PREDICTION ERROR ENGAGES NMDA RECEPTORS IN THE BASOLATERAL AMYGDALA COMPLEX FOR PAVLOVIAN FEAR CONDITIONING

The activaiton of N-methyl-D-aspartate receptors (NMDARs) in the basolateral amygdala complex (BLA is thought to be critical for the acquisition of Pavlovian conditioned fear when a conditioned stimulus (CS; e.g., visual or auditory) is paired with an aversive unconditioned stimulus (US; e.g., foot-shock). However, recent studies show that this is not the case and suggest that NMDAR-activation may only be required for Pavlovian fear conditioning when the US is unpredictable. The present study tested this hypothesis using male and female rats. In each experiment, rats received a BLA infusion of the NMDAR antagonist, DAP5, immediately prior to a session in which a novel stimulus, S2 (a sound), was presented in sequence with another stimulus, S1 (a light) and foot-shock (i.e., S2-S1-shock). In a prior stage of the experiment (48 h earlier), the S1 had been consistently paired with the US, inconsistently paired with the US, or consistently presented in the absence of the US. Importantly, the final drug-free testing revealed that the effect of the DAP5 infusion on conditioning to S2 varied with the reinforcement history of S1. Relative to vehicle-injected controls, the DAP5 infusion disrupted conditioning to S2 when the US was not perfectly predicted by S1; and had no effect on conditioning to S2 when the US was perfectly predicted by S1. Hence, within the BLA, the involvement of NMDARs in Pavlovian fear conditioning is indeed determined by the predictability of the US. These results are discussed in relation to contemporary theories of learning, memory and amygdala function.