Formation and Retrieval of Inhibitory Avoidance Memory: Differential Roles of Glutamate Receptors in the Amygdala and Medial Prefrontal Cortex

This study investigated the roles of NMDA and AMPA receptors in the amygdala and medial prefrontal cortex in formation and retrieval of affective memory. In a one-trial step-through inhibitory avoidance task, groups of rats with cannulae implanted into these two regions received infusion of 2.5 μg APV or 0.3 μg CNQX 5 min before training, shortly after training or 5 min prior to the 1-day or 21-day retention test. Results showed that pre- or posttraining intra-amygdala infusion of APV or CNQX induced a persistent retention deficit with the pretraining treatment causing a greater effect. Pre- or posttraining infusion of CNQX into the medial prefrontal cortex also induced a persistent retention deficit with the posttraining treatment causing a greater effect. Pre- or posttraining infusion of APV into the medial prefrontal cortex impaired 21-day retention but not 1-day retention. Pretraining infusion of lidocaine into either structure caused a retention deficit, which was not attenuated by activating the other structure with glutamate. Pretest intra-amygdala infusion of CNQX impaired memory expression in the 1-day test, while infusion of CNQX into the medial prefrontal cortex impaired memory expression in the 21-day test. Pretest APV infusion into either structure had no effect on memory expression. These findings suggest that the amygdala and medial prefrontal cortex may be contained in a circuitry responsible for formation of affective memory. The consolidation process involves the NMDA and AMPA receptors in both structures. Further, retrieval of recent affective memory engages amygdala AMPA receptors, whereas retrieval of remote affective memory engages AMPA receptors in the medial prefrontal cortex.