GMO Mice Shed Light on Learning, Memory

Dr. Joe Z. Tsien at the Medical College of Georgia has been running experiments that help explain the neurological processes involved in memory and learning within the brain.

“We have been able to identify very critical memory genes and manipulate them in such a way that we can either turn them off, so the memory of mice is impaired, or enhance them.”
He’s talking about Doogie, a mouse that over-expresses a “smart” gene in the hippocampus, a portion of the brain critical to memory and attacked by Alzheimer’s. NMDA receptors are essentially small pores on cell membranes that let ions in and increase neuronal activity and communication. Younger people have higher amounts of a NMDA subunit, NR2B, that keeps communication channels open longer so more information is shared. As people age, they switch to subunit NR2A, presumably because evolution has figured out by then we should have transmitted our genes to offspring, he says. Dr. Tsien and his colleagues made Doogie by over-expressing the NR2B gene and a conditional knockout by eliminating another NMDA receptor subunit.
Doogie was better at remembering and putting things in context, able to quickly recognize something he had seen before and move on to explore something new. He made the cover of Time magazine in 1999 and was one of Science magazines top-10 scientific breakthroughs that year. The “dumb” mouse, on the other hand, couldn’t find his way out of a maze.
Dr. Tsien also has found that intelligence requires teamwork, that neurons work in cliques not only to remember specifics but also to generalize knowledge, which essentially defines intelligence.
To get a good handle on the extent of simultaneous neuronal activity, he and his former postdoctoral fellow, Dr. Longnian Lin, first developed a technique to record the activity of up to 200 mouse neurons, rather than the 20 to 30 previously possible. They then identified a small number of neurons in the hippocampus of a mouse that consistently respond to the concept of a bed or nest. Make that nest inaccessible by covering it with glass, for example, and the cells and mouse become disinterested, they showed in research published March 2007 in Proceedings of the National Academy of Sciences.
“Intelligence is really built on memory, your experiences from the past, translating that into guidelines so when you seen a new situation, you know what you need to do,” says Dr. Tsien, whose collective contributions to learning and memory were featured on the July 2007 cover of Scientific American. “That helps us not only recognize our bed, for example, but to generally understand what a bed is and to know one when we see it. You check into a hotel, you know where to sleep. When you come to my office, you know where to sit. You don’t sit in the floor or on my table. You sit on the chair. The chair may not be exactly like one you have seen before, but you know it’s a chair. That is a basic form of intelligence.”

Press release: Brain scientist shedding light on learning, memory
Image credit: Wellcome Images: Dorsal Root Ganglion neuron growth cones