Role of Drosophila circadian circuitry in experience-dependent sleep

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DESCRIPTION (provided by applicant): Sleep has been shown to play an important role in the consolidation of memories in humans, rats and flies (Stickgold et-al, 2000, Ganguly-Fitzgerald et al, 2006). Recent studies have shown that, in addition to playing a strong role in sleep regulation, the circadian clock also influences processes associatedwith learning and;memory (Keisler et al, 2007, Decker et al, 2007). Thus, the neuronal circuits that control circadian rhythms are uniquely positioned to play an important role in coordinating interactions between sleep and memory. We have previously shown that wild-type Drosophila exhibit increased sleep after being housed for several days in a socially-enriched environment and that sleep is also increased following training in a courtship conditioning assay that results in the formation of long-term memories (Ganguly- Fitzgerald et al, 2006). This increase in sleep is dependent on canonical learning and memory genes such as the adenylyl cyclase rutabaga and is largest during the initial hours after lights-on suggesting the involvement of the circadian clock. Although I have also found that mutations in two genes that are involved in regulating synaptic plasticity, the dDA1 dopamine receptor and the blistered transcription factor. Both of these genes are endogenously expressed in circadian pacemaker cells. Thus, the proposed experiments will test the hypothesis that circadian clock circuits regulate increased sleep following social enrichment and that this regulation requires the expression of genes known to be involved in memory formation. First, I will test whether expression of the dopamine receptor dDA1 in circadian circuitry is involved in regulation of experience-dependent sleep. Second, I will examine whether expression of the Drosophila homolog to the mammalian Serum Response Factor, blistered, in circadian pacemaker cells is involved in controlling experience-dependent sleep. Finally, I will test the hypothesis that blistered is required for experience- dependent increase of synaptic terminal number in circadian clock cells. Research Relevance: Sleep is necessary for consolidation of newly formed memories into longer lasting associations in humans and in fruit flies. Given the similarities between sleep in humans and in flies and the genetic tools that are available to study the fruit fly, I propose to use the fruit fly as a model system to identify a brain circuit that is involved in regulating sleep after novel social experiences. I hypothesize that cells that have been previously identified as circadian oscillators are involved in the control of experience-dependent sleep.