Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors
Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors
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DOI：
10.1073/pnas.95.12.7097
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发表时间：
1998-06-09
影响因子：
11.1
通讯作者：
von Zastrow, M
中科院分区：
文献类型：
--
作者：
Lissin, DV;Gomperts, SN;von Zastrow, M
谷氨酸受体的不同亚型通常共定位于哺乳动物大脑中的单个兴奋性突触，似乎具有不同的功能。为了解决神经元活动是否可以差异调节两种特定亚型的离子型谷氨酸受体的突触表面表达，我们将AMPA（α-氨基-3-羟基-5-甲基异恶唑-4-丙酸）受体亚基（GluR 1）和NMDA（N-甲基-D-天冬氨酸）受体亚单位（NR 1）的重组腺病毒载体在培养的海马神经元中表达，这两种受体亚型都适当地靶向突触质膜，如通过与突触囊泡蛋白突触素共定位所定义的。通过用γ-氨基丁酸A型受体拮抗剂印防己毒素长时间阻断抑制性突触来增加培养细胞网络的活性，导致突触处GluR 1而非NR 1的表面表达的活性依赖性和NMDA受体依赖性降低，与这一观察结果一致，相对于内源性AMPA受体，对未感染培养物的相同处理减少了内源性AMPA受体对突触电流的贡献。这些结果表明，神经元活动可以差异调节AMPA和NMDA受体在单个突触的表面表达。
Distinct subtypes of glutamate receptors often are colocalized at individual excitatory synapses in the mammalian brain get appear to subserve distinct functions. To address whether neuronal activity may differentially regulate the surface expression at synapses of two specific subtypes of ionotropic glutamate receptors we epitope-tagged an AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subunit (GluR1) and an NMDA (N-methyl-D-aspartate) receptor subunit (NR1) on their extracellular termini and expressed these proteins in cultured hippocampal neurons using recombinant adenoviruses, Both receptor subtypes were appropriately targeted to the synaptic plasma membrane as defined by colocalization with the synaptic vesicle protein synaptophysin. Increasing activity in the network of cultured cells by prolonged blockade of inhibitory synapses with the gamma-aminobutyric acid type A receptor antagonist picrotoxin caused an activity-dependent and NMDA receptor-dependent decrease in surface expression of GluR1, but not NR1, at synapses, Consistent with this observation identical treatment of noninfected cultures decreased the contribution of endogenous AMPA receptors to synaptic currents relative to endogenous NMDA receptors, These results indicate that neuronal activity can differentially regulate the surface expression of AMPA and NMDA receptors at individual synapses.