The PDE4D ortholog Dunce suppresses memory in Drosophila melanogaster

The regulation of cAMP concentration is a key component of the mechanisms underlying learning and memory. In Drosophila melanogaster , the cAMP-specific phosphodiesterase mutant dunce 1 results in increased levels of cAMP but poorer associative short-term memory and anesthesia-resistant memory. This raises the question of how elevated cAMP levels can cause defects in both short-term and long-term memory. To answer this question, we analyzed associative olfactory learning and memory in Drosophila larvae of both sexes with the isoform-specific dunce Δ143 mutation. Flies with this mutation exhibited better learning than flies with the dunce 1 mutant. The memory facilitated by dunce Δ143 was stable and easily reversable. The improvement in memory was also traced to a defined subset of neurons. A comparison of the subcellular localization of Dunce isoforms indicates that the regulation of cAMP in the soma suppresses early memory formation. We revealed that Dunce regulates at least two different aspects of learning and memory, specifically, preventing the premature formation of memory and facilitating the formation of memory after multiple training sessions. The different functions of Dunce might be due to different cell types. Significance Statement In model systems such as Aplysia and mice, elevated cAMP levels are associated with increased learning and memory performance; in contrast, Drosophila dunce mutants with elevated cAMP levels exhibit memory decline. Here, we revisited the function of the phosphodiesterase 4D ortholog Dunce and showed that Dunce both promotes and inhibits memory formation.