Identification of a dopamine pathway that regulates sleep and arousal in Drosophila

Nat Neurosci. 2012 Nov;15(11):1516-23. doi: 10.1038/nn.3238. Epub 2012 Oct 14.

Abstract

Sleep is required to maintain physiological functions, including memory, and is regulated by monoamines across species. Enhancement of dopamine signals by a mutation in the dopamine transporter (DAT) decreases sleep, but the underlying dopamine circuit responsible for this remains unknown. We found that the D1 dopamine receptor (DA1) in the dorsal fan-shaped body (dFSB) mediates the arousal effect of dopamine in Drosophila. The short sleep phenotype of the DAT mutant was completely rescued by an additional mutation in the DA1 (also known as DopR) gene, but expression of wild-type DA1 in the dFSB restored the short sleep phenotype. We found anatomical and physiological connections between dopamine neurons and the dFSB neuron. Finally, we used mosaic analysis with a repressive marker and found that a single dopamine neuron projecting to the FSB activated arousal. These results suggest that a local dopamine pathway regulates sleep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Arousal / physiology*
  • Cyclic AMP / pharmacology
  • Dopamine / genetics
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Dopaminergic Neurons / drug effects
  • Dose-Response Relationship, Drug
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Green Fluorescent Proteins / genetics
  • Luminescent Proteins / genetics
  • Membrane Proteins / metabolism
  • Memory / drug effects
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Mutation / genetics
  • Nerve Net / physiology
  • Neurons / physiology
  • Odorants
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sleep / physiology*
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology
  • Time Factors
  • Transcription Factors / metabolism

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Drosophila Proteins
  • GAL4 protein, Drosophila
  • Luminescent Proteins
  • Membrane Proteins
  • Receptors, Dopamine D1
  • Sodium Channel Blockers
  • Transcription Factors
  • Trp1 protein, Drosophila
  • Green Fluorescent Proteins
  • Tetrodotoxin
  • Cyclic AMP
  • Dopamine