RT Journal Article SR Electronic T1 Neurocalcin acts in a clock- and light-modulated dopaminergic pathway to promote night sleep in Drosophila JF bioRxiv FD Cold Spring Harbor Laboratory SP 159772 DO 10.1101/159772 A1 Ko-Fan Chen A1 Angélique Lamaze A1 Patrick Kratschmer A1 James E. C. Jepson YR 2017 UL http://biorxiv.org/content/early/2017/07/05/159772.abstract AB Members of the neuronal calcium sensor (NCS) family act as key regulators of calcium signaling in neurons by modulating target proteins such as voltage- and ligand-gated ion channels in response to changes in intracellular calcium. In Drosophila, the NCS protein Neurocalcin has been shown to be broadly expressed within the nervous system, suggesting important neurobiological roles. However, whether Neurocalcin impacts complex behaviors in Drosophila has remained unclear. Here, using a hypothesis-based guilt-by-association strategy, we identify a novel role for Neurocalcin in promoting night sleep but not day sleep. We show that Neurocalcin acts in a common pathway with the D1-type Dop1R1 dopamine receptor, and that both the circadian clock and light-sensing pathways demarcate the temporal window during which NCA promotes sleep. Furthermore, we find that Neurocalcin functions in a multi-component wake-promoting neural network and demonstrate that the mushroom bodies, a known sleep-regulatory center, are a module within this circuit. Our results define a critical role for Neurocalcin in Drosophila and further our understanding of how distinct sleep periods are genetically regulated.Author summary Sleep in Drosophila occurs during both the day and night, yet the genetic pathways that selectively impact day versus night sleep are poorly understood. Here we uncover a link between the neuronal calcium sensor Neurocalcin and sleep in Drosophila. We show that Neurocalcin acts in a pathway involving the Dop1R1 dopamine receptor to promote sleep during the night, but not the day, and that the night-specific effect of NCA is coordinated by the circadian clock and light-sensing pathways. Furthermore, we identify a complex wake-promoting neuronal network in which NCA functions to regulate sleep, and our results suggest that NCA suppresses output from this circuit. Thus, we identify a novel role for Neurocalcin in Drosophila and shed light on the genetic regulation of distinct sleep stages.