在培养的海马神经元中，微小兴奋性突触后电流（mEPSCs）长时程增强（LTP）过程中，AMPA受体插入需要PI3激酶的激活。

Activation of PI3-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons.

作者信息

Man Heng-Ye, Wang Qinhua, Lu Wei-Yang, Ju William, Ahmadian Gholamreza, Liu Lidong, D'Souza Sandra, Wong T P, Taghibiglou C, Lu Jie, Becker Larry E, Pei Lin, Liu Fang, Wymann Matthias P, MacDonald John F, Wang Yu Tian

机构信息

Brain and Behavior Program and Department of Pathology, Research Institute of the Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5S 1A8.

出版信息

Neuron. 2003 May 22;38(4):611-24. doi: 10.1016/s0896-6273(03)00228-9.

DOI:10.1016/s0896-6273(03)00228-9

PMID:12765612

Abstract

Hippocampal CA1 homosynaptic long-term potentiation (LTP) is expressed specifically at activated synapses. Increased insertion of postsynaptic alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) appears to be crucial for CA1 LTP. However, the mechanism underlying AMPAR insertion during LTP remains largely unknown. We now report that phosphatidylinositol 3-kinase (PI3K) is complexed with AMPARs at synapses and activated by selective stimulation of synaptic N-methyl-D-aspartate (NMDA) receptors. Activation of the AMPAR-associated PI3K is required for the increased cell surface expression of AMPARs and LTP. Thus, our results strongly suggest that the AMPAR-PI3K complex may constitute a critical molecular signal responsible for AMPAR insertion at activated CA1 synapses during LTP, and consequently, this lipid kinase may serve to determine the polarity of NMDA receptor-dependent synaptic plasticity.

摘要

海马体CA1区的同突触长时程增强（LTP）特异性地在激活的突触处表达。突触后α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体（AMPARs）插入增加似乎对CA1区LTP至关重要。然而，LTP期间AMPAR插入的潜在机制在很大程度上仍然未知。我们现在报告，磷脂酰肌醇3-激酶（PI3K）在突触处与AMPARs形成复合物，并通过选择性刺激突触N-甲基-D-天冬氨酸（NMDA）受体而被激活。AMPAR相关PI3K的激活是AMPARs细胞表面表达增加和LTP所必需的。因此，我们的结果强烈表明，AMPAR-PI3K复合物可能构成一个关键的分子信号，负责LTP期间激活的CA1突触处的AMPAR插入，因此，这种脂质激酶可能有助于确定NMDA受体依赖性突触可塑性的极性。