Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression

By P. Massey, Ben Johnson, P. Moult, Y. Auberson, Malcolm W. Brown, E. Molnár, G. Collingridge, Z. Bashir. Journal of Neuroscience, 2004

743 citations recorded by the source corpus.

It is widely believed that long-term depression (LTD) and its counterpart, long-term potentiation (LTP), involve mechanisms that are crucial for learning and memory. However, LTD is difficult to induce in adult cortex for reasons that are not known. Here we show that LTD can be readily induced in adult cortex by the activation of NMDA receptors (NMDARs), after inhibition of glutamate uptake. Interestingly there is no need to activate synaptic NMDARs to induce this LTD, suggesting that LTD is triggered primarily by extrasynaptic NMDA receptors. We also find that de novo LTD requires the activation of NR2B-containing NMDAR, whereas LTP requires activation of NR2A-containing NMDARs. Surprisingly another form of LTD, depotentiation, requires activation of NR2A-containing NMDARs. Therefore, NMDARs with different synaptic locations and subunit compositions are involved in various forms of synaptic plasticity in adult cortex.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/0ad923b911dde80c839a5e222e0a4bbb7597a98c

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Citations in the corpus

Distinct Roles of NR2A and NR2B Cytoplasmic Tails in Long-Term (2010, neutral): “Some studies in hippocampus and perirhinal cortex showed that ifenprodil and Ro25-6981 block LTD but not LTP (Liu et al., 2004; Massey et al., 2004; Fox et al., 2006; Izumi et al., 2006; Chen et al., 2007), whereas NVP-AAM077 blocks LTP but not LTD (Liu et al.”
Activation of p75NTR by proBDNF facilitates hippocampal long-term depression (2005, background): “Furthermore, we show that this enhancement of LTD by proBDNF-p75 NTR is mediated through an upregulation of NR2B, an NMDA receptor subtype uniquely involved in LT”
Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors (2011, methodology): “1B), which have been reported to have no (Massey et al., 2004; Hu et al., 2009) or only partial (Berberich et al., 2007) effects on LTP, were added to the perfusion solution before 7PA2 or CHO CM application.”
Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists. (2012, background): “We next assessed the involvement of those receptors in LTD induced by a low frequency stimulation protocol (Figures 6B1 and 6C).”
Regulation of NMDA Receptor Subunit Expression and Its Implications for LTD, LTP, and Metaplasticity (2008, methodology): “For example, in the adult perirhinal cortex, the ifenprodil-dependence of LTD relies on the state of the synapse (Massey et al., 2004); ifenprodil blocks LTD that has been induced at a basal state, but the antagonist fails to block depotentiation (a form of LTD induced at recently potentiated synaps”
Astrocyte control of synaptic transmission and neurovascular coupling. (2006, background): “Their results provide the exciting observation that the astrocyte controls a form of metaplasticity: whether a synapse exhibits LTP or LTD is controlled by the glial coverage of the synapse and the extent to which D-serine is provided to synaptic NMDARs.”
NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. (2005, neutral): “While recent studies propose that activation of NR2A receptors solely controls induction of LTP (Liu et al., 2004; Massey et al., 2004), this view has been challenged (Berberich et al.”
Excitotoxicity and stroke: identifying novel targets for neuroprotection. (2014, neutral): “the LTP and the GluN2BR subtype mediating the LTD (Dalton et al., 2012; Foster et al., 2010; Fox et al., 2006; Li et al., 2006; Liu et al., 2004; Massey et al., 2004) (but see also Berberich et al.”
Glutamate Receptor Ion Channels: Structure, Regulation, and Function (2010, methodology): “…receptors over GluN2B-containing receptors, was used to evaluate physiological roles of GluN2A and GluN2B in rodent models of synaptic plasticity and neurotoxicity before a full pharmacological characterization was completed (Liu et al., 2004b; Massey et al., 2004; Zhou and Baudry, 2006).”
Regulation of extrasynaptic signaling by polysialylated NCAM: Impact for synaptic plasticity and cognitive functions (2017, background): “Previous studies also suggested that activation of GluN2A-NMDARs might preferentially promote the induction of LTP, while GluN2B-contianing NMDARs mediate the induction of LTD (Liu et al., 2004; Massey et al., 2004; Papouin et al., 2012).”
NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death Both In Vitro and In Vivo (2007, background): “However, several recent studies have demonstrated that such a marginal effect may not significantly alter the utility of NVPAAM077 as an NR2A-subunit preferential antagonist under experimental conditions such as in the present study (Liu et al., 2004; Massey et al., 2004; Tigaret et al., 2006).”