Genetically-Engineered Mice May Hold the Key to Long-Term Memory

Newswise — Mice can be genetically engineered to remember a hidden platform in a water maze for several weeks.

Scientists from the Blanchette Rockefeller Neurosciences Institute (BRNI) have located a gene that is a powerful regulator of long-term memory, according to a research article - Enhancement of long-term memory retention and short-term synaptic plasticity in cbl-b null mice - that will appear in the March 28 issue of the Proceedings of the National Academy of Sciences.

The article can be accessed online at: http://www.pnas.org/cgi/reprint/0601043103v1.pdf

Daniel L. Alkon, M.D., is scientific director of BRNI and is a co-author of the article along with Dr. Dong-Ping Tan. According to Dr. Alkon, the mice were genetically engineered to remove the cbl-b gene. They also discovered that this gene controls enhancement of synaptic signaling in the brain.

The research compared the abilities of genetically engineered mice to the abilities of normal mice to locate a hidden platform in a water maze. "In normal mice, there was no measurable long-term memory for this particular water maze task," Alkon said. "However, the mice without this gene were able to remember the water maze six weeks later, a very long time for a mouse."

This finding is of particular interest to Alzheimer's researchers, Alkon said, because it provides an important opportunity to trace the molecular pathways for long-term memory and the critical physiological changes that play a role in its formation. "We can now begin to see what molecular changes this gene controls, and how these molecular changes affect the physiology of the brain."

"Alzheimer's disease affects the brain's ability to transfer short-term memories into long-term memories," he continued. "This research leads us to new targets for research, and potential new targets for Alzheimer's disease drug therapy."

The next step in capitalizing on this discovery, Alkon said, will be to screen for genomic and proteomic changes in the brain that are regulated by this gene. "In this animal model, the molecular changes were also accompanied by robust synaptic changes in the animal's brain. These synaptic changes also appear to be critical for long-term memory formation."

BRNI's primary mission is to accelerate the transfer of neurological discoveries from the lab, including diagnostic tools and treatments, directly to patients who are suffering from neurological diseases such as Alzheimer's. Sen. Jay Rockefeller of West Virginia founded the institute in memory of his mother, who died of Alzheimer's disease.

"We can now begin to really study new molecular and synaptic targets in the brain," Alkon said. "This is a step forward in our quest to understand and ultimately defeat Alzheimer's and other diseases of the mind."