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'Smart' mice teach scientists about learning process, brain disorders

behavior might aid in the development of new treatments for these and other conditions, Dr. Bibb said.

The key in this study was being able to "knock out" the gene for Cdk5 only in the brain, and only when the mice were adults. This technique, only recently developed and called conditional knockout, allows much more sophisticated experiments than traditional knockout, which entirely eliminates the gene.

"Being able to turn a gene off throughout a brain is a really advanced thing to do," Dr. Bibb said. "Its been shown that it can be done, but we put the system together and actually applied it."

Normally, Cdk5 works with another enzyme to break up a molecule called NR2B, which is found in nerve-cell membranes and stimulates the cell to fire when a nerve-cell-signaling molecule, or neurotransmitter, binds to it. NR2B previously has been implicated in the early stages of learning.

The new research showed that when Cdk5 is removed from the brain, the levels of NR2B significantly increase, and the mice are primed to learn, Dr. Bibb said.

"We made the animals smarter, but in doing so and applying this technology, we also found biochemical targets that hold promise for future treatments of a variety of cognitive disorders," he said.

The researchers also recorded nerve-cell firings in the hippocampus, an area of the brain associated with learning. Hippocampus slices from the knock-out mice responded much more strongly to an electrical stimulation, supporting the finding that the mice were more prepared to learn.


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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
27-May-2007


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