Infusion of the NMDA receptor antagonist, DL-APV, into the basolateral amygdala disrupts learning to fear a novel and a familiar context as well as relearning to fear an extinguished context

Abstract

Ample evidence suggests that activation of NMDA receptors (NMDAr) in the basolateral complex of the amygdala (BLA) is necessary for context fear conditioning. The present series of experiments examined whether this activation was still required when the to-be-shocked context had a history. We found that BLA infusion of the selective NMDAr antagonist DL-APV impaired the acquisition of fear responses to a novel context, a moderately familiar context, or a highly familiar context. The same treatment also impaired the reacquisition of fear responses to a dangerous context, a context extinguished to criterion, or a context massively extinguished. Importantly, DL-APV persistently suppressed fear responses, suggesting that the NMDAr antagonist disrupted basal synaptic transmission in the BLA. Therefore, we conclude that neuronal activity in the BLA is critical for learning and relearning context-conditioned fear. This finding is consistent with current neural models that attribute context fear conditioning to interactions among several brain regions, most notably the hippocampus and the BLA.