Kamath, T.; Lodder, B.; Bilsel, E.; Green, I.; Dalangin, R.; Capelli, P.; Raghubardayal, M.; Legister, J.; Hulshof, L. G.; Wallace, J. B.; Tian, L.; Uchida, N.; Watabe-Uchida, M.; Sabatini, B. L.

Caloric depletion leads to behavioral changes that help an animal find food and restore its homeostatic balance. Hunger increases exploration and risk-taking behavior, allowing an animal to forage for food despite risks; however, the neural circuitry underlying this change is unknown. Here, we characterize how hunger restructures an animal\'s spontaneous behavior as well as its directed exploration of a novel object. We show that hunger-induced changes in exploration are accompanied by and result from modulation of dopamine signaling in the tail of the striatum (TOS). Dopamine signaling in the TOS is modulated by internal hunger state through the activity of agouti-related peptide (AgRP) neurons, putative \"hunger neurons\" in the arcuate nucleus of the hypothalamus. These AgRP neurons are poly-synaptically connected to TOS-projecting dopaminergic neurons through the lateral hypothalamus, the central amygdala, and the periaqueductal grey. We thus delineate a hypothalamic-midbrain circuit that coordinates changes in exploration behavior in the hungry state.