A role for prefrontal cortex in memory storage for trace fear conditioning.

The prefrontal cortex has been shown to participate in the association of events separated by time. However, it is not known whether the prefrontal cortex stores the memory for these relationships. Trace conditioning is a form of classical conditioning in which a time gap separates the conditioned stimulus (CS) from the unconditioned stimulus (US), the association of which has been shown to depend on prefrontal activity. Here we demonstrate that inhibition of extracellular signal-regulated kinase (Erk) cascade (a biochemical pathway involved in long-term memory storage) in the rat medial prefrontal cortex did not interfere with memory encoding for trace fear conditioning but impaired memory retention. In addition, animals displayed impaired memory for the irrelevancy of the training context. Hippocampal Erk phosphorylation was found to have a later time course than prefrontal Erk phosphorylation after trace fear conditioning, indicating a direct role for the prefrontal cortex in associative memory storage for temporally separated events as well as in memory storage of relevancy.