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Eapen AV, Fernández-Fernández D, Georgiou J, et al. Multiple roles of GluN2D-containing NMDA receptors in short-term potentiation and long-term potentiation in mouse hippocampal slices. Neuropharmacology. 2021;201:108833doi: 10.1016/j.neuropharm.2021.108833.
Eapen, A. V., Fernández-Fernández, D., Georgiou, J., Bortolotto, Z. A., Lightman, S., Jane, D. E., Volianskis, A., & Collingridge, G. L. (2021). Multiple roles of GluN2D-containing NMDA receptors in short-term potentiation and long-term potentiation in mouse hippocampal slices. Neuropharmacology, 201108833. https://doi.org/10.1016/j.neuropharm.2021.108833
Eapen, Alen V, et al. "Multiple roles of GluN2D-containing NMDA receptors in short-term potentiation and long-term potentiation in mouse hippocampal slices." Neuropharmacology vol. 201 (2021): 108833. doi: https://doi.org/10.1016/j.neuropharm.2021.108833
Eapen AV, Fernández-Fernández D, Georgiou J, Bortolotto ZA, Lightman S, Jane DE, Volianskis A, Collingridge GL. Multiple roles of GluN2D-containing NMDA receptors in short-term potentiation and long-term potentiation in mouse hippocampal slices. Neuropharmacology. 2021 Dec 15;201:108833. doi: 10.1016/j.neuropharm.2021.108833. Epub 2021 Oct 09. PMID: 34637787; PMCID: PMC8607330.
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Neuropharmacology. 2021 Dec 15;201:108833. doi: 10.1016/j.neuropharm.2021.108833. Epub 2021 Oct 09.

Multiple roles of GluN2D-containing NMDA receptors in short-term potentiation and long-term potentiation in mouse hippocampal slices.

Neuropharmacology

Alen V Eapen, Diego Fernández-Fernández, John Georgiou, Zuner A Bortolotto, Stafford Lightman, David E Jane, Arturas Volianskis, Graham L Collingridge

Affiliations

  1. Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada. Electronic address: [email protected].
  2. Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
  3. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
  4. Bristol Medical School, University of Bristol, Bristol, UK.
  5. Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK; Bristol Medical School, University of Bristol, Bristol, UK; Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK.
  6. Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; TANZ Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.

PMID: 34637787 PMCID: PMC8607330 DOI: 10.1016/j.neuropharm.2021.108833

Abstract

The GluN2 subunits of N-methyl-d-aspartate receptors (NMDARs) are key drivers of synaptic plasticity in the brain, where the particular GluN2 composition endows the NMDAR complex with distinct pharmacological and physiological properties. Compared to GluN2A and GluN2B subunits, far less is known about the role of the GluN2D subunit in synaptic plasticity. In this study, we have used a GluN2C/2D selective competitive antagonist, UBP145, in combination with a GluN2D global knockout (GluN2D KO) mouse line to study the contribution of GluN2D-containing NMDARs to short-term potentiation (STP) and long-term potentiation (LTP) in the CA1 region of mouse hippocampal slices. We made several distinct observations: First, GluN2D KO mice have higher levels of LTP compared to wild-type (WT) mice, an effect that was occluded by blockade of GABA receptor-mediated inhibition or by using a strong LTP induction protocol. Second, UBP145 partially inhibited LTP in WT but not GluN2D KO mice. Third, UBP145 inhibited a component of STP, termed STP2, in WT but not GluN2D KO mice. Taken together, these findings suggest an involvement for GluN2D-containing NMDARs in both STP and LTP in mouse hippocampus.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keywords: GluN2D knockout mice; Hippocampus; LTP; Long-term potentiation; STP; Short-term potentiation

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