NMDA receptors in basolateral amygdala principal neurons are triheteromericproteins: physiological role of GluN2B subunits. J Neurophysiol109: 1391'1402, 2013. First published December 5, 2012;doi:10.1152/jn.00176.2012.'N-methyl-D-aspartate (NMDA) receptorsare heteromultimeric ion channels that contain an essential GluN1subunit and two or more GluN2 (GluN2A'GluN2D) subunits. Thebiophysical properties and physiological roles of synaptic NMDAreceptors are dependent on their subunit composition. In the basolateralamygdala (BLA), it has been suggested that the plasticity thatunderlies fear learning requires activation of heterodimeric receptorscomposed of GluN1/GluN2B subunits. In this study, we investigatedthe subunit composition of NMDA receptors present at synapses onprincipal neurons in the BLA. Purification of the synaptic fractionshowed that both GluN2A and GluN2B subunits are present atsynapses, and co-immunoprecipitation revealed the presence of receptorscontaining both GluN2A and GluN2B subunits.The kinetics of NMDA receptor-mediated synaptic currents and pharmacologicalblockade indicate that heterodimeric GluN1/GluN2B receptors areunlikely to be present at glutamatergic synapses on BLA principalneurons. Selective RNA interference-mediated knockdown ofGluN2A subunits converted synaptic receptors to a GluN1/GluN2Bphenotype, whereas knockdown of GluN2B subunits had no effect onthe kinetics of the synaptically evoked NMDA current. Blockade ofGluN1/GluN2B heterodimers with ifenprodil had no effect, butknockdown of GluN2B disrupted the induction of CaMKII-dependentlong-term potentiation at these synapses. These results suggest that, onBLA principal neurons, GluN2B subunits are only present as GluN1/GluN2A/GluN2B heterotrimeric NMDA receptors. The GluN2B subunithas little impact on the kinetics of the receptor, but is essential for therecruitment of signaling molecules essential for synaptic plasticity.