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May 18, 1999


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Neurological maps hold key to how brain learns and forgets

BY KRISTIN WEIDENBACH

When the mind forgets, it may not mean the brain has forgotten -- at least that's the case with barn owls. For the wise birds, learning new skills then reverting back to old methods requires nothing more than pulling up the correct neurological map, according to Stanford researchers, who have studied the owls in their quest to find out how the brain learns and forgets.

By outfitting the owls with a pair of prism eyeglasses that give them a skewed view of the world, the scientists have been able to analyze how neurons in the owls' brains adjust to the confusing new environment.

Sight and hearing are intimately connected in barn owls, so in order to adapt completely to the new off-kilter visual world, the animal has to learn new responses to localize the sounds that it hears. It must also forget the old responses that are no longer appropriate, said Eric Knudsen, PhD, Sewall Professor of Neurobiology.

In a series of incremental advances over the last three years, Knudsen and his team have determined how cells in the owl's brain learn to respond correctly to sound. In the May 7 issue of Science, Knudsen and postdoctoral fellow, Weimin Zheng, PhD, now report that they have worked out the opposite side of the equation ­ how cells in the owl's brain forget the incorrect responses.

Barn owls, which have a much more sensitive auditory system than humans or other animals, naturally know how to localize their prey. They quickly locate a chirping cricket or a squeaking mouse by integrating two neurological maps in their brain ­ one based on sound, the other on vision. If the owl first hears a sound in its left ear, it knows it must turn its head to the left to see the noisy critter and scoop it up for lunch. Researchers in Knudsen's lab call the inherent neurological map that the owls use to do this, the normal map.

Owls that are fitted with the prism glasses see a world that is shifted. An owl wearing a pair of right-shifting glasses sees objects to its left when it is looking straight ahead. A young bespectacled owl learns to compensate for this altered perception, turning its head to the right to see what lies straight ahead. These owls have developed a new neurological map that the researchers call the learned map. "For an owl to be able to localize the sound correctly after wearing the prisms it has to be able to forget the older map which is not behaviorally appropriate and follow the new map," said Zheng.

Previous research in the Knudsen lab has shed light on how neurons in the owl's brain learn the new map, but according to Zheng, people knew nothing about the mechanisms underlying the process of forgetting the old map. Zheng and Knudsen focused on the ICX region of the brain, which is a site of auditory learning in the barn owl. This region of the brain is also rich in a certain class of inhibitory nerve cells called GABAergic neurons. The researchers wondered if the normal map, when it was not appropriate to the owl's situation, was being specifically suppressed by these neurons. If their theory was correct, by blocking these neurons the normal map would move to the forefront, replacing the learned map.

Zheng and Knudsen conducted a series of experiments, which confirmed their hypothesis. When the GABAergic neurons were blocked, cells in the owl's brain that had been showing the learned responses suddenly began to show the normal responses. The results were important because they revealed that the normal map had not been lost. The map and all its information had remained intact, but had been temporarily suppressed, or forgotten.

When the researchers tried the same approach on adult owls whose glasses had been removed, they got a very different result. One month after they removed the glasses, they blocked the same neurons in owls that had readjusted to an unadulterated view of the world and were responding normally to sounds using their normal neurological maps. Unlike the unveiling of the normal map in the previous experiment, however, the learned map did not emerge, indicating that it was not being suppressed by the inhibitory action of the GABAergic neurons.

This revealed that the "genetically controlled normal map is different from the learned map controlled by experience," said Zheng.

However, the results presented the researchers with a new conundrum that they are now working to solve. Knudsen and his team knew from their previous work that owls reared with glasses that had subsequently been removed could adapt to the glasses successfully once again if they were reintroduced to the adult owl. These adults quickly remembered how to accommodate the zany view of the world that the glasses induced, whereas adult owls introduced to the glasses for the first time never learned to adapt.

So although the learned map could not be experimentally brought forth by suppression of GABAergic neurons, there must be a trace left in the brain that allows the owls to reacquire it, said Knudsen. Some portion of that circuitry is still there, but like a radio that can be unplugged or have its volume turned all the way down, the signal is not coming through, he explained. Now, the task before Knudsen and his colleagues is to identify the unseen hand that is controlling this phenomenon.

Stanford University School of Medicine, the McKnight Foundation and the National Institutes of Health provided funding for the study. SR