Impact of Temporal Uncertainty on Sign-tracking Behavior

Sign-tracking behavior, also known as “autoshaping”, is defined as approach and interaction with reward-predictive cues. It is associated with addiction-related phenotypes and compulsive behavior. Several previous studies have demonstrated that when there is uncertainty about reward properties (e.g. probability, size), sign-tracking is increased. However, the effect of cue-uncertainty on sign-tracking behavior is not known. Here, using a Pavlovian conditioning paradigm, we manipulated the temporal uncertainty about the appearance of cues by implementing either fixed or variable inter-trial intervals (ITIs) of different durations across groups of mice. We found that temporal uncertainty during acquisition significantly enhances sign-tracking, which persists during extinction, even when ITI variability was different in the extinction session than in the acquisition session. This suggests that the effects of temporal uncertainty are learned and retained, rather than performance-based. Our results demonstrate that sign-tracking behavior is not only modified by the characteristic of the reward, but it can also be modified by the uncertainty regarding cues. These findings highlight how temporal predictability shapes cue-directed behaviors and has implications for understanding reward-related behavioral responses including sign-tracking behaviors.