The hedonic feeding system comprises the mesolimbic dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), where a population of D1R-expressing medium spiny neurons (D1R-MSNs) project to the lateral hypothalamus (LH), from where GABA neurons project on VTA GABA neurons, creating a disinhibitory circuit motive. Activation of this circuit by food can lead to positive reinforcement. The homeostatic system includes the arcuate (Arc) and paraventricular hypothalamus (PVH). The two major types of GABA neurons projecting from ARC to PVH are AgRP and POMC neurons, which are under the control of the hormones leptin, ghrelin, and insulin. PVH neurons express MC4 receptors and project to the parabrachial nucleus (PBN), which controls motor circuits of eating. The activity of AgRP neurons codes for hunger, which triggers food intake and may drive negative reinforcement. Some D1R-MSNs project back to the VTA preferentially connecting to GABA neurons, which relay the information to more dorsally projecting DA neurons. Within a few loops, this reaches the nigrostriatal projection. Orbitofrontal to dorsal projection neurons have been implicated in compulsive reward seeking. Several projections serve as the crosstalk between the homeostatic and the hedonic systems. These include ArgRP neurons projecting to the LH and POMC neurons projecting to the NAc, where they can release endorphins. BLA, basolateral amygdala; Xi, xiphoid body; PVT, paraventricular thalamus; mPFC, medial prefrontal cortex.
