Hasselmann, T. | bioRxiv Science

bioRxiv2025

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 dunce1 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{Delta}143 mutation. Flies with this mutation exhibited better learning than flies with the dunce1 mutant. The memory facilitated by dunce{Delta}143 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 StatementIn 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.

neuroscience↗

bioRxiv2022

Population-specific association of Clock gene polymorphism with annual cycle timing in stonechats

Timing is essential for survival and reproduction of organisms across the tree of life. The core circadian clock gene Clk has been implicated in annual timing and shows highly conserved sequence homology across vertebrates except for one variable region of poly Glutamine repeats. Clk genotype varies in some species with latitude, seasonal timing and migration. However, findings are inconsistent, difficult to disentangle from environmental responses, and biased towards high latitudes. Here we combine field data with a common-garden set up to study associations of Clk with latitude, migration and annual-cycle timing within the stonechat species complex with trans-equatorial distribution range. Including 950 individuals from nine populations with diverse migratory strategies. Gene diversity was lowest in resident African and Canary Island populations and increased with latitude, independently of migration distance. Repeat length and annual-cycle timing was linked in a population-specific way. Specifically, equatorial African stonechats showed delayed timing with longer repeat length for all annual-cycle stages. Our data suggest that at low latitudes with constant photoperiod, Clk genotype might orchestrate a range of consistent, individual chronotypes. In contrast, the influence of Clk on annual-cycle timing at higher latitudes might be mediated by its interactions with genes involved in (circadian) photoperiodic pathways.

genetics↗