The Emerging Involvement of Glia in Sleep: Insights from Drosophila melanogaster

Abstract

Sleep is a pervasive, but enigmatic behavioral state, and the search for its cellular and molecular correlates and purpose has encompassed the entire brain. Glia are important constituents of the nervous system, intricately tied to neuronal activity, and serving many functions which coincide with the predominant hypotheses of sleeps functions. Nevertheless, the contributions of these populations to sleep have so far been understudied. In Chapter 1, the basics of sleep as a phenomenon are introduced, and are followed by a discussion of the potential functions this state fulfills. Sleep is regulated by distinct neuronal populations, which are described, with particular emphasis on Drosophila melanogaster circuitry. This serves as context for reviewing the nascent literature on glial roles in sleep function and regulation. The work of this thesis investigates new contributions to this interaction, using the fly as a model system. Chapter 2 presents findings which implicate endocytic trafficking in the barrier glia, the fly equivalent of a blood-brain barrier, as both an influence on sleep amount, and a functional correlate of the state. An additional mechanism to astrocytic regulation of sleep is introduced in Chapter 3, by describing a monoamine catabolizing enzyme which is expressed in astrocytes, and is involved in homeostatic sleep control in the fly. Chapter 4 returns to the barrier glia, and provides preliminary findings from metabolomic profiling and a behavioral screen seeking to understand which barrier-enriched genes may be consequential for sleep. Together these results expand the scope of glial involvement in sleep and Chapter 5 concludes with a discussion of the broader implications of barrier functions in sleep