When faced with starvation, animals become more aware of food-related stimuli, at the expense of other behaviors such as courtship. Underlying this heightened stimulus perception is the altered activity of the sensory systems, particularly the olfactory system. To study this, the model organism Drosophila was used due to its simple anatomical olfactory and neural systems, and its genetic tractability. We used a high-throughput single-fly assay to measure the effect of starvation duration on food search behavior. We found mild and severe starvation conditions recruit differential neural substrates for odor search behavior. A signaling pathway for short Neuropeptide F (sNPF) in the mushroom body, particularly in the γ lobe, is shown to be required for this severe starvation-induced food search behavior, where sNPF receptors are localized on
the γ1 and γ2 MBONs. Lastly, the increased excitability of the γ1 and γ2 mushroom body output neurons (MBONs) was able to induce severe starvation behavior in mildly starved flies reinforcing the state-dependent neural plasticity of Drosophila. These results suggest a sNPF-signaling pathway that modulates the activity of the mushroom body in order to increase the food search behavior of Drosophila as starvation progresses.