These experiments suggest that proboscis extension is triggered by dopamine release from TH-Gal4 neurons acting on D2R, but not DopR. To examine when dopamine is likely
to regulate proboscis extension, we stimulated flies with altered dopaminergic activity with a range of sugar concentrations under different starvation conditions. Flies in which TH-Gal4 neurons were silenced by conditional expression of UAS-Kir2.1 in adults showed decreased probability of extension, as expected (Figures 1C and 3A). As starvation time increased, the response increased, arguing that these flies are still sensitive to other cues related to internal state. However, the response was blunted check details Ion Channel Ligand Library for the highest sugar concentrations, indicating that loss of dopaminergic activity decreases the gain of the response. In the converse experiment, the electrical excitability of dopaminergic neurons was increased by conditional expression of UAS-NaChBac, a low-threshold, slowly inactivating sodium channel. Unlike dTRPA1, this
channel does not drive neural activity by exogenous cues, but instead amplifies the cellular response to membrane depolarization ( Nitabach et al., 2006). Expression of NaChBac in the adult increased the probability of response for all concentrations and starvation conditions ( Figure 3B). Flies with altered dopaminergic activity did not differ in proboscis extension responses to denatonium, a bitter compound, or water, a nonnutritive but acceptable substance (see Figure S1 available online). This result
argues that dopaminergic activity selectively alters the probability of proboscis extension to sucrose, but not to nonnutritious compounds. The probability of proboscis extension depends on sucrose concentration and satiety state. Previous studies have shown that the PR-171 mw activity of gustatory sensory neurons dramatically increases with sucrose concentration (Hiroi et al., 2002 and Marella et al., 2006). The concentration-dependent change in PER probability most likely reflects changes in sensory activity propagating through the circuit. The satiety state also acts to adjust probability of extension, with increased extension to a given concentration occurring when the fly is food deprived. Our behavioral studies argue that the activity of TH-Gal4 neurons serves to adjust the probability of extension to a given sucrose concentration. Thus, dopaminergic neural activity acts as a gain control mechanism to adjust the dynamic range for proboscis extension to sucrose, increasing extension probability when activity is high and decreasing it when it is low.