A compound given at just the right time may make mice forget to be afraid.

The amygdala, shown here in red, is the area of the brain that learns fear.

The ultimate memory eraser—a way to avoid posttraumatic stress disorder—is now a reality for mice. HHMI investigator Richard Huganir has discovered a protein critical for erasing memory of a traumatic event.

When the brain learns something—a new skill or a fear response, for example—neurons gain surface receptors at synaptic connections that strengthen signals from neighboring neurons. When fear is learned, this strengthening happens in an area of the brain known as the lateral amygdala.

To find a way to block this memory formation, Huganir and collaborators at the Johns Hopkins University School of Medicine imparted fear in mice by giving them a mild shock while playing a specific tone. When the mice heard the tone again—for weeks afterward—they froze.

The researchers examined the animals' brains at various times postshock. After a few hours, the number of glutamate receptors—common in neuron signaling—had increased at synapses in the lateral amygdala. Twenty-four hours later though, most of these receptors had lost a subunit, turning them into more rare calcium-penetrable AMPA receptors (CP-AMPARs). This finding was a surprise, especially since, a few days later, the receptors regained the subunit, returning to the more common form.

The team discovered that as CP-AMPARs the receptors are especially unstable and can be selectively removed from synapses by activation of another brain receptor, mGluR1. They hypothesized that removing CP-AMPARs at just the right time could prevent the memory linking the tone and the shock. The receptors' rarity meant that other parts of the brain wouldn't be affected.

Their hypothesis was right; a behavioral therapy known to activate the mGluR1 pathway removed these rare receptors and erased the fear memory. Now, the researchers are working to develop drugs that could activate mGluR1 to erase the memory in place of behavioral therapy. The only caveat: the compound would have to be administered in a brief window of time after the event, when CP-AMPARs are present.

Huganir thinks the results, published in Science on November 18, 2010, will likely translate to humans. If so, there might be a period of time after a traumatic event when the brain can be coaxed to forget about it.

Photo: Living Art Enterprises / Photo Researchers, Inc.