(A) A schematic diagram depicting anatomical locations for Or42b and Or85a ORNs in the fly antenna as well as their corresponding glomeruli, DM1 and DM5, respectively, in the antennal lobe. LNs release DTK peptide broadly throughout the antennal lobe. (B) A model for how starvation state fine-tunes ORN sensitivity via the actions of neuromodulation of Or42b/DM1 and Or85a/DM5. In the starvation state, sNPF sensitizes the DM1 glomerular responses through additive gain modulation. Tachykinin suppresses DM5 glomerular responses through a divisive gain modulation. (C) The concerted effect of these two neuromodulatory systems increases behavioral attraction and expands the concentration range over which attraction to vinegar manifests. (D) In the DM1 glomerulus, both DTK and sNPF are available and released from the LNs and ORNs, respectively, in both the fed and starved states. DTKR is also present in these terminals in the fed state. Upon starvation, loss of insulin signaling leads to selective upregulation of sNPFR expression in the Or42b ORNs, which leads to their presynaptic facilitation. (E) In the DM5 glomerulus, both DTK and sNPF are available and released from the LNs and ORNs, respectively, in both the fed and starved states. Upon starvation, loss of insulin signaling leads to upregulation of DTKR expression in the Or85a ORNs, leading to their presynaptic inhibition.