in animals, and perhaps in humans.

In a recent visit to her lab among the towering redwoods on the Santa Cruz campus, Zuo explained that her lab mice have shown her and her research team that in learning a new task, the connections between specific cells in the brain are swiftly rewired, and that those fresh connections can become permanent - even after the mice learn even newer tasks.

Much the same must be true in humans, she concluded.

"When you learn to ride a bicycle," Zuo said, "you may fall off a few times, but once you've learned how, you never, never forget."

In other words, the new connections - known as synapses - remain fixed.

Important and helpful study

The findings were published recently in the on-line journal Nature, and Eric Kandel, a Columbia University neurologist and psychiatrist who won the Nobel Prize for discovering how memories are stored in the brain's nerve cells, called Zuo's work "interesting and important."

John Krakauer, another Columbia neurologist who specializes in learning and memory after strokes, said the Zuo group's report on memory in mice shows clearly how learning can affect structural changes in the brain - a question that should be helpful in studying the problem in stroke patients, he said.

The road that led to the research began three years ago when Zuo's father, a physician in Beijing, told her that her laboratory brain research in Santa Cruz was "too basic" and she should do something "more useful" related directly to medical problems.

At the same time, Zuo learned that a family friend was recovering from a stroke - an event that often leads to memory loss.

"That really gave me the idea of doing stroke-related research," she said. "And at the same time I also got interested in how we learn, because my son was 3 years old.

"Together these gave me the idea of working on what we call motor learning during early human development, and rehabilitation in the brain after a stroke."

In the lab, she and her lab colleagues used some tricky, but harmless techniques available to brain researchers who study mice as models for the human condition.

They patiently trained scores of the mice, one at a time, to put a foreleg through a slot in a transparent plastic box, and to grab a single speck of delicious birdseed no bigger than a pinhead.

Some of the mice they trained were only a few days old, while others were teenagers and adults.

Rewiring in under an hour

After training, the scientists took high-tech movies of the living animals' brains - a procedure possible because the mice were genetically bred so their brain cell connections would show up on film glowing from fluorescence after each training exercise. It was painless to the mice.

The synapses are formed by other tiny brain structures called dendritic spines. And in the lab, Zuo and her colleagues found that those microscopic spines not only rewired the connections in less than an hour after the mice were trained, but then remained stable permanently.

To prove that stability, the mice were later trained to perform a different task. The reward wasn't birdseed, but slender strands of capellini pasta. After learning the new task, the mice were challenged again with the original birdseed task, and they performed almost flawlessly - proof that they hadn't forgotten, Zuo said. And a second set of movies of their brains showed that the earlier rewired synapses and dendritic spines had remained intact, Zuo and her colleagues found.

Zuo's major colleagues in the work were Tonghui Xu, a postdoctoral researcher in her lab, and Xinzhu Yu, a doctoral student there.