Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning

The lateral nucleus of the amygdala (LA) is an essential component of the n eural circuitry underlying Pavlovian fear conditioning. Although blockade o f NMDA receptors in LA and adjacent areas before training disrupts the acqu isition of fear conditioning, blockade before testing also often disrupts t he expression of fear responses. With this pattern of results, it is not po ssible to distinguish a contribution of NMDA receptors to plasticity from a role in synaptic transmission. In past studies, NMDA blockade has been ach ieved using the antagonist D, L-2-amino-5-phosphovalerate, which blocks the entire heteromeric receptor complex. The present experiments examined the effects of selective blockade of the NR2B subunit of the NMDA receptor in L A using the selective antagonist ifenprodil. Systemic injections of ifenpro dil before training led to a dose-dependent impairment in the acquisition o f auditory and contextual fear conditioning, whereas injections before test ing had no effect. Intra-amygdala infusions of ifenprodil mirrored these re sults and, in addition, showed that the effects are attributable to a disru ption of fear learning rather than a disruption of memory consolidation. NM DA receptors in LA are thus involved in fear conditioning, and the NR2B sub unit appears to make unique contributions to the underlying plasticity.