Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in taste processing, is involved in representing anticipatory cues. Although IC responses to anticipatory cues are well established, the role of IC cue-related activity in mediating feeding behaviors is poorly understood. Here, we examined the involvement of the IC in the expression of cue-triggered food approach in mice trained with a Pavlovian conditioning paradigm. We observed a significant change in neuronal firing during presentation of the cue. Pharmacological silencing of the IC inhibited food port approach. Such a behavior could be recapitulated by temporally selective inactivation during the cue. These findings represent the first evidence, to our knowledge, that cue-evoked neuronal activity in the mouse IC modulates behavioral output, and demonstrate a causal link between cue responses and feeding behaviors.insular cortex | reward | anticipation | cue | learning I n natural environments, animals use sensory information from various sources to predict the availability of food (1-3). Repeated pairings of a neutral stimulus with the availability of food leads to the formation of associations. Upon association, foodpredicting cues become capable of triggering the expectation of food. These expectations drive motivation for food seeking and food consumption (4-6). It is generally believed that cues drive behavior by activating reward-related circuits responsible for coordinating food seeking and food consumption. A large body of evidence shows that regions like the amygdala, ventral striatum, orbitofrontal and prefrontal cortices, and ventral tegmental area can be activated by anticipatory cues (7-12). Although the reward circuitry involved in cue-triggered, food-related behaviors has been extensively studied, relatively little attention has been devoted to the role of sensory cortical areas in this process. The insular cortex (IC), for instance, has traditionally been studied for its role in the consummatory and postconsummatory phases of feeding (13)(14)(15)(16)(17). Neuronal ensembles in the IC are involved in taste processing and learning (18-21), and IC function is believed to be limited to the evaluative and sensory aspects of food consumption (22,23). More recent evidence, however, has suggested that the IC can also be involved in processing cues associated with food availability or delivery of addictive drugs (24-28). The presence of neurons that encode for both anticipatory cues and taste suggests a functional integration of reward and expectation processing. The prediction emerging from these studies is that manipulations of IC anticipatory activity might have an impact on food-directed and, in general, reward-directed behaviors. Although pharmacological manipul...