FUNCTIONAL ANALYSIS OF SLEEP HOMEOSTASIS IN DROSOPHILA

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Although the precise function of sleep remains unknown, there is little question that sleep is required for maintaining optimal performance in a large and diverse number of biological systems. Indeed, cognitive impairments associated with aging and neurodegenerative disorders are frequently accompanied by deficits in sleep physiology and architecture. We have previously shown that enhanced sleep can reverse memory deficits even in flies with catastrophic lesions to their primary memory center. We have now mapped a minimal circuitry required by this memory assay. Using genomics and behavioral genetics we have identified genes that can restore memory when they are modulated in a single circuit-component in a similar fashion as that produced by sleep. In this proposal we will determine the molecular pathways that regulate these genes. In addition, we will use calcium imaging to determine how restoring a single circuit component modulates the activity of other circuit components to restore memory during brain damage or the expression of Human Alzheimer's' related genes.