Background

Overeating and obesity are driven in part by the rewarding properties of food. Interestingly, reward circuits (i.e. dopamine signaling) are potentiated by hunger, thus increasing the reward value of food during times of homeostatic need. This suggests that there is an coordinated regulation of hypothalamic and reward circuits in response to food intake. Here, we investigated how gut signaling influences hypothalamic and reward signaling, and how these circuits interact to promote feeding.

Methods

We used fiber photometry to monitor in vivo calcium dynamics in hypothalamic agouti-related protein (AgRP) neurons and dopamine (DA) signaling in the nucleus accumbens in response to food intake and gastric infusion of nutrients. We next assessed the role of vagal gut-brain signaling on AgRP neuron activity using a complete subdiaphragmatic vagotomy. Finally, to gain insight into the neural pathways that mediate interactions between hypothalamic and reward circuitry, we modulated neural activity in AgRP or DA circuits and measured the effects on food-evoked signaling in the other population.

Results

Food intake rapidly and concomitantly inhibited AgRP neuron activity and potentiated mesoaccumbal DA signaling in food restricted mice. Gastric infusion of nutrients similarly affected activity in these neuron populations, and the effects of gut nutrients and satiation signals on AgRP neurons was attenuated in vagotomized mice. Finally, we provided evidence that the effects of food on AgRP and DA neurons are interdependent, as modulation of either hypothalamic neurons or midbrain dopamine signaling influenced reward-evoked activity changes in the other population.

Conclusions

Our results suggest that (1) gastric nutrients affect hypothalamic and reward circuitry and (2) coordinated activity in AgRP and DA neurons influences activity changes in response to food. Follow-up studies will determine if this relationship between hypothalamic and reward circuitry is dysregulated in obesity and binge eating models.