查看文章

In the olfactory aversive conditioning of Drosophila melanogaster, an odor, the conditioned stimulus (CS), is associated with electric shock, the unconditioned stimulus (US). The Rutabaga adenylyl cyclase in Kenyon cells (KCs) of the fly brain synthesizes cAMP, which is believed to serve as the coincidence detector synergistically stimulated by calcium/calmodulin evoked by the odor reception and GαS released in response to the dopamine signaling elicited by electric shock. However, live imaging analyses revealed that olfactory stimulation itself elicited the activation of dopaminergic neurons and resulted in the elevation of cAMP levels in KCs that received dopamine, regardless of calcium signaling. This finding raises questions about the longstanding and fundamental comprehension of conditioning mechanisms, as the cAMP levels in CS+ KCs could not be distinguished from those in the rest of the KCs. Our data indicate that the cAMP level is an unlikely candidate for serving as a memory engram. Furthermore, our findings demonstrate that cAMP has an adverse impact on the release of acetylcholine from KCs. Accordingly, we postulate that, during conditioning, cAMP depresses KCs, thereby skewing the valence of the CS+ odor towards a more aversive state for the conditioned flies, ultimately culminating in the formation of aversive memories.