Gut derived signals modulate neural signaling and behavior, yet how the gut-brain signaling affects the reward system is understudied. The nucleus accumbens (NAc) is the main input structure of the brain’s reward system and is involved in hedonic pathologies such as substance abuse and overeating. Bariatric surgery (BaS), used to treat obesity, increases secretion of gut-derived hormones that signal to hypothalamic POMC+ neurons. These POMC+ neurons project to NAc neurons and activate the melanocortin-4-receptor (MC4R), forming a link between the gut, hypothalamus and the reward system. Indeed, BaS modulates food preference and is associated with a higher risk for alcohol use disorder in patients. We will use mouse BaS to study how gastrointestinal signaling affect the neurophysiology of the NAc. Preliminary data show that BaS modulates the neurophysiology of NAc medium spiny neurons (MSNs) in a cell-type-dependent manner consistent with suppression of hedonic signaling, and alters the response of MSNs to MC4R agonism. We will characterize the effects of BaS on the NAc transcriptome, the physiology of POMC+ neurons projecting to the NAc, and the role of MC4R in mediating the effects of BaS on the NAc, to reveal a gut-brain pathway affecting hedonic signaling and addiction.