Appetite to learn: An allostatic role for AgRP neurons in the maintenance of energy balance

The relationship between hunger and subsequent feeding has undoubtedly provided strong selective pressures that underpin motivation, learning and memory processes. Together, these behaviours optimise food seeking, food identification, navigation within an environment for food collection, food cultivation and harvest. That hunger affects a broad range of behavioural adaptations suggests that the neural systems sensing and responding to hunger play critical roles in these adaptations. In this review, we examine the role of hunger sensing AgRP neurons in motivation, learning and memory. We discuss how the sensory detection of food or food cues influences AgRP neural activity and how food acts as an important behavioural reinforcer in response to hunger. With this in mind, we reconcile how AgRP neurons transmit a negative valence learning signal when food is not present and how AgRP-driven motivation and learning in the presence of food is positively reinforcing. Finally, we highlight how a homeostatic model of AgRP function does not adequately account for the predictive actions, and adaptive changes, of AgRP neural activity in response to food or learned food cues. We argue that energy allostasis is a more appropriate model, in which AgRP neurons maintain homeostasis by predicting and preparing to meet perceived energy demands through adaptive and learned pre-emptive changes in neural activity. Within this allostatic framework, AgRP-driven changes in motivation, learning and memory are critical for the maintenance of energy balance.