Temporal prediction error triggers amygdala-dependent memory updating in appetitive operant conditioning in rats.

Reinforcement learning theories postulate that prediction error, i.e., a discrepancy between the actual and expected outcomes, drives reconsolidation and new learning, inducing an updating of the initial memory. Pavlovian studies have shown that prediction error detection is a fundamental mechanism in triggering amygdala-dependent memory updating, where the temporal relationship between stimuli plays a critical role. However, in contrast to the well-established findings in aversive situations (e.g., fear conditioning), only few studies exist on prediction error in appetitive operant conditioning, and even less with regard to the role of temporal parameters. To explore if temporal prediction error in an appetitive operant paradigm could generate an updating and consequent reconsolidation and/or new learning of temporal association, we ran four experiments in adult male rats. Experiment 1 verified whether an unexpected delay in the time of reward's availability (i.e., a negative temporal prediction error) in a single session produces an updating in long-term memory of temporal expectancy in an appetitive operant conditioning. Experiment 2 showed that negative prediction errors, either due to the temporal change or through reward omission, increased in the basolateral amygdala nucleus (BLA) the activation of a protein that is critical for memory formation. Experiment 3 revealed that the presence of a protein synthesis inhibitor (anisomycin) in the BLA during the session when the reward was delayed (Error session) affected the temporal updating. Finally, Experiment 4 showed that anisomycin, when infused immediately after the Error session, interfered with the long-term memory of the temporal updating. Together, our study demonstrated an involvement of BLA after a change in temporal and reward contingencies, and in the resulting updating in long-term memory in appetitive operant conditioning.