Octopamine (OA), the invertebrate homolog of norepinephrine, has been implicated in multiple behaviors in Drosophila such as feeding, sleep, and aggression. The precise circuit mechanisms by which octopamine regulates these behaviors remains largely unexplored. Using a high resolution neurogenetic screening we have identified a subset of octopamine neurons (VPM 4,5) that suppresses sleep and increases wakefulness. Neuroanatomical analysis reveals that these neurons project to the mushroom body (MB), an associative neural network analogous to the mammalian cortex. Using genetic, anatomical, and behavioral approaches we show that the OA-VPM neurons release octopamine that interacts with subsets of dopamine neurons in the MB in regulating sleep. Furthermore, calcium imaging studies show that flies that are sleep deprived display reduced activity within OA-VPM neurons as compared to sleep-replete controls. Taken together, these results reveal octopamine is important in sleep regulation through these neuronal connections. In addition to presenting this data, we will also discuss potential receptor mediated mechanisms underlying these connections
