Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging

Neuron. 2008 Apr 24;58(2):223-37. doi: 10.1016/j.neuron.2008.02.018.


The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal
  • Brain / cytology
  • Circadian Rhythm / physiology*
  • Colforsin / pharmacology
  • Computer Systems
  • Cyclic AMP / metabolism*
  • Diagnostic Imaging
  • Dose-Response Relationship, Drug
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Insect Hormones / genetics
  • Insect Hormones / metabolism
  • Luminescent Proteins / metabolism
  • Motor Activity / genetics
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropeptides / metabolism*
  • Neuropeptides / pharmacology


  • Dh31 protein, Drosophila
  • Drosophila Proteins
  • Insect Hormones
  • Luminescent Proteins
  • Neuropeptides
  • pdf protein, Drosophila
  • Colforsin
  • Cyclic AMP