The habenula governs the attribution of incentive salience to reward predictive cues.

The attribution of incentive salience to reward associated cues is critical for motivation and the pursuit of rewards. Disruptions in the integrity of the neural systems controlling these processes can lead to avolition and anhedonia, symptoms that cross the diagnostic boundaries of many neuropsychiatric illnesses. Here, we consider whether the habenula (Hb), a region recently demonstrated to encode negatively valenced events, also modulates the attribution of incentive salience to a neutral cue predicting a food reward. The Pavlovian autoshaping paradigm was used in the rat as an investigative tool to dissociate Pavlovian learning processes imparting strictly predictive value from learning that attributes incentive motivational value. Electrolytic lesions of the fasciculus retroflexus (fr), the sole pathway through which descending Hb efferents are conveyed, significantly increased incentive salience as measured by conditioned approaches to a cue light predictive of reward. Conversely, generation of a fictive Hb signal via fr stimulation during CS+ presentation significantly decreased the incentive salience of the predictive cue. Neither manipulation altered the reward predictive value of the cue as measured by conditioned approach to the food. Our results provide new evidence supporting a significant role for the Hb in governing the attribution of incentive motivational salience to reward predictive cues and further imply that pathological changes in Hb activity could contribute to the aberrant pursuit of debilitating goals or avolition and depression-like symptoms.