A conserved role for sleep in supporting Spatial Learning in Drosophila

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 5 × 5 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 a 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

Novel developmental functions of the Drosophila SOX gene Dichaete

All multicellular life begins as a single cell—the fertilised egg, from which the adult organism develops. As a general priniciple, as embryos progess through development, changes in cellular status seem to be effected by cell specific transcription factors which regulate specific gene subsets. The SOX (Sry box) family of transcription factors are one such developmentally important class of transcription factors, consisting of twenty mammalian proteins that each contain a single High Mobility Group (HMG) DNA binding domain that is \u3e50% homologous to that of Sry, the mammalian testes determining factor. SOX proteins are multi-functional developmental regulators that sequence specifically bind DNA, and can function both as classical transcription factors and as architectural components of chromatin (Kiefer et al. 2007, Lefebvre et al. 2007). We have been modeling SOX gene function using the Drosophila SOX gene Dichaete (D). D has similar biochemical properties to mammalian SOX proteins, and is essential for embryonic segmentation and cell fate specification (Ma et al. 1998, Russell et al. 1996). In this thesis I detail novel functions of D in oogenesis and adult olfactory system development. Chapter two details D expression and function during oogenesis in Drosophila. We show that D is transiently expressed in the oocyte cytoplasm from region 2 of the germarium through stage 8. We demonstrate that D protein can bind gürken mRNA, which was mislocalised in D mutant egg chambers. These studies contribute to our understanding of the establishment of dorsal/ventral polarity and significantly detail a cytoplasmic role for SOX proteins in binding mRNA (Mukherjee et al., 2006). Chapter three details the expression and function of D in the adult Drosophila nervous system. I show that D is prominently expressed in a mixture of excitatory and inhibitory local neurons (LNs) and central complex ring neurons. Hypomorphic D alleles were generated, and the mutant brains exhibited misplacement and mistargeting of specific olfactory projection neurons. These data greatly enhance our understanding of the development of neuronal connectivity in a discrete neural map represented by the fly antennal lobe, and represent a detailed report of SOX gene expression in the adult brain

Staying awake to stay alive: A circuit controlling starvation-induced waking.

The balance of sleep and wake is plastic and changes to meet environmental demands. Mechanisms that allow an animal to suppress sleep and maintain waking in potentially adverse situations could serve adaptive functions in evolution. The fruit fly, Drosophila melanogaster, is well poised as a system in which to explore these questions. The environment changes sleep and wake in flies, e.g., starvation induces waking in Drosophila as it does in many animals. Further, the sophisticated neurobiological toolkit available to Drosophila researchers gives the fly a great advantage as a system to investigate the precise neurobiological mechanisms underlying these adaptive changes. In a paper in this issue of PLOS Biology, Yurgel and colleagues elegantly exploit the advantages of the Drosophila model to map starvation-induced wakefulness to a single pair of peptidergic neurons and their partners

Learning and memory: do bees dream?

In mammals, evidence for memory reactivation during sleep highlighted the important role that sleep plays in memory consolidation. A new study reports that memory reactivation is evolutionarily conserved and can also be found in the honeybee