Resources
Authors & Affiliations
Tarun Kamath, Bart Lodder, Eliana Bilsel, Isobel Green, Sara Matias, Paolo Capelli, Michelle Raghubardayal, Jessie Legister, Nikki Tjahjono, Erin Scott, Janet Berrios Wallace, Lin Tian, Naoshige Uchida, Mitsuko Watabe-Uchida, Bernardo Sabatini
Abstract
When animals explore, they choose to learn new information rather than exploit known information. This exploration is modulated by dopamine release in the striatum, a prediction-error teaching signal that allows animals to learn from both rewards and threats depending on the striatal subregion in which dopamine is released. Exploration and dopamine signaling are modulated by internal state, including caloric depletion or “hunger”, such that when animals are hungry they explore their environment more, presumably in an attempt to find food. While this adaptation has been known for decades, the neural circuitry underlying the adaptation is unknown. Moreover, while hunger changes dopamine signaling, this has primarily been studied in the context of food reward, such that hunger increases dopamine signaling which reflects a reward prediction error to increase the animal’s ability to learn environmental cues which predict food reward. We show that hunger restructures an animal’s exploration of behavioral space and increases its directed exploration of a novel, non-obviously calorically rewarding object. We further show that this increased novel object exploration behavior in hunger is driven by decreased phasic dopamine signaling at the tail of the striatum, a dopamine signal that represents a threat prediction error. This dopamine signal is modulated by hunger through the activity of agouti-related peptide (AgRP) neurons, putative “hunger neurons” in the arcuate nucleus of the hypothalamus (ARC). We thus delineate a neural circuit that translates internal state to modify the ability of an animal to learn to avoid threats, a presumably evolutionarily adaptive behavior that allows hungry animals to explore more in the face of potential threats to find food