PKA Dynamics in a Drosophila Learning Center: Coincidence Detection by Rutabaga Adenylyl Cyclase and Spatial Regulation by Dunce Phosphodiesterase

The dynamics of PKA activity in the olfactory learning and memory center, the mushroom bodies (MBs), are still poorly understood. We addressed this issue in vivo using a PKA FRET probe. Application of dopamine, the main neuromodulator involved in aversive learning, resulted in PKA activation specifically in the vertical lobe, whereas octopamine, involved in appetitive learning, stimulated PKA in all MB lobes. Strikingly, MB lobes were homogeneously activated by dopamine in the learning mutant dunce, showing that Dunce phosphodiesterase plays a major role in the spatial regulation of cAMP dynamics. Furthermore, costimulation with acetylcholine and either dopamine or octopamine led to a synergistic activation of PKA in the MBs that depends on Rutabaga adenylyl cyclase. Our results suggest that Rutabaga acts as a coincidence detector and demonstrate the existence of subcellular domains of PKA activity that could underlie the functional specialization of MB lobes in aversive and appetitive learning.

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