The Drosophila dystonia gene homolog Neurocalcin facilitates sleep by inhibiting a movement-promoting neural network

Primary dystonia is a hyperkinetic movement disorder linked to altered dopaminergic signaling and synaptic plasticity in regions of the brain involved in motor control. Mutations in HPCA, encoding the neuronal calcium sensor Hippocalcin, are associated with primary dystonia, suggesting a function for Hippocalcin in regulating the initiation and/or maintenance of activity. However, such a role for Hippocalcin or Hippocalcin homologs has yet to be demonstrated in vivo. Here we investigate the cellular and organismal functions of the Drosophila Hippocalcin homolog Neurocalcin (NCA), and define a role for NCA in promoting sleep by suppressing nighttime hyperactivity. We show that NCA acts in a common pathway with the D1-type Dop1R1 dopamine receptor and facilitates sleep by inhibiting neurotransmitter release from a multi-component activity-promoting circuit. Our results suggest conserved roles for Hippocalcin homologs in modulating motor control through dopaminergic pathways, suppressing aberrant movements in humans and inappropriate nighttime locomotion in Drosophila.