Figure 9.
Model summarizing the findings reported and the hypotheses raised by this work. Ih channel (in green) responds to membrane hyperpolarization and is modulated by cyclic nucleotides, serving as coincidence detector for electrical and chemical signals mediated by ligands that activate G-protein-coupled receptors (such as PDF, dopamine, or other neuropeptides, symbolized by “modulator,” in blue). Ih function is necessary to allow LNvs to fire action potentials in a high-frequency bursting mode, which permits the release of PDF (in orange) at high levels and in a timely manner (top neuron). In the absence or on Ih knock-down (bottom neuron), bursting does not reach such high frequency, and PDF levels at the axonal projections are reduced. Associated to the decreased bursting frequency, large quantities of PDF accumulate at the soma, likely because of a failure in DVCs transport. This may give rise to a hypothetical aberrant PDF release from the overloaded soma, likely overriding the internal temporal control. All in all, these cellular disruptions result in anomalies at the behavioral level, such as disorganization of circadian locomotor activity and an increase in sleep. At the level of the axonal projections, the model represents an early daytime situation, where in control animals PDF levels are high and the axonal terminal are spread out. However, the accumulation and possible aberrant release of PDF from the soma is more likely to happen during the night (Fig. 6).