NMDA Receptor Phosphorylation at a Site Affected in Schizophrenia Controls Synaptic and Behavioral Plasticity

被引：28

作者：

Li, Bo ^{[3
]}

Devidze, Nino ^{[2
]}

Barengolts, Denis ^{[2
]}

Prostak, Naseem ^{[4
]}

Sphicas, Eleana ^{[2
]}

Apicella, Alfonso J. ^{[3
]}

Malinow, Roberto ^{[5
]}

Emamian, Effat S. ^{[1
,2
]}

机构：

[1] Adv Technol Novel Therapeut ATNT LLC, Newark, NJ 07103 USA

[2] Rockefeller Univ, New York, NY 10021 USA

[3] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[4] Cell & Mol Technol, Phillipsburg, NJ 08865 USA

[5] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

来源：

JOURNAL OF NEUROSCIENCE | 2009年 / 29卷 / 38期

基金：

美国国家卫生研究院;

关键词：

D-ASPARTATE RECEPTORS; ER RETENTION SIGNAL; PREPULSE INHIBITION; IN-VIVO; GLUTAMATE RECEPTORS; PSYCHOTIC SYMPTOMS; DOPAMINE NEURONS; BIPOLAR DISORDER; TEMPORAL CORTEX; D-SERINE;

D O I：

10.1523/JNEUROSCI.2109-09.2009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Phosphorylation of the NR1 subunit of NMDA receptors (NMDARs) at serine (S) 897 is markedly reduced in schizophrenia patients. However, the role of NR1 S897 phosphorylation in normal synaptic function and adaptive behaviors are unknown. To address these questions, we generated mice in which the NR1 S897 is replaced with alanine (A). This knock-in mutation causes severe impairment in NMDAR synaptic incorporation and NMDAR-mediated synaptic transmission. Furthermore, the phosphomutant animals have reduced AMPA receptor (AMPAR)-mediated synaptic transmission, decreased AMPAR GluR1 subunit in the synapse, and impaired long-term potentiation. Finally, the mutant mice exhibit behavioral deficits in social interaction and sensorimotor gating. Our results suggest that an impairment in NR1 phosphorylation leads to glutamatergic hypofunction that can contribute to behavioral deficits associated with psychiatric disorders.

引用

页码：11965 / 11972

页数：8

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