Widespread Receptivity to Neuropeptide PDF throughout the Neuronal Circadian Clock Network of Drosophila Revealed by Real-Time Cyclic AMP Imaging

Orie T. Shafer, Dong Jo Kim, Richard Dunbar-Yaffe, Viacheslav O. Nikolaev, Martin J. Lohse, Paul H. Taghert

Research output: Contribution to journalArticlepeer-review

225 Scopus citations

Abstract

The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of ∼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 ∼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.

Original languageEnglish
Pages (from-to)223-237
Number of pages15
JournalNeuron
Volume58
Issue number2
DOIs
StatePublished - Apr 24 2008

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

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