ERK2 and CREB activation in the amygdala when an event is remembered as “Fearful” and not when it is remembered as “Instructive”

A training protocol was developed based on durable exposure to the two‐way shuttle avoidance task, in which the conditioned stimulus (CS), which was fear evoking for both training conditions on the first day of training, becomes instructive at the end of training under controllable conditions but remains fear evoking under the uncontrollable conditions. The protocol was utilized to examine whether, depending on the training regime, the memory formed will result in a different level of involvement of the amygdala. Three groups of rats were tested: controllable, subjected to durable avoidance learning; uncontrollable, subjected to the same training schedule but with no control over the stressor; and naïve. Two weeks later, after the introduction of a reminder cue, freezing response, defecation, and blood corticosterone (CORT) of the uncontrollable group were higher than in the controllable and naïve groups, indicating that indeed, for this group, the CS remained fear evoking. Significantly higher than chance shuttling responses of the controllable group indicated that, for them, the CS became ”instructive.” Activation of ERK2 and CREB in the basolateral amygdala (BLA) was highest in the uncontrollable group compared with the controllable and naïve groups. Overall, the results indicate that the training procedure succeeded in dissociating between the physical (electric shock) and the psychological (control) attributes of the experience. Also, our findings support the view that an emotionally charged reminder cue activates the amygdala but that, as a previously fear‐evoking memory cue becomes instructive, the involvement of the amygdale lessens. © 2009 Wiley‐Liss, Inc.