( Mice genetically engineered to lack a ...)'Smart' mice teach scientists about learning process, brain disorders

Mice genetically engineered to lack a single enzyme in their brains are more adept at learning than their normal cousins, and are quicker to figure out that their environment has changed, a team led by researchers at UT Southwestern Medical Center has found.

The results, appearing today in the online edition of the journal Nature Neuroscience, reveal a new mechanism of learning in the brain, which might serve in humans as a target for treating disorders such as post-traumatic stress disorder, Alzheimer’s disease or drug addiction, the researchers said.

"It’s pretty rare that you make mice ‘smarter,’ so there are a lot of cognitive implications," said Dr. James Bibb, assistant professor of psychiatry and the study’s senior author.

"Everything is more meaningful to these mice," he said. "The increase in sensitivity to their surroundings seems to have made them smarter."

The engineered mice were more adept at learning to navigate a water maze and remembering that being in a certain box involves a mild shock. Equally important, Dr. Bibb said, when a situtation changed, such as the water maze being rearranged, the engineered mice were much faster to realize that things were different and work out the new route.

Dr. Bibb cautioned that while the mice learn faster, studies on the long-term effects of deleting the enzyme, called Cdk5, from the brain are continuing.

The group is also beginning a search for drugs that might create the same effects without genetic manipulation and monitoring the animals’ health and behavior over time.

The findings may have applications in treating post-traumatic stress disorder, where getting a patient to learn that a once-threatening situation no longer poses a danger is a major goal.

In addition, Cdk5 is heavily implicated in Alzheimer’s disease and addiction to drugs of abuse, so understanding how the enzyme affects the brain and behavior might aid
'"/>

Source:UT Southwestern Medical Center