Journal
NEURON
Volume 58, Issue 2, Pages 223-237Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2008.02.018
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Funding
- NIMH NIH HHS [R01 MH067122-05, R01 MH067122-04, MH067122, R01 MH067122] Funding Source: Medline
- NINDS NIH HHS [P30 NS057105-039005, F32 NS053222, P30 NS057105, R01 NS021749-21, 2F32NS053222-02, R01 NS021749, NS057105, NS21749] Funding Source: Medline
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The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of similar to 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 similar to 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.
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