Circadian clocks provide timing signals to organize many developmental and behavioral functions. We have studied the circadian control of daily locomotor rhythms. At 25 o C, adult Drosophila exhibit a rhythmic pattern of locomotion that is maintained under constant conditions. Several gene mutations have been identified which alter or greatly diminish such rhythms, without reducing the amount of locomotion. Many represent genes involved in the basic clock mechanism, including the genes period, timeless, Clock and cycle. There are ~16 identified brain neurons that house the clock mechanism and that provide timing signals for locomotory behavior. We have used genetics to identify the principal neurotransmitter used by these clock neurons as PDF (pigment-dispersing factor, which is encoded by the pdf neuropeptide precursor gene. Under cycling conditions, pdf mutant animals exhibit normal rhythmic behavior; under constant conditions, most become arrhythmic within a few cycles. A minority of pdf mutant animals remain weakly rhythmic. PDF neurons remain differentiated in the absence of their transmitter. The wild type pdf gene largely rescues the mutant behavioral phenotype. Following specific ablation of PDF neurons, we see the same behavioral phenotypes. Therefore, pdf is required for normal organization of circadian locomotory behavior and it encodes the principal transmitter that is released by pacemaker neurons to do so. These results also support the hypothesis that while the PDF neurons are the principal pacemaker neurons for locomotor control, other (non-PDF) pacemaker neurons also contribute. We will present evidence to define the site of chronobiological activity within the preproPDF precursor, and to ask whether the circadian clock is still cycling normally in the pdf mutant background.

Index: circadian clock, neuropeptide, behavior, genetics, PDF

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