In Brief

In psychology, an experimental setup consisting of a rat, a buzzer and an electrified cage can usually mean only one thing: a rat is about to learn to fear the sound of a buzzer. In an experiment reported in the Nov. 7 issue of Nature, however, that setup--plus a few intracranial electrodes--meant just the opposite.

Gregory Quirk, PhD, and Mohammed Milad of the Ponce School of Medicine in Puerto Rico found that by stimulating neurons in the medial prefrontal cortex, they could prevent rats from freezing in response to a tone--which they had previously learned to associate with a painful shock--and accelerate the process by which they learned that it was no longer dangerous.

The results support the hypothesis, first proposed by Ivan Pavlov in the 1920s, that conditioned responses are never erased, just inhibited by new memories. The findings could also eventually lead to improved treatments for post-traumatic stress disorder (PTSD) and other anxiety disorders.

According to Quirk, the stimulation appears to have mimicked an "all clear" signal that the medial prefrontal cortex emits when it recognizes that a threatening stimulus is actually harmless. The main target of the signal, he says, is probably the amygdala, a brain region important for fear learning that receives strong inhibitory projections from the medial prefrontal cortex. Evidence from this and previous studies suggests that those projections are key to long-term extinction, the process by which a conditioned response to a stimulus is inhibited when the stimulus is no longer associated with rewarding or punishing consequences. "One way to put it is that we're tricking or fooling the brain into thinking the animal went through extinction," says Quirk.

The current study is a long way from clinical applications, but techniques like transcranial magnetic stimulation (TMS), a noninvasive method for activating neurons, might someday be used to stimulate an analogous brain region in humans suffering from PTSD or other anxiety disorders. Current TMS technology might not be able to activate the region, which is buried deep inside the frontal cortex, says Quirk, but the study provides hope that future treatments that trigger the medial prefrontal cortex's "all clear" signal could be effective.