Phase Coupling of a Circadian Neuropeptide With Rest/Activity Rhythms Detected Using a Membrane-Tethered Spider Toxin:
The regulation of the daily fluctuations that characterize an organism's physiology and behavior requires coordination of the cellular oscillations of individual "clock" neurons within the circadian control network. Clock neurons that secrete a neuropeptide called pigment dispersing factor (PDF) calibrate, or entrain, both the phase of organismal rhythms and the cellular oscillations of other clock neurons. In this study, we tested the hypothesis that phase of PDF secretion rhythms entrains phase of non-PDF neurons and locomotor rhythms using the tethered- toxin technique (which affixes toxins to the cell membrane) to express ion channel-specific peptide toxins in PDF neurons. A particular toxin inhibits inactivation of the Drosophila para sodium (Na+) channel. Inhibition of Na+ channel inactivation in PDF neurons of transgenic flies induces phase advance of PDF rhythm, and correlated phase advance of lights-on anticipatory locomotor activity, suggesting that phase of morning activity is determined by phase of PDF oscillation. Therefore, voltage-gated Na+ channels of Drosophila clock neurons play a key role in determining the phase relationship between circadian transcriptional feedback oscillation and PDF secretion, and PDF-secreting clock neurons entrain the phase of organismal rhythms via the temporal patterning of secreted PDF signals.
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Membrane-tethered toxins to isolate particular neurons of interest...brilliant! I will confess to not being an expert in the field of Drosophila circadian pacemakers, nor am I a neurophysiologist, but I commend these authors on their use of a remarkably novel technique. I could forsee the application of their innovative method to other tissues of interest (including those studied by Dr. Isis). My hat's off to Wu and Nitabach for an elegant piece of work.