LTP: GluN2B on the go

Abstract

LTP, the lasting increase in synaptic transmission following heightened activity, is viewed as the physiological basis of learning. In this issue of The EMBO Journal, Dupuis et al find that certain NMDARs diffuse away upon LTP. Antibodies against the NMDAR from patients with autoimmune synaptic encephalitis prevent this redistribution and LTP.

Figure 1. Hypothetical model of allosteric mechanisms upon binding of glutamate to GluN2B and the co-agonist glycine to GluN1

(A) The Ca²⁺ influx triggers autophosphorylation of the dodecameric CaMKII on T286 (center) for the recruitment of CKII to GluN2B, S1480 phosphorylation, displacement of PSD-95, and GluN2B mobilization (right). (B) Activation of mGluR5 stimulates PKC, which, via unknown mechanisms, induces Pyk2 autophosphorylation on Y402. Src binds to pY402 and increases NMDAR activity via unknown mechanisms that might be important for the stabilization of LTP during its first 2–3 min (Bartos et al, 2010). In the models to the left, without affecting Ca²⁺ influx, antibodies are hypothesized to prevent a conformational change in the GluN2B C-terminus, which in turn prevents binding of the CaMKII/CKII couple (A) or regulation of NMDAR by Pyk2/Src (B).