Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus

Grace France,Diego Fernández-Fernández,Erica S Burnell,Mark W Irvine,Daniel T Monaghan,David E Jane,Zuner A Bortolotto,Graham L Collingridge,Arturas Volianskis

doi:10.1016/j.neuropharm.2016.08.010

Abstract

In the CA1 area of the hippocampus N-methyl-d-aspartate receptors (NMDARs) mediate the induction of long-term depression (LTD), short-term potentiation (STP) and long-term potentiation (LTP). All of these forms of synaptic plasticity can be readily studied in juvenile hippocampal slices but the involvement of particular NMDAR subunits in the induction of these different forms of synaptic plasticity is currently unclear. Here, using NVP-AAM077, Ro 25-6981 and UBP145 to target GluN2A-, 2B- and 2D-containing NMDARs respectively, we show that GluN2B-containing NMDARs (GluN2B) are involved in the induction of LTD, STP and LTP in slices prepared from P14 rat hippocampus. A concentration of Ro (1 μM) that selectively blocks GluN2B-containing diheteromers is able to block LTD. It also inhibits a component of STP without affecting LTP. A higher concentration of Ro (10 μM), that also inhibits GluN2A/B triheteromers, blocks LTP. UBP145 selectively inhibits the Ro-sensitive component of STP whereas NVP inhibits LTP. These data are consistent with a role of GluN2B diheretomers in LTD, a role of both GluN2B- and GluN2D- containing NMDARs in STP and a role of GluN2A/B triheteromers in LTP.This article is part of the Special Issue entitled ‘Ionotropic glutamate receptors’.

Highlights

N-Methyl-D-aspartate receptors (NMDARs) are centrally involved in synaptic transmission, synaptic plasticity and learning and memory (Bliss and Collingridge, 2013; 1993; Volianskis et al, 2015)
Using NVPAAM077, Ro 25-6981 and UBP145 to target GluN2A, 2B- and 2D-containing N-methyl-D-aspartate receptors (NMDARs) respectively, we show that GluN2B-containing NMDARs (GluN2B) are involved in the induction of long-term depression (LTD), short-term potentiation (STP) and long-term potentiation (LTP) in slices prepared from P14 rat hippocampus
One suggestion that has gained considerable traction is that GluN2A-containing NMDARs are required for LTP and that GluN2B-containing NMDARs are involved in LTD (Bartlett et al, 2007; Köhr et al, 2003; Liu et al, 2004; Massey et al, 2004; Sakimura et al, 1995)

Summary

Introduction

N-Methyl-D-aspartate receptors (NMDARs) are centrally involved in synaptic transmission, synaptic plasticity and learning and memory (Bliss and Collingridge, 2013; 1993; Volianskis et al, 2015). The role of NMDAR’s in synaptic plasticity has been studied extensively (Collingridge et al, 1983; Tsien et al, 1996); there has been considerable disagreement about the involvement of specific receptor subtypes in both LTP and LTD (Bartlett et al, 2007; Berberich et al, 2005; Cull-Candy et al, 2001; Hrabetova et al, 2000; Li et al, 2007; Liu et al, 2004; Massey et al, 2004; Paoletti et al, 2013; Sakimura et al, 1995; Tang et al, 1999). There is considerable evidence that GluN2B-containing NMDARs are important for LTP (Barria and Malinow, 2005; Bartlett et al, 2007; Berberich et al, 2007; Tang et al, 1999) and the role of GluN2B-containing NMDARs in LTD has been challenged (Bartlett et al, 2007; Li et al, 2007; Morishita et al, 2007)

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