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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pergamon Press 2022
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’.
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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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