NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus

被引：534

作者：

Lee, HK

Kameyama, K

Huganir, RL

Bear, MF ^{[1
]}

机构：

[1] Brown Univ, Dept Neurosci, Howard Hughes Med Inst, Providence, RI 02912 USA

[2] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Neurosci, Baltimore, MD 21205 USA

来源：

NEURON | 1998年 / 21卷 / 05期

关键词：

D O I：

10.1016/S0896-6273(00)80632-7

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Brief bath application of N-methyl-D-aspartate (NMDA) to hippocampal slices produces long-term synaptic depression (LTD) in CA1 that is (1) sensitive to postnatal age, (2) saturable, (3) induced postsynaptically, (4) reversible, and (5) not associated with a change in paired pulse facilitation. Chemically induced LTD (Chem-LTD) and homosynaptic LTD are mutually occluding, suggesting a common expression mechanism. Using phosphorylation site-specific antibodies, we found that induction of chem-LTD produces a persistent dephosphorylation of the GluR1 subunit of AMPA receptors at serine 845, a cAMP-dependent protein kinase (PKA) substrate, but not at serine 831, a substrate of protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase II (CaMKII). These results suggest that dephosphorylation of AMPA receptors is an expression mechanism for LTD and indicate an unexpected role of PKA in the postsynaptic modulation of excitatory synaptic transmission.

引用

页码：1151 / 1162

页数：12

共 55 条

[1] Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor [J].