Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression

Peter V. Massey, Benjamin E. Johnson, Peter R. Moult, Yves P. Auberson, Malcolm W. Brown, Elek Molnar, Graham L. Collingridge, Zafar I. Bashir

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)7821-7828
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number36
DOIs
Publication statusPublished - 8 Sep 2004

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Long-Term Potentiation
Depression
N-Methyl-D-Aspartate Receptors
Long-Term Synaptic Depression
Neurotransmitter Receptor
Neuronal Plasticity
NR2B NMDA receptor
Glutamic Acid
Learning

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Massey, P. V., Johnson, B. E., Moult, P. R., Auberson, Y. P., Brown, M. W., Molnar, E., ... Bashir, Z. I. (2004). Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. Journal of Neuroscience, 24(36), 7821-7828. https://doi.org/10.1523/JNEUROSCI.1697-04.2004
Massey, Peter V. ; Johnson, Benjamin E. ; Moult, Peter R. ; Auberson, Yves P. ; Brown, Malcolm W. ; Molnar, Elek ; Collingridge, Graham L. ; Bashir, Zafar I. / Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 36. pp. 7821-7828.
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Massey, PV, Johnson, BE, Moult, PR, Auberson, YP, Brown, MW, Molnar, E, Collingridge, GL & Bashir, ZI 2004, 'Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression', Journal of Neuroscience, vol. 24, no. 36, pp. 7821-7828. https://doi.org/10.1523/JNEUROSCI.1697-04.2004

Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. / Massey, Peter V.; Johnson, Benjamin E.; Moult, Peter R.; Auberson, Yves P.; Brown, Malcolm W.; Molnar, Elek; Collingridge, Graham L.; Bashir, Zafar I.

In: Journal of Neuroscience, Vol. 24, No. 36, 08.09.2004, p. 7821-7828.

Research output: Contribution to journalArticle

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AU - Massey, Peter V.

AU - Johnson, Benjamin E.

AU - Moult, Peter R.

AU - Auberson, Yves P.

AU - Brown, Malcolm W.

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AU - Collingridge, Graham L.

AU - Bashir, Zafar I.

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AB - 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.

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