Genetic tags reveal secrets of memories' staying power in mice

Newly synthesized AMPA glutamate receptors (green) were captured by mushroom-shaped spines in mouse hippocampus neurons encoding memory, after one (left), two (middle) and six (right) hours of fear conditioning. The... Click here for more information.

A better understanding of how memory works is emerging from a newfound ability to link a learning experience in a mouse to consequent changes in the inner workings of its neurons. Researchers, supported in part by the National Institutes of Health's National Institute of Mental Health (NIMH), have developed a way to pinpoint the specific cellular components that sustain a specific memory in genetically-engineered mice.

"Remarkably, this research demonstrates a way to untangle precisely which cells and connections are activated by a particular memory," said NIMH Director Thomas Insel, M.D. "We are actually learning the molecular basis of learning and memory."

For a memory to last long-term, the neural connections holding it need to be strengthened by incorporating new proteins triggered by the learning. Yet, it's been a mystery how these new proteins -- born deep inside a neuron -- end up becoming part of the specific connections in far-off neuronal extensions that encode that memory.

By tracing the destinations of such migrating proteins, the researchers located the neural connections, called synapses, holding a specific fear memory. In the process, they discovered these synapses are distinguished by telltale molecular tags that enable them to capture the memory-sustaining proteins.

Mark Mayford, Ph.D., and Naoki Matsuo, Ph.D., of the Scripps Research Institute, report on their findings in the February 22, 2008, issue of the journal Science.