NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala

We examined the contribution of N -methyl-D-aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single-unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist ±-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single-unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single-unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long-term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning-related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71768/1/j.1460-9568.2004.03513.x.pd