title: A subset of cholinergic mushroom body neurons requires Go signaling to regulate sleep in Drosophila.
abstract: OBJECTIVE
  Identifying the neurochemistry and neural circuitry of sleep regulation is critical for understanding sleep and various sleep disorders. Fruit flies display sleep-like behavior, sharing essential features with sleep of vertebrate. In the fruit fly's central brain, the mushroom body (MB) has been highlighted as a sleep center; however, its neurochemical nature remains unclear, and whether it promotes sleep or wake is still a topic of controversy.
  
  
  METHODS
  We used a video recording system to accurately monitor the locomotor activity and sleep status. Gene expression was temporally and regionally manipulated by heat induction and the Gal4/UAS system.
  
  
  RESULTS
  We found that expressing pertussis toxin (PTX) in the MB by c309-Gal4 to block Go activity led to unique sleep defects as dramatic sleep increase in daytime and fragmented sleep in nighttime. We narrowed down the c309-Gal4 expressing brain regions to the MB α/β core neurons that are responsible for the Go-mediated sleep effects. Using genetic tools of neurotransmitter-specific Gal80 and RNA interference approach to suppress acetylcholine signal, we demonstrated that these MB α/β core neurons were cholinergic and sleep-promoting neurons, supporting that Go mediates an inhibitory signal. Interestingly, we found that adjacent MB α/β neurons were also cholinergic but wake-promoting neurons, in which Go signal was also required.
  
  
  CONCLUSIONS
  Our findings in fruit flies characterized a group of sleep-promoting neurons surrounded by a group of wake-promoting neurons. The two groups of neurons are both cholinergic and use Go inhibitory signal to regulate sleep.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China ; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yinjun
authors.initials: Y
authors.lastname: Tian
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Aike
authors.initials: A
authors.lastname: Guo
mesh_terms: D000818:Animals; D059329:Cholinergic Neurons / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D004331:Drosophila melanogaster / Q000502:physiology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D006801:Humans; D024521:Mushroom Bodies / Q000502:physiology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D012890:Sleep / Q000502:physiology*
chemical_list: D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: Go signaling; Mushroom body; cholinergic neurons; sleep