Distinct prefrontal molecular mechanisms for information storage lasting seconds versus minutes.

The prefrontal cortex (PFC) is known to actively hold information "online" for a period of seconds in working memory for guiding goal-directed behavior. It has been proposed that relevant information is stored in other brain regions, which is retrieved and held in working memory for subsequent assimilation by the PFC in order to guide behavior. It is uncertain whether PFC stores information outside the temporal limits of working memory. Here, we demonstrate that although enhanced cAMP-dependent protein kinase A (PKA) activity in the PFC is detrimental to working memory, it is required for performance in tasks involving conflicting representations when memory storage is needed for minutes. This study indicates that distinct molecular mechanisms within the PFC underlie information storage for seconds (working memory) and for minutes (short-term memory). In addition, our results demonstrate that short-term memory storage within the prefrontal cortex is required for guiding behavior in tasks with conflicts and provides a plausible mechanism by which the prefrontal cortex executes cognitive control.