Components of the mesolimbic DA system are shown superimposed upon an image of GFP-containing LepRb neurons as in Figure 1. At its core, this system contains a set of DA neurons within the VTA and that project to the striatum (including the nucleus accumbens (NAc), amygdala, and PFC) to encode the incentive salience of natural and artificial rewards. Leptin may modify the activity of the mesolimbic DA system in a number of ways, including by the direct regulation of a LepRb-expressing population of VTA DA neruons. Additionally, leptin regulates the lateral hypothalamic area (LHA- a major upstream regulator of the mesolimbic DA system) via a number of mechanisms. In addition to containing a set of LepRb-expressing neurons, the LHA contains OX neurons (pink) that project to and regulate VTA DA neurons and MCH neurons (light blue) that project to the striatum. Putative projections from LepRb-containing neurons are denoted as green arrows.