Metaplasticity gated through differential regulation of GluN2A versus GluN2B receptors by Src family kinases

被引：65

作者：

Yang, Kai ^{[2
]}

Trepanier, Catherine ^{[3
]}

Sidhu, Bikram ^{[2
]}

Xie, Yu-Feng ^{[1
,4
]}

Li, Hongbin ^{[2
]}

Lei, Gang ^{[1
,4
]}

Salter, Michael W. ^{[5
]}

Orser, Beverley A. ^{[2
]}

Nakazawa, Takanobu ^{[6
]}

Yamamoto, Tadashi ^{[6
]}

Jackson, Michael F. ^{[1
,4
]}

MacDonald, John F. ^{[1
,2
,3
,4
]}

机构：

[1] Robarts Res Inst, Mol Brain Res Grp, London, ON N6A 5K8, Canada

[2] Univ Toronto, Dept Physiol, Toronto, ON, Canada

[3] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada

[4] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada

[5] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada

[6] Univ Tokyo, Inst Med Sci, Div Oncol, Tokyo, Japan

来源：

EMBO JOURNAL | 2012年 / 31卷 / 04期

关键词：

NMDA receptors; Src kinases; synaptic plasticity; NR2B-CONTAINING NMDA RECEPTORS; LONG-TERM POTENTIATION; EXCITATORY SYNAPTIC-TRANSMISSION; TYROSINE PHOSPHORYLATION; SUBUNIT COMPOSITION; NR2B SUBUNIT; HIPPOCAMPAL; ACTIVATION; PLASTICITY; SYNAPSES;

D O I：

10.1038/emboj.2011.453

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Metaplasticity is a higher form of synaptic plasticity that is essential for learning and memory, but its molecular mechanisms remain poorly understood. Here, we report that metaplasticity of transmission at CA1 synapses in the hippocampus is mediated by Src family kinase regulation of NMDA receptors (NMDARs). We found that stimulation of G-protein-coupled receptors (GPCRs) regulated the absolute contribution of GluN2A-versus GluN2B-containing NMDARs in CA1 neurons: pituitary adenylate cyclase activating peptide 1 receptors (PAC1Rs) selectively recruited Src kinase, phosphorylated GluN2ARs, and enhanced their functional contribution; dopamine 1 receptors (D1Rs) selectively stimulated Fyn kinase, phosphorylated GluN2BRs, and enhanced these currents. Surprisingly, PAC1R lowered the threshold for long-term potentiation while long-term depression was enhanced by D1R. We conclude that metaplasticity is gated by the activity of GPCRs, which selectively target subtypes of NMDARs via Src kinases. The EMBO Journal (2012) 31, 805-816. doi: 10.1038/emboj.2011.453; Published online 20 December 2011

引用

页码：805 / 816

页数：12

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