(a) Heat map indicating the expression of neurotransmitter related genes in individual AKHR+ and AKHR- neurons. Red and black blocks represent genes that could and could not be detected by RT-PCR, respectively. For a complete list of all 10 genes we examined see Supplementary file 1. (b) Representative RT-PCR bands for indicated genes shown in a. (c) Gene expression in five GFP+ cells assayed by RNA-seq (shown in RPKM). (d–e) Midline crossing activity of indicated genotypes assayed in the presence of 5% sucrose ('+Sucrose') or 2% agar ('-Sucrose') (n = 38–48). (f) Average daily midline crossing activity of indicated genotypes in d–e. (g–h) Average daily midline crossing activity of indicated genotypes (n = 43–65). (i) A working model. Starvation promotes both food seeking and food consumption. Food seeking has two components: food targeting (i.e. perception of food cues) and environmental exploration (i.e. hyperactivity). In this present study (highlighted in red), we have shown that a small group of octopaminergic neurons located in the fly brain are both necessary and sufficient for starvation-induced hyperactivity, an important aspect of food seeking. These neurons express AKHR and dInR, the receptors of AKH and DILPs, respectively. These neurons are octopaminergic (OA), and likely exert their behavioral effect via downstream neurons expressing certain octopamine receptor(s) (OA-R). It is worth noting that the regulation of starvation-induced hyperactivity is independent from that of food consumption, and vice versa. NS, p>0.05; **p<0.01; ***p<0.001.