Be smart

It hurts to be smart. That's one conclusion from the latest study of so-called Doogie mice - "smart" rodents that are genetically engineered to have enhanced memory and learning skills.

Along with those extra IQ points, researchers have found, comes an added sensitivity to pain. The new work offers a sobering lesson about the difficulty of enhancing certain brain functions without simultaneously taking a toll on others. It might temper any momentum to engineering genetic enhancements into people. Doogie mice, named after the main character in the television show Doogie Howser, MD, made a big splash when they were introduced to the world in September 1999.

Having been endowed with extra copies of a gene involved in memory formation, the animals outperformed their normal counterparts on a variety of tasks.

They were better at recognising objects they had seen before, remembered painful experiences longer and recalled with greater accuracy the location of submerged platforms in milky water.

Some scientists sniffed at the suggestion that the mice were brainy, noting intelligence was much more than a collection of four or five mental skills.

Nonetheless, the work was the first to show that, by adding a few extra copies of a single gene to an embryo, researchers improved an animal's performance on a range of memory and learning tasks.

Some suggested drugs designed to mimic the gene's effects might help Alzheimer's patients. The new work hints it won't be that easy.

Min Zhou and his colleagues at Washington University School of Medicine in St Louis assessed how Doogie mice responded to tissue damage and inflammation.

They suspected that pain caused by those types of injury might be controlled by the same "NR2B receptor" Doogie mice are overendowed with and that gives them their superior memories.

NR2B receptors are proteins that act as "coincidence detectors" in the brain. They recognise, for example, when a certain sound is linked to the arrival of food and help consolidate such coincidences into learnt associations.

The researchers subjected the mice to stimuli that caused either short-term or long-term pain.

They heated the animals' tails, poked their foot pads with stiff fibres and injected their paws with irritating solutions. Then they used neurological tests to see how the animals' brains responded and tracked their behavior.

Those tests indicated that, compared with normal mice, Doogie mice were equally sensitive to short-term pain. But chronic inflammatory pain, such as that caused by the injected irritants, lasted longer in Doogie mice.

"Our results suggest that a genetic manipulation conferring enhanced cognitive abilities may also provide unintended traits, such as increased susceptibility to persistent pain," the team reports in yesterday's issue of the journal Nature Neuroscience.

Joe Tsien, the Princeton scientist who led the creation of Doogie mice, said he wasn't convinced the mice felt more pain.

But several scientists said the new study offered strong substantiation that a Doogie mouse's pain was real.

"This is very convincing evidence" that the mice had prolonged chronic pain responses, said James L. McGaugh, a neuroscientist at the University of California at Irvine.

"Most of our brain regions are multipurpose. These things are all intertwined," he said.


Newly generated neurons help form new memories.

Contrary to long-held popular belief, our brains may not only produce new brain cells or neurons throughout life, but the newly generated neurons quickly become involved in the formation of new memories a fact that may have positive implications for the recuperative powers of our own brains when damaged by stroke or other disease or trauma.

In a study published today in the March 15 issue of the journal Nature, Rutgers psychology professor Tracey J. Shors and Princeton psychology professor Elizabeth Gould found that newly generated neurons in the hippocampus area of animal brains help form new memories.

Despite what is generally believed, scientists in recent years have learned that the brains of vertebrate animals, a category ranging from amphibians to humans, continue to produce new neurons throughout life. What was not known was whether the newly generated cells are actively involved in memory formation.

To find out, Shors and Gould studied the thousands of neurons produced daily in the hippocampus area of rat brains, an area that controls a form of memory known as trace conditioning, in which the animal must learn to associate stimuli that are separated in time. The researchers discovered that when they reduced the production of new hippocampus cells via a drug inhibitor, the rats were no longer able to form certain types of new memories.

This occurred even though mature hippocampus neurons remained functionally intact. On the other hand, when the researchers stopped administering the drug inhibitor, thus restoring the hippocampus area's ability to generate new cells, the ability to acquire trace memories was also restored.

"It appears that the new neurons become involved in memory about a week to two weeks after they are generated and they are involved in memories normally handled by the hippocampus," says Shors.

The team also noted that the reduction of new hippocampal cells had no apparent effect on memory that depends on other parts of the brain.

Although the researchers studied only the hippocampus, their research implies that the brain's recuperative powers may be far greater than previously thought. "We've known for some time that the brain generates new cells throughout life," says Shors. "These results suggest that one of the functions of these new cells is related to the process of memory formation."

In an earlier study, the two researchers demonstrated the nostrum, "use it or lose it." In the earlier study of rat brains, they found that while most new brain cells die within weeks of their generation, putting them to work through hippocampal-related learning improved their survival rate.

Rutgers, The State University Of New Jersey