Signaling at A-kinase anchoring proteins organizes anesthesia-sensitive memory in Drosophila.

The ubiquitous cAMP-protein kinase A (PKA) signaling pathway exhibits complex temporal requirements during the time course of associative memory processing. This directly raises questions about the molecular mechanisms that provide signaling specificity to this pathway. Here, we use Drosophila olfactory conditioning to show that divergent cAMP signaling is mediated by functionally distinct pools of PKA. One particular pool is organized via the PKA regulatory type II subunit at the level of A-kinase anchoring proteins (AKAPs), a family of scaffolding proteins that provides focal points of spatiotemporal signal integration. This AKAP-bound pool of PKA is acting within neurons of the mushroom bodies to support a late phase of aversive memory. The requirement for AKAP-bound PKA signaling is limited to aversive memory, but dispensable during appetitive memory. This finding suggests the existence of additional mechanisms to support divergence within the cAMP-PKA signaling pathway during memory processing. Together, our results show that subcellular organization of signaling components plays a key role in memory processing.