Investigation of a newly identified group of neurons regulating sleep and feeding behaviors. - Project Abstract To ensure survival , animals must satisfy a variety of needs that lead to what are often mutually exclusive motivated behaviors. An example of such a behavior is sleep, a process that has been described in a variety of species ranging from jellyfish to humans. Although the precise function of sleep remains unknown, there is ample evidence supporting the notion that sleep is required for maintaining optimal physiological and behavioral performance. Importantly, sleep is regulated by two processes, the circadian clock which gates the occurrence of sleep, and the sleep homeostat which controls the intensity and duration of sleep. Beyond the clock and the homeostat, a variety of sensory inputs and internal states can modulate sleep in significant ways. For example, animals can dramatically modify, reduce, or completely forego sleep if their internal needs and/or external circumstances demand it. Importantly, sleep competes with other essential motivated behaviors, such as feeding. This implies that the decision to engage in, remain in, or exit sleep behavior must be weighed against the drive to perform other key motivated behaviors. Thus, to maximize survival, organisms must constantly assess their environment and their internal needs and alter their physiology and behaviors accordingly. The mutually exclusive nature of sleep and feeding behaviors implies that each of these individual motivational drives must not only be able to modulate the neuronal circuits underlying their associated behavior but also those of the competing one. Although much is known about neural circuits regulating individual behaviors, interactions between them are less well characterized. Understanding how behavioral decisions are made, and how the neuronal circuits underlying different behaviors interact, is a key aspect of modern neurobiology that will help us understand how the nervous system can help organisms adapt to an ever-changing environment and prioritize behaviors in a way that maximizes survival. We have identified two novel sleep- promoting neurons in the Drosophila central nervous system. Interestingly, these neurons also modulate feeding. In addition, we discovered that the activity of these two neurons is regulated by diet composition. In this proposal, we will use the power of the Drosophila model to investigate how these two neurons modulate sleep and feeding. We will identify the circuits, genes and neuromodulators involved in these relationships. Since the molecular mechanisms that regulate feeding and sleep are evolutionary conserved between Drosophila and mammals, we anticipate that this proposal will uncover regulatory principles that are relevant to human physiology. .
