The experiments are believed to be the first to prove that subtly altering the chemistry of a certain protein can profoundly affect a brain cell's ability to respond to external stimulation, a process called neuronal plasticity, long thought to underlie learning and memory.
By genetically altering part of a receptor that binds glutamate -- the most important excitatory chemical in the brain -- the scientists created a version of the protein that could not be modified by adding phosphate groups. In their experiments, preventing phosphorylation of the receptor kept it from responding normally to external stimulation in the lab and limited how long animals could store new memories.
"Since 1986, phosphorylation has been recognized as a key to modulating receptor responses to neurotransmitters like glutamate, but this is the first demonstration that phosphorylation of a particular target protein mediates the processes we believe are behind learning and memory," says Richard Huganir, Ph.D., professor of neuroscience in the Johns Hopkins School of Medicine's Institute for Basic Biomedical Sciences. "This new work shows that phosphorylation of this target protein does indeed affect an animal's ability to remember."
Mice with the "phosphate-free" version of the protein, known as GluR1, learned to find a hidden platform in a pool of water as well as normal mice, but couldn't remember its position eight hours later, the researchers report. In contrast, normal mice remembered what they'd learned even after 24 hours.