Null EPAC mutants reveal a sequential order of versatile cAMP effects during aversive odor learning.

Here, we define a role of the cAMP intermediate EPAC in aversive odor learning by means of null epac mutants. Complementation analysis revealed that EPAC acts downstream from the adenylyl cyclase and in parallel to protein kinase A. By means of targeted knockdown and genetic rescue we identified mushroom body Kenyon cells (KCs) as a necessary and sufficient site of EPAC action. We provide mechanistic insights by analyzing acquisition dynamics and using the "performance increment" as a means to access the trial-based sequential organization of odor learning. Thereby we show that versatile cAMP-dependent mechanisms are engaged within a sequential order that correlate to individual trials of the training session.