Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators.
Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators.
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DOI：
10.1016/j.neuropharm.2021.108840
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发表时间：
2022-01-01
影响因子：
4.7
通讯作者：
Volianskis A
中科院分区：
文献类型：
--
作者：
France G;Volianskis R;Ingram R;Bannister N;Rothärmel R;Irvine MW;Fang G;Burnell ES;Sapkota K;Costa BM;Chopra DA;Dravid SM;Michael-Titus AT;Monaghan DT;Georgiou J;Bortolotto ZA;Jane DE;Collingridge GL;Volianskis A
人们认为不同类型的记忆依赖于不同类型的突触可塑性，其中许多依赖于谷氨酸受体 N-甲基-D 天冬氨酸 (NMDA) 亚型的激活。因此，人们对使用 NMDA 受体 (NMDAR) 的正变构调节剂 (PAM) 作为认知增强剂的可能性非常感兴趣。在这里，我们首先回顾了 NMDA 受体依赖性突触可塑性形式：短期增强（STP）、长期增强（LTP）和长期抑制（LTD）可以通过使用 NMDAR 配体在药理学上区分的证据。这些观察结果表明，NMDAR 功能的 PAM 根据其亚型选择性，可能会差异性地调节 STP、LTP 和 LTD。为了验证这一假设，我们随后在啮齿动物海马切片中用 UBP714（一种 GluN2A/2B 优先的 PAM）、CIQ（一种 GluN2C/D 选择性 PAM）和 UBP709（一种增强所有 GluN2 亚基的泛 PAM）进行了实验。我们在此首次报告：(i) UBP714 增强次最大 LTP 并降低 LTD； (ii) CIQ 增强 STP 而不影响 LTP； (iii) UBP709 增强 LTD 并降低 LTP。我们得出的结论是，由于 PAM 的亚型选择性，可以差异化地调节 NMDAR 依赖性突触可塑性的不同形式。本文是“谷氨酸受体 - NMDA 受体”神经药理学特刊的一部分。 NMDAR 依赖性 STP、LTP 和 LTD 可通过药理学解离 GluN2A/2B PAM UBP714 增强 LTP 并降低 LTD GluN2C/D PAM CIQ 增强 STP，而不影响 LTP NMDAR pan-PAM UBP709 增强 LTD 并降低 LTP
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’. NMDAR-dependent STP, LTP and LTD can be dissociated pharmacologically GluN2A/2B PAM UBP714 potentiates LTP and reduces LTD GluN2C/D PAM CIQ potentiates STP without affecting LTP NMDAR pan-PAM UBP709 potentiates LTD and reduces LTP
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影响因子：
2.5
作者：
Chen, HX;Otmakhov, N;Lisman, J
通讯作者：
Lisman, J
影响因子：
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作者：
Chen, Rong-Qing;Wang, Shan-Hui;Lu, Wei
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Lu, Wei
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Bartlett, Thomas E.;Lu, Jie;Wang, Yu Tian
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Wang, Yu Tian
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作者：
Cameron, Krasnodara;Bartle, Emily;Gentile, Lisa
通讯作者：
Gentile, Lisa
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作者：
Anderson, William W.;Collingridge, Graham L.
通讯作者：
Collingridge, Graham L.