Phosphorylation of Glutamate Receptors Critical to Memory Storage

Researchers have genetically engineered a line of mice that are unable to phosphorylate receptors for glutamate molecules in the brain, which resulted in animals with defective mechanisms for storing spatial memories. Their work was reported in the March 7, 2003, issue of Cell.

Mice unable to phosphorylate the GluR1 subunit of the glutamate receptor learned to find a hidden platform in a pool of water as well as normal mice, but could not remember its position eight hours later. In contrast, normal mice remembered what they had learned even after 24 hours.

"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,” explained senior author Dr. Richard Huganir, professor of neuroscience in the Johns Hopkins School of Medicine's Institute for Basic Biomedical Sciences (Baltimore, MD, USA; www.jhu.edu). "This new work shows that phosphorylation of this target protein does indeed affect an animal's ability to remember.”

"We have established that the two phosphorylation sites on GluR1 are crucial for retention of spatial learning, but it is likely that other sites in other subunits of this glutamate receptor will also play a role,” said Dr. Huganir.



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