Molecular mechanism for learning and memory is identified

EVANSTON, Ill. -- In a study to be published in the June 20 issue of the Proceedings of the National Academy of Sciences, researchers at Northwestern University report new insights into the biological and molecular underpinnings of learning and memory.

Past research has shown that a growth-associated protein, called GAP-43, that is found in neurons and no other organ of the body, is required for the growth of nerve cell processes during the brain's early development and later during neuronal regeneration. What was not known was whether or not GAP-43 could alter axonal growth and synaptic change, elements crucial to learning and memory.

Now, a research team led by Aryeh Routtenberg, professor of psychology, neurobiology and physiology, has demonstrated that GAP-43, when overexpressed in a phosphorylatable form, enhances learning and memory in the mammalian brain. The findings could provide a novel target for new drugs to combat memory loss and learning disorders.

"This is the first evidence that demonstrates that GAP-43 does indeed regulate learning," said Routtenberg. "It does so by accelerating the rate at which learning occurs. Our findings specify the particular sequence of chemical reactions that are involved in the process of storing information."

Routtenberg and his team have demonstrated that genetically engineered mice that have more phosphorylatable GAP-43 in their brains learn tasks more quickly and can forget one strategy in order to learn a diametrically opposed strategy. Experiments also showed that mice overexpressing a form of GAP-43 that could not be phosphorylated had no learning enhancement.

Phosphorylation is a fundamental molecular process in which a phosphate is transferred to a protein, causing the protein to change shape and function. In the case of GAP-43, the protein kinase C (PKC) is the enzyme responsible for its phosphorylation.

The researchers first studied four different types of mice and their

Contact: Megan Fellman
Northwestern University

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