Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila

In Drosophila, the amidated neuropeptide pigment dispersing factor (PDF) is expressed by the ventral subset of lateral pacemaker neurons and is requir ed for circadian locomotor rhythms. Residual rhythmicity in pdf mutants lik ely reflects the activity of other neurotransmitters. We asked whether othe r neuropeptides contribute to such auxiliary mechanisms. We used the gal4/U AS system to create mosaics for the neuropeptide amidating enzyme PHM; amid ation is a highly specific and widespread modification of secretory peptide s in Drosophila. Three different gal4 drivers restricted PHM expression to different numbers of peptidergic neurons. These mosaics displayed aberrant locomotor rhythms to degrees that paralleled the apparent complexity of the spatial patterns. Certain PHM mosaics were less rhythmic than pdf mutants and as severe as per mutants. Additional gal4 elements were added to the we akly rhythmic PHM mosaics. Although adding pdf-gal4 provided only partial i mprovement, adding the widely expressed tim-gal4 largely restored rhythmici ty. These results indicate that, in Drosophila, peptide amidation is requir ed for neuropeptide regulation of behavior. They also support the hypothesi s that multiple amidated neuropeptides, acting upstream, downstream, or in parallel to PDF, help organize daily locomotor rhythms.