A Self-Sustaining, Light-Entrainable Circadian Oscillator in the Drosophila Brain

BACKGROUND The circadian clock of Drosophila is able to drive behavioral rhythms for many weeks in continuous darkness (DD). The endogenous rhythm generator is thought to be generated by interlocked molecular feedback loops involving circadian transcriptional and posttranscriptional regulation of several clock genes, including period. However, all attempts to demonstrate sustained rhythms of clock gene expression in DD have failed, making it difficult to link the molecular clock models with the circadian behavioral rhythms. Here we restricted expression of a novel period-luciferase transgene to certain clock neurons in the Drosophila brain, permitting us to monitor reporter gene activity in these cells in real-time. RESULTS We show that only a subset of the previously described pacemaker neurons is able to sustain PERIOD protein oscillations after 5 days in constant darkness. In addition, we identified a sustained and autonomous molecular oscillator in a group of clock neurons in the dorsal brain with heretofore unknown function. We found that these "dorsal neurons" (DNs) can synchronize behavioral rhythms and that light input into these cells involves the blue-light photoreceptor cryptochrome. CONCLUSIONS Our results suggest that the DNs play a prominent role in controlling locomotor behavior when flies are exposed to natural light-dark cycles. Analysis of similar "stable mosaic" transgenes should help to reveal the function of the other clock neuronal clusters within the fly brain.