Long-term depression is independent of GluN2 subunit composition

Jonathan M. Wong, John Gray

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

NMDA receptors (NMDARs) mediate both long-term potentiation and long-term depression (LTD) and understanding how a single receptor can initiate both phenomena remains a major question in neuroscience. A prominent hypothesis implicates the NMDAR subunit composition, specifically GluN2A and GluN2B, in dictating the rules of synaptic plasticity. However, studies testing this hypothesis have yielded inconsistent and often contradictory results, especially for LTD. These inconsistent results may be due to challenges in the interpretation of subunit-selective pharmacology and in dissecting out the contributions of differential channel properties versus the interacting proteins unique to GluN2A or GluN2B. In this study, we address the pharmacological and biochemical challenges by using a single-neuron genetic approach to delete NMDAR subunits in conditional knock-out mice. In addition, the recently discovered non-ionotropic nature of NMDAR-dependent LTD allowed the rigorous assessment of unique subunit contributions to NMDAR-dependent LTD while eliminating the variable of differential charge transfer. Here we find that neither the GluN2A nor the GluN2B subunit is strictly necessary for either non-ionotropic or ionotropic LTD.

Original languageEnglish (US)
Pages (from-to)4462-4470
Number of pages9
JournalJournal of Neuroscience
Volume38
Issue number19
DOIs
StatePublished - May 9 2018

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N-Methyl-D-Aspartate Receptors
Pharmacology
Neuronal Plasticity
Long-Term Potentiation
Neurosciences
Knockout Mice
Neurons
Proteins

Keywords

  • LTD
  • Metabotropic
  • NR2A
  • NR2B
  • Signaling
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Long-term depression is independent of GluN2 subunit composition. / Wong, Jonathan M.; Gray, John.

In: Journal of Neuroscience, Vol. 38, No. 19, 09.05.2018, p. 4462-4470.

Research output: Contribution to journalArticle

Wong, Jonathan M. ; Gray, John. / Long-term depression is independent of GluN2 subunit composition. In: Journal of Neuroscience. 2018 ; Vol. 38, No. 19. pp. 4462-4470.
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