User:CristinTROC/sandbox

The 150 pacemaker neurons in Drosophila are organized into two groups of cells called M (morning) and E (evening) oscillators in the small and large lateral neurons (LNvs). These two groups of cells were first observed by Colin Pittendrigh in 1976. As indicated by their names, the two oscillators control circadian rhythm at different times of the day, yet the two must coordinate to synchronize circadian activity.

PDF synchronizes phase of M oscillators, while in E oscillators PDF decelerates their cycling and supports their amplitude. Stoleru et al. used mosaic transgenic animals with different circadian periods to study the two oscillators. Their study showed that M-cells periodically send a "reset" signal which determines the oscillations of the E-cells. It is believed that the reset signal is PDF, because it is M-cell specific and plays a large role in maintaining normal rhythmicity.

PDF from s-LNv is responsible for the maintenance of a free-running rhythm, while PDF from large lateral ventral neurons is not required for normal behavior. Experiments at Brandeis University have shown that PDF neuropeptide is localized in small lateral ventral neurons (s-LNv) that specifically control morning anticipatory behavior. However, it has been found that large LNv working with other circadian neurons is sufficient to rescue the morning anticipation behavior and startle response in s-LNv-ablated flies. Thus, PDF's role in setting the free-running rhythm and the timing of light dark cycles comes from both types of lateral ventral neurons.

Further evidence of distinct E and M peaks in Drosophila was provided by Grima et al. This work confirmed that the small lateral ventral neurons, which express PDF, are necessary for the morning peak in Drosophila circadian rhythms. Flies lacking functional s-LNv did not possess a lights-on anticipatory activity for the morning peak.

In addition to the LNv, another study has found that a subset of the posterior dorsal neurons 1 (DN1(p)s) modulate the startle response to the onset of light, as flies with mutated ion channels in these neurons show reduced anticipatory behavior and free-running rhythms. The deficit can be rescued by synapsing PDF-expressing neurons onto mutated DN1(p)s, as PDF neurons is sufficient to induce high level of Timeless (gene) protein, an essential protein that regulates circadian rhythm.

Other behavioral aspects of Drosophila such as eclosion activity have been monitored with ectopic expression of pdf, which in this case is concentrated in the dorsal central brain. These alterations in expression caused severely altered rhythmic behavior in eclosion of larvae, further substantiating the evidence that PDF modulates the rhythmic control of Drosophila behavior.