Widespread receptivity to neuropeptide PDF throughout the neuronal
circadian clock network of Drosophila revealed by real-time cyclic
AMP imaging
Neuron, 58 (2):
223-37 (April 2008)Shafer, Orie T Kim, Dong Jo Dunbar-Yaffe, Richard Nikolaev, Viacheslav
O Lohse, Martin J Taghert, Paul H 2F32NS053222-02/NS/NINDS NIH HHS/United
States MH067122/MH/NIMH NIH HHS/United States NS057105/NS/NINDS NIH
HHS/United States NS21749/NS/NINDS NIH HHS/United States P30 NS057105-039005/NS/NINDS
NIH HHS/United States R01 MH067122-04/MH/NIMH NIH HHS/United States
R01 MH067122-05/MH/NIMH NIH HHS/United States R01 NS021749-21/NS/NINDS
NIH HHS/United States Research Support, N.I.H., Extramural United
States Neuron Neuron. 2008 Apr 24;58(2):223-37..Abstract
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.