AbstractThe ability to identify and respond to food is essential for survival, yet little is known about the neural substrates that regulate natural variation in food‐related traits. The foraging (for) gene in Drosophila melanogaster encodes a cGMP‐dependent protein kinase (PKG) and has been shown to function in food‐related traits. To investigate the tissue distribution of FOR protein, we generated an antibody against a common region of the FOR isoforms. In the adult brain we localized FOR to neuronal clusters and projections including neurons that project to the central complex, a cluster within the dorsoposterior region of the brain hemispheres, a separate cluster medial to optic lobes and lateral to brain hemispheres, a broadly distributed frontal‐brain cluster, axon bundles of the antennal nerve and of certain subesophageal‐ganglion nerves, and the medulla optic lobe. These newly described tissue distribution patterns of FOR protein provide candidate neural clusters and brain regions for investigation of neural networks that govern foraging‐related traits. To determine whether FOR has a behavioral function in neurons we expressed UAS‐for in neurons using an elav‐gal4 driver and measured the effect on adult sucrose responsiveness (SR), known to be higher in rovers than sitters, the two natural variants of foraging. We found that pan‐neuronal expression of for caused an increase in the SR of sitters, demonstrating a neural function for PKG in this food‐related behavior. J. Comp. Neurol. 504:570–582, 2007. © 2007 Wiley‐Liss, Inc.