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Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators
Different types of memory are thought to rely on different types of synaptic plasticity, many of which depend on the activation of the N-Methyl-D Aspartate (NMDA) subtype of glutamate receptors. Accordingly, there is considerable interest in the possibility of using positive allosteric modulators (P...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Pergamon Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803579/ https://www.ncbi.nlm.nih.gov/pubmed/34678377 http://dx.doi.org/10.1016/j.neuropharm.2021.108840 |
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author | France, G. Volianskis, R. Ingram, R. Bannister, N. Rothärmel, R. Irvine, M.W. Fang, G. Burnell, E.S. Sapkota, K. Costa, B.M. Chopra, D.A. Dravid, S.M. Michael-Titus, A.T. Monaghan, D.T. Georgiou, J. Bortolotto, Z.A. Jane, D.E. Collingridge, G.L. Volianskis, A. |
author_facet | France, G. Volianskis, R. Ingram, R. Bannister, N. Rothärmel, R. Irvine, M.W. Fang, G. Burnell, E.S. Sapkota, K. Costa, B.M. Chopra, D.A. Dravid, S.M. Michael-Titus, A.T. Monaghan, D.T. Georgiou, J. Bortolotto, Z.A. Jane, D.E. Collingridge, G.L. Volianskis, A. |
author_sort | France, G. |
collection | PubMed |
description | Different types of memory are thought to rely on different types of synaptic plasticity, many of which depend on the activation of the N-Methyl-D Aspartate (NMDA) subtype of glutamate receptors. Accordingly, there is considerable interest in the possibility of using positive allosteric modulators (PAMs) of NMDA receptors (NMDARs) as cognitive enhancers. Here we firstly review the evidence that NMDA receptor-dependent forms of synaptic plasticity: short-term potentiation (STP), long-term potentiation (LTP) and long-term depression (LTD) can be pharmacologically differentiated by using NMDAR ligands. These observations suggest that PAMs of NMDAR function, depending on their subtype selectivity, might differentially regulate STP, LTP and LTD. To test this hypothesis, we secondly performed experiments in rodent hippocampal slices with UBP714 (a GluN2A/2B preferring PAM), CIQ (a GluN2C/D selective PAM) and UBP709 (a pan-PAM that potentiates all GluN2 subunits). We report here, for the first time, that: (i) UBP714 potentiates sub-maximal LTP and reduces LTD; (ii) CIQ potentiates STP without affecting LTP; (iii) UBP709 enhances LTD and decreases LTP. We conclude that PAMs can differentially regulate distinct forms of NMDAR-dependent synaptic plasticity due to their subtype selectivity. This article is part of the Neuropharmacology Special Issue on ‘Glutamate Receptors – NMDA receptors’. |
format | Online Article Text |
id | pubmed-8803579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Pergamon Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88035792022-02-03 Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators France, G. Volianskis, R. Ingram, R. Bannister, N. Rothärmel, R. Irvine, M.W. Fang, G. Burnell, E.S. Sapkota, K. Costa, B.M. Chopra, D.A. Dravid, S.M. Michael-Titus, A.T. Monaghan, D.T. Georgiou, J. Bortolotto, Z.A. Jane, D.E. Collingridge, G.L. Volianskis, A. Neuropharmacology Article Different types of memory are thought to rely on different types of synaptic plasticity, many of which depend on the activation of the N-Methyl-D Aspartate (NMDA) subtype of glutamate receptors. Accordingly, there is considerable interest in the possibility of using positive allosteric modulators (PAMs) of NMDA receptors (NMDARs) as cognitive enhancers. Here we firstly review the evidence that NMDA receptor-dependent forms of synaptic plasticity: short-term potentiation (STP), long-term potentiation (LTP) and long-term depression (LTD) can be pharmacologically differentiated by using NMDAR ligands. These observations suggest that PAMs of NMDAR function, depending on their subtype selectivity, might differentially regulate STP, LTP and LTD. To test this hypothesis, we secondly performed experiments in rodent hippocampal slices with UBP714 (a GluN2A/2B preferring PAM), CIQ (a GluN2C/D selective PAM) and UBP709 (a pan-PAM that potentiates all GluN2 subunits). We report here, for the first time, that: (i) UBP714 potentiates sub-maximal LTP and reduces LTD; (ii) CIQ potentiates STP without affecting LTP; (iii) UBP709 enhances LTD and decreases LTP. We conclude that PAMs can differentially regulate distinct forms of NMDAR-dependent synaptic plasticity due to their subtype selectivity. This article is part of the Neuropharmacology Special Issue on ‘Glutamate Receptors – NMDA receptors’. Pergamon Press 2022-01-01 /pmc/articles/PMC8803579/ /pubmed/34678377 http://dx.doi.org/10.1016/j.neuropharm.2021.108840 Text en © 2022 The Authors. Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article France, G. Volianskis, R. Ingram, R. Bannister, N. Rothärmel, R. Irvine, M.W. Fang, G. Burnell, E.S. Sapkota, K. Costa, B.M. Chopra, D.A. Dravid, S.M. Michael-Titus, A.T. Monaghan, D.T. Georgiou, J. Bortolotto, Z.A. Jane, D.E. Collingridge, G.L. Volianskis, A. Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators |
title | Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators |
title_full | Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators |
title_fullStr | Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators |
title_full_unstemmed | Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators |
title_short | Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators |
title_sort | differential regulation of stp, ltp and ltd by structurally diverse nmda receptor subunit-specific positive allosteric modulators |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803579/ https://www.ncbi.nlm.nih.gov/pubmed/34678377 http://dx.doi.org/10.1016/j.neuropharm.2021.108840 |
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