Fig. 5.

A model for the hunger regulation of adaptive feeding behaviors in Drosophila larvae. Our results suggest that DILP2 neurons, and possibly together with DILP4 neurons, negatively regulate two downstream hunger-responsive feeding systems: an NPF/NPFR1-dependent pathway specialized for motivated feeding and an NPF/NPFR1-independent pathway for general enhancement of feeding rate. In DILP neurons, dS6K activity is likely to positively regulate DILP synthesis and/or release. In fed larvae, a relatively high level of DILP signaling suppresses the two downstream pathways. In fasted animals, hunger stimuli down-regulate dS6K activity in DILP neurons, which in turn leads to decreased DILP signaling and therefore disinhibition of the two pathways. The former overrides the high threshold set by the default pathway, enabling hungry animals to engage in motivated foraging and food selection. The latter enhances feeding rate, allowing animals to compete effectively for limited food sources. DILPs negatively regulate the NPFR1 pathway through the dInR/dPI3K/dS6K pathway in NPFR1 neurons. Our data also implicate the presence of a separate default pathway for ad libitum feeding of higher-quality foods (baseline feeding) by fed larvae. This default pathway may be largely insensitive to DILP or NPF signaling, because overexpression of dS6K, DILPs, or NPFR1 in fed larvae did not affect baseline feeding in the presence of the liquid food (see Figs. 1, 2, 3 and data not shown).