Dallas research finds gene possibly linked to memory

Monday, June 26th 2000, 12:00 am
By: News On 6

Life would be difficult without memories. And memories might be difficult without a gene called NPAS2, Dallas scientists say.

Local researchers have found that without this gene, mice have trouble learning how to know when something scary is about to happen. That's important for mice to survive out in the wilderness, or even under the kitchen counter.

And for scientists, the gene's connection to memory is an opportunity to study how the brain takes in information and stores it for future use.

"It's a tantalizing beginning," said Eric Kandel, a neuroscientist from Columbia University in New York. "It whets one's appetite for more."

Researchers from the University of Texas Southwestern Medical Center at Dallas reported the discovery in the latest issue of the journal Science.

They noted that the gene may also be connected to the body's internal clock that keeps track of day and night.

"There might be rhythmicity in the brain that might be important for optimal ... functioning," said Dr. Joseph Garcia of UT Southwestern.

Before the new study, scientists already knew that the NPAS2 gene was active only in the brain, where it orchestrates production of a special protein molecule. That protein's job, scientists believe, is to act as a coach, spurring other genes into action.

But to really understand what NPAS2 does in the brain, the researchers wanted to see how mice would fare when the gene was disabled. So using the tricks of genetic engineering, the UT Southwestern scientists made mice with a malfunctioning NPAS2 gene. Because the gene was known to work in the brain, the researchers tested the mice's mental abilities.

The mice, Dr. Garcia said, went through a battery of tests and did well on all of them, with one exception. The test required mice to learn that a staticlike noise signaled an impending mild electrical shock to their feet. Mice without the gene had more trouble on the test. So it seems, Dr. Garcia said, that the mice need that gene to remember certain emotional events.

Other scientists said it was hard to know what to make of the findings.

Dr. Kandel noted that while the mice did worse on one test, they didn't fail it outright.

"That is not a whopping change," he said.

More research is needed to understand exactly how the gene helps the brain work.

"We don't have a sense of how it fits into other molecules that might be important in memory," Dr. Kandel said.

One way the gene may fit in with other brain molecules is through a connection with an internal biological clock, said Steven McKnight, another UT Southwestern scientist involved in the study. NPAS2 has all the telltale signs of fitting into the network of proteins and genes that help organisms keep track of day and night.

These internal timekeepers, known as circadian clocks, control body temperature, blood pressure and other biological processes that change on a 24-hour cycle. In recent years, scientists have found many "cogs" and "gears" of these clocks in a variety of organisms.

The protein produced by the NPAS2 gene looks a lot like one of the clock proteins, Dr. McKnight said, and more studies are being done to find out how the gene behaves during the day-night cycle.

For now, the scientists are speculating that NPAS2 somehow changes nerve cells as day turns to night and again when night yields to day. Without the NPAS2 gene, that natural cycling may be disrupted, he said. That may explain why the brain is generally sharper during the day than at night.

"If you don't have that nice cyclic pattern, and are not getting appropriate rest, then the alert phase will simply be less alert," Dr. McKnight said.

Other scientists participating in the research were UT Southwestern's Di Zhang, Sandi Jo Estill, Carolyn Michnoff, Jared Rutter, Martin Reick, Kristin Scott and Ramon Diaz-Arrastia.