Abstract:

Why and how we sleep has been a matter of speculation and study for millennia. Every day our brains cycle between waking and sleeping states. Both of these brain states are highly active, but the nature of the activity and the connection of the brain to the outside world in each state are distinct. Primate and rodent model systems have provided great insights into sleep, but the circuitry in these organisms is quite complex. The recent finding that insects sleep suggests that Drosophila melanogaster, a simple and genetically tractable organism, can be used to study this process.

In recent years, work from my lab and others has exploited the new genetic and electrophysiological tools available in Drosophila to push forward our understanding of sleep by identification and manipulation of the underlying circuitry. In this talk I will discuss the evolutionary conservation of sleep at the behavioral and circuit levels in the fly and how dissection of the circuitry in this organism may allow us to understand the fundamental nature of sleep regulation.

As in mammals, sleep in flies is regulated by both circadian and homeostatic drives, and the onset of the sleep state correlates with changes in high frequency brain activity and an increase in arousal thresholds for acute sensory stimuli. The circuit that generates this behavior consists of GABAergic sleep-promoting neurons which make contacts with wake promoting neurons that are also part of the circadian clock circuit and receive light input. Other brain areas have been identified that may act to modulate this small core circuit. The ability to acutely and chronically control neuronal activity in specific parts of this circuit will allow a detailed understanding of the fly sleep switch. Pressing questions such as how integration over multiple time scales can occur in the switch can be addressed using these tools and will have implications for studies of mammalian switch function. Identification of new circuit components that feed into the integrator, and the ongoing efforts in gene discovery which are providing new molecules that regulate sleep, will make flies true contributors to our understanding of this human behavior.