Sleep is one of the great biological mysteries. Each night we disconnect ourselves from the world for seven or eight hours—a state that leaves us vulnerable and unproductive. But despite these risks and costs, we still don't know what sleep is good for. This project intends to fill this gap.
Solving the mystery of sleep is important not only for academic reasons. Sleep disturbances are among the most common medical problems, with an estimated occurrence of 10–15% in the general and 30–60% in the older population. They accompany many medical, psychiatric, and neurological conditions and are the leading cause of traffic accidents.
Despite the prevalance of sleep disorders and the proven benefit of treating them for improving the many conditions with which they are associated, therapeutic options remain limited. They include behavioral interventions to improve sleep hygiene and the use of drugs, such as modulators of GABA receptors. These medications are associated with a wide range of side effects, such as morning sedation, rebound insomnia, anterograde amnesia, confusion and injury, and addiction.
The development of new therapeutic concepts requires a deeper understanding of the neuronal control of sleep. We approach this problem by studying the response of fruit flies to sleep loss. Our work showed that, when flies need sleep, a small group of neurons in their brains increase their electrical output, just like a thermostat switches on the furnace when the temperature is too cold. Integral to the sleep switch is the flow of electrical current through two ion channels, called Shaker and Sandman. During sleep, virtually all current goes through Shaker; during waking, a significant portion is shunted through Sandman. The seemingly intractable question "Why do we sleep?" thus becomes a concrete, solvable problem: What molecules or processes determine how much current flows through each of these ion channels? The answers will point to the molecular events preceding the onset of sleep and therefore, by logical necessity, reveal something fundamental about its purpose.
