Revisiting the role of cAMP in Drosophila aversive olfactory memory formation

In Drosophila melanogaster, odor stimulation elevates cAMP broadly across Kenyon cell axons, so CS+ responsive neurons cannot be distinguished from others by bulk cAMP levels.

• Why it matters: The Rutabaga coincidence-detection model predicts that CS+ neurons should be selectively marked by higher cAMP, but this key assumption lacked direct live-imaging support.
• What they did: Live imaging showed olfactory-evoked dopamine signaling and widespread cAMP increases with only weak spatial overlap with local Ca2+ responses; conditioning then reshaped compartmental cAMP patterns and their inverse relationship with acetylcholine.
• The result: Conditioning altered dopamine responses to CS+ and established an inverse cAMP–ACh relationship for CS+ but not CS-, absent in rutabaga mutants; pharmacologically elevating cAMP suppressed KC ACh release, implicating cAMP-dependent ACh suppression in aversive memory formation.

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