Both NR2A and NR2B subunits of the NMDA receptor are critical for long-term potentiation and long-term depression in the lateral amygdala of horizontal slices of adult mice.

The lateral nucleus of the amygdala (LA) is implicated in emotional and social behaviors. We recently showed that in horizontal brain slices, activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations in the LA, such as long-term potentiation (LTP) and long-term depression (LTD). In the LA, NR2A- and NR2B-type NMDRs coexist in synapses of LA projection neurons. We assessed the contribution of the two NMDAR subtypes to LA-LTP and LA-LTD in adult mouse brain slices by different induction protocols and by different inputs to LA neurons in the presence of different NMDAR subunit antagonists. In general, our results indicate that both NR2A and NR2B subunits are required for the formation of LA-LTP and LA-LTD. The abolishment or reduction of plasticity changes by these compounds could be due to the reduction in calcium influx via NMDARs. We also show, to our knowledge for the first time, that paired-pulse (40-msec interstimulus interval), low-frequency stimulation of external capsule fibers causes stable LTD. Rather than resulting from exclusive roles of the NMDAR subtypes, the synaptic plasticity response in the amygdala appears to be directed by the pattern of synaptic activation and the used inputs, which recruit the major NMDAR subtypes to variable extents.