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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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’.

Original languageEnglish (US)
Pages (from-to)76-83
Number of pages8
JournalNeuropharmacology
Volume112
DOIs
StatePublished - Jan 1 2017

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Neuronal Plasticity
Long-Term Potentiation
N-Methyl-D-Aspartate Receptors
Hippocampus
Ionotropic Glutamate Receptors

Keywords

  • Long-term depression, LTD
  • Long-term potentiation, LTP
  • NMDA receptors
  • Short-term potentiation, STP

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

France, G., Fernández-Fernández, D., Burnell, E. S., Irvine, M. W., Monaghan, D. T., Jane, D. E., ... Volianskis, A. (2017). Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus. Neuropharmacology, 112, 76-83. https://doi.org/10.1016/j.neuropharm.2016.08.010

Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus. / France, Grace; Fernández-Fernández, Diego; Burnell, Erica S.; Irvine, Mark W.; Monaghan, Daniel T; Jane, David E.; Bortolotto, Zuner A.; Collingridge, Graham L.; Volianskis, Arturas.

In: Neuropharmacology, Vol. 112, 01.01.2017, p. 76-83.

Research output: Contribution to journalArticle

France, G, Fernández-Fernández, D, Burnell, ES, Irvine, MW, Monaghan, DT, Jane, DE, Bortolotto, ZA, Collingridge, GL & Volianskis, A 2017, 'Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus', Neuropharmacology, vol. 112, pp. 76-83. https://doi.org/10.1016/j.neuropharm.2016.08.010
France, Grace ; Fernández-Fernández, Diego ; Burnell, Erica S. ; Irvine, Mark W. ; Monaghan, Daniel T ; Jane, David E. ; Bortolotto, Zuner A. ; Collingridge, Graham L. ; Volianskis, Arturas. / Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus. In: Neuropharmacology. 2017 ; Vol. 112. pp. 76-83.
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AU - Fernández-Fernández, Diego

AU - Burnell, Erica S.

AU - Irvine, Mark W.

AU - Monaghan, Daniel T

AU - Jane, David E.

AU - Bortolotto, Zuner A.

AU - Collingridge, Graham L.

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AB - 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’.

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