A conserved role for sleep in supporting spatial learning in Drosophila

Abstract

Sleep loss and aging impair hippocampus-dependent spatial learning in mammalian systems.Here we use the fly Drosophila melanogaster to investigate the relationship between sleep and spatial learning in healthy and impaired flies. The spatial learning assay is modeled after the Morris Water Maze. The assay uses a 'thermal maze' consisting of a 5X5 grid of Peltier plates maintained at 36-37C and a visual panorama. The first trial begins when a single tile that is associated with a specific visual cue is cooled to 25°C. For subsequent trials, the cold tile is heated, the visual panorama is rotated and the flies must find the new cold-tile by remembering its association with the visual cue. Significant learning was observed with two different wild-type strains -Cs and 2U, validating our design. Sleep deprivation prior to training impaired spatial learning. Learning was also impaired in the classic learning mutant rutabaga (rut); enhancing sleep restored learning to rut mutants. Further we found that flies exhibited dramatic age-dependent cognitive decline in spatial learning starting at 20-24 days of age.These impairments could be reversed by enhancing sleep. Finally, we find that spatial learning requires dopaminergic signaling and that enhancing dopaminergic signaling in aged flies restored learning. Our results are consistent with the impairments seen in rodents and humans.These results thus demonstrate a critical conserved role for sleep in supporting spatial learning, and suggest potential avenues for therapeutic intervention during aging. STATEMENT OF SIGNIFICANCEWe have studied the relationship between sleep and plasticity using a Drosophila learning assay modified after the Morris Water Maze. Using this assay, we find that sleep loss impairs spatial learning. As in mammals, flies exhibited age-dependent spatial learning impairments.Importantly, the age-dependent impairments were reversed by enhancing sleep. Interestingly, our results mirror studies on hippocampus dependent memories in rodents and humans. Thus, our data describe an evolutionarily conserved role for sleep in regulating spatial learning. They also support augmenting sleep as a therapeutic strategy to ameliorate learning impairments.

A connectome of theDrosophilacentral complex reveals network motifs suitable for flexible navigation and context-dependent action selection

“…Summary: vector computations in the FB The discussion above supports the notion that the FB network has the computational capacity to compute, store, and read out vectors in support of goal-directed navigational behaviors. While we have focused on path integration as a canonical vector-based computation, Drosophila are known to perform several other behaviors that may rely on the formation of goal vectors, including: local search, a path-integration-based foraging strategy (Corrales-Carvajal et al, 2016;Dethier, 1957;Kim and Dickinson, 2017); menotaxis, where a constant heading is maintained relative to an arbitrary goal direction to generate straight trajectories that support long-distance dispersal (Giraldo et al, 2018;Green et al, 2019;Leitch et al, 2020); place learning, which requires associating visual cues with the presence of a cool spot in an otherwise hot 2D environment (Melnattur et al, 2020;Ofstad et al, 2011); and the detour paradigm, where flies orient towards directions associated with attractive landmarks even after they have disappeared (Neuser et al, 2008). In addition, ethologically-based studies in behaving insects have established a range of vector-based behaviors, from long distance migrations that require a time-compensated sun compass (Heinze and Reppert, 2011;Perez et al, 1997) to the waggle dance that bees use to communicate the distance and direction of a food source (Frisch, 1967).…”

Characterization of sleep‐related neurochemicals at different developmental stages and insomnia models of Drosophila melanogaster

“…Fortunately, it is these features that promote the development of sleep in the Drosophila model. The age‐dependent cognitive decline in spatial learning was studied in flies of different ages, and it was found that enhanced sleep can reverse learning impairment concurrent with DA intervention (Melnattur et al, 2021). In addition, in the caffeine‐induced sleepless Drosophila model, increasing the synthesis of GABA could improve sleep behaviour and the improvement depended on elevating the expression of GABA receptors (Jo, 2018).…”