A hypothalamic circuit links hunger to mesolimbic dopamine to drive feeding
Year: 2026
Type: preprint
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.
Institutions: Monell Chemical Senses Center, Yale University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Leica STELLARIS 5 Confocal Microscope, Uncovering novel roles for dorsal root ganglia neurons in nutrient sensing and food intake control, Harnessing sensory food circuits to influence feeding behavior, Interdisciplinary Training in the Chemical Senses, Unraveling the homeostatic and hedonic circuits underlying feeding behavior and obesity
OpenAlex ID: W7213267684