Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits

Abstract

Delaney AJ, Sedlak PL, Autuori E, Power JM, Sah P. Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits.

Observation of Distressed Conspecific as a Model of Emotional Trauma Generates Silent Synapses in the Prefrontal-Amygdala Pathway and Enhances Fear Learning, but Ketamine Abolishes those Effects

“…On the other hand, the slower decay of NMDAR current suggests increased proportion of NR2B subunits (Monyer et al, 1994;Yuan et al, 2009), which is an indication of postsynaptic changes in NMDA receptor. However, we did not detect differences in sensitivity of NMDAR currents to the NR2B receptor antagonist ifenprodil, which was consistent with a report that all NMDARs in BLA contain at least one NR2B subunit and are sensitive to the antagonist (Delaney et al, 2012).…”

Molecular Mechanisms of Threat Learning in the Lateral Nucleus of the Amygdala

“…158 However, a recent study in BLA slices shows that RNA-interference (RNAi)-mediated knockdown of the GluN2B subunit has little effect on the kinetics of NMDAR activation and conductance but disrupts its association with signaling molecules that are essential for synaptic plasticity. 56 Notably, this is the first study to show that NMDARs exist as triheteromeric complexes of GluN1/GluN2A/GluN2B (as opposed to GluN1/GluN2A or GluN1/ GluN2B diheteromers) in BLA. GluN2B subunits can also be regulated by posttranslational modification, that is, phosphorylation of C-terminal residues that can alter NMDAR localization and coupling to signaling molecules.…”

“…For example, LA infusion of the GluN2B-containing receptor blocker ifenprodil impairs the acquisition of threat memories while leaving normal synaptic transmission and expression of threat memories intact. [54][55][56] However, a recent study suggests that the involvement of GluN2B depends on the strength of conditioning (number of CS-US pairing trials), whereas the less well-studied GluN2A is necessary for all conditioning protocols tested. 57 The role of specific NMDAR subunits in threat learning and their regulation by second messenger signaling and proteinprotein interactions will be discussed in detail below.…”

“…56,[157][158][159] GluN2B (NR2B)-containing receptors have been particularly well studied in amygdala. Rodrigues et al showed that in contrast to broad-spectrum NMDAR antagonist, blockade of GluN2B-containing NMDARs in LA reduces acquisition but not expression of threat memories 54 and does not affect normal synaptic transmission, 54,55 whereas forebrain overexpression of GluN2B subunits enhances threat conditioning.…”

Alteration of the Centromedial Amygdala Glutamatergic Synapses by the BDNF Val66Met Polymorphism

“…The modulation of NMDA receptor subunit composition caused by changes in the GluN2B subunit could be tested using a highly selective GluN2B antagonist ifenprodil (Delaney et al, 2013;Galvin and Ninan, 2014;Williams, 1993). Therefore, to test whether the lack of GluN2B-mediated NMDA receptor transmission accounts for the reduced NMDA current decay time in the BDNF Met/Met group, we compared NMDA EPSC decay time and amplitude in BDNF Met/Met and BDNF Val/Val groups before and after perfusion with ifenprodil (5 and 10 μM, 15 min).…”