A hypothalamic circuit links hunger to mesolimbic dopamine to drive feeding

Abstract

Hunger enhances the motivational value of food, but the neural circuits linking homeostatic hunger neurons to dopamine systems remain poorly understood. Here, we identify a hypothalamic-midbrain neural circuit through which AgRP neurons engage the mesolimbic dopamine system. We demonstrate that AgRP neuron activity is both necessary and sufficient for the potentiated dopamine response to food by hunger, and that they achieve this by reducing inhibitory drive onto midbrain dopamine neurons. Importantly, this AgRP neuron-evoked dopamine signaling is required for subsequent food intake. Mechanistically, we find that AgRP neuron projections to NPY-sensitive paraventricular hypothalamic neurons selectively amplify food-evoked dopamine release to promote feeding behavior. These findings reveal a circuit mechanism through which hunger recruits dopamine signaling to transform physiological need into motivated feeding behavior.