Manipulating the revision of reward value during the intertrial interval increases sign tracking and dopamine release

Recent computational models of sign tracking (ST) and goal tracking (GT) have accounted for observations that dopamine (DA) is not necessary for all forms of learning and have provided a set of predictions to further their validity. Among these, a central prediction is that manipulating the intertrial interval (ITI) during autoshaping should change the relative ST-GT proportion as well as DA phasic responses. Here, we tested these predictions and found that lengthening the ITI increased ST, i.e., behavioral engagement with conditioned stimuli (CS) and cue-induced phasic DA release. Importantly, DA release was also present at the time of reward delivery, even after learning, and DA release was correlated with time spent in the food cup during the ITI. During conditioning with shorter ITIs, GT was prominent (i.e., engagement with food cup), and DA release responded to the CS while being absent at the time of reward delivery after learning. Hence, shorter ITIs restored the classical DA reward prediction error (RPE) pattern. These results validate the computational hypotheses, opening new perspectives on the understanding of individual differences in Pavlovian conditioning and DA signaling.Author summary: In classical or Pavlovian conditioning, subjects learn to associate a previously neutral stimulus (called “conditioned” stimulus; for example, a bell) with a biologically potent stimulus (called “unconditioned” stimulus; for example, a food reward). In some animals, the incentive salience of the conditioned stimuli is so strong that the conditioned response is to engage the conditioned stimuli instead of immediately approaching the food cup, where the predicted food will be delivered. These animals are referred to as “sign trackers.” Other animals, referred to as “goal trackers,” proceed directly to the food cup upon presentation of the conditioned stimulus to obtain reward. Understanding the mechanisms by which these divergent behaviors develop under identical environmental conditions will provide powerful insight into the neurobiological substrates underlying learning. Here, we test predictions made by a recent computational model that accounts for a large set of studies examining goal-/sign-tracking behavior and the role that dopamine plays in learning. We show that increasing the duration of the time between trials leads more to the development of a sign-tracking response and to the release of dopamine in the nucleus accumbens. During conditioning with shorter intertrial intervals, goal tracking was more prominent, and dopamine was released upon presentation of the conditioned stimulus but not during the time of reward delivery after training. Thus, shorter intertrial intervals restored the classical dopamine reward prediction error pattern. Our results validate the computational hypothesis and open the door for understanding individual differences to classical conditioning.