Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Neurosciences

Language

English (en)

Date of Award

January 2010

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Paul Shaw

Abstract

Although the necessary functions of sleep have not been identified, sleep has been shown to play an important role in the consolidation of memories. Recent studies have shown that, in addition to playing a strong role in sleep regulation, the circadian clock also influences processes associated with learning and memory. Thus, the neural circuits that control circadian rhythms are uniquely positioned to play an important role in coordinating interactions between sleep and memory. Drosophila melanogaster exhibit increased sleep following several days of social experience and require sleep to consolidate long-term memories: LTM) after Courtship Conditioning, an associative memory assay. We have found both that changes in sleep following social experience and that memory consolidation are reliant upon the expression of plasticity-related genes in Pigment Dispersing Factor: PDF)-expressing ventral lateral neurons: LNvs), a core component of the Drosophila circadian clock. Following social enrichment, LNv projections into the medulla exhibit structural plasticity as measured by an increase in the number of synaptic terminals and that downscaling of LNv terminal number after social enrichment requires sleep. We have also found that both LNv structural plasticity and increases in sleep following social enrichment degrade with age. Importantly, restoration of mechanisms that mediate plastic responses in young flies, such as dopaminergic signaling or expression of the transcription factor blistered, restore youthful plasticity to aged flies. These data indicate that Drosophila circadian circuitry influences sleep-wake behavior in an experience-dependent manner and that proper functioning of the LNvs is required for long-term behavioral plasticity. Our observation of sleep-dependent downscaling of LNv terminals following social enrichment also indicates that an important function of sleep is to downscale potentiated synaptic connections. Together, these results establish Drosophila as a robust model system for investigating the genes and neural circuits that mediate the relationship between plasticity and sleep.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7610XB3

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