AMPA receptors: potential implications in development and disease

α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors are one type of ionotropic glutamate receptor involved in rapid excitatory synaptic transmission. AMPA receptors have been increasingly implicated in long-term potentiation, and recent evidence suggests that they may play a role in disorders affecting the nervous system. The finding that early in postnatal development AMPA receptors are not expressed has lately been the focus of much attention. Resolving the factors involved in AMPA receptor expression suggests that their induction is a developmentally regulated process with the possibility that alterations in receptor expression may be correlated with pathology in neurological disorders. This paper provides an overview of factors involved in AMPA receptor induction as well as of their role in plasticity and neuronal pathologies. Received 5 December 2000; received after revision 12 January 2001; accepted 2 February 2001     

Mechanisms of synaptic depression triggered by metabotropic glutamate receptors

Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a reduction of synaptic efficacy at many synapses. These forms of synaptic plasticity are referred to as long-term depression (mGluR-LTD). We will distinguish between mGluR-LTD induced by pre- or postsynaptic receptors and mGluR-LTD induced by the locus of the expression mechanism of the synaptic depression. We will also review recent evidence that mGluR-mediated responses themselves are subject to depression, which may constitute a form of metaplasticity. Received 13 May 2008; received after revision 07 July 2008; accepted 11 July 2008     

Aniracetam对小白鼠被动回避反应的影响

本文建立了被动回避行为的实验模型，并用此模型观察了Ａｎｉｒａｃｅｔａｍ对小白鼠被动回避行为的建立，保持和消退的影响，结果表明Ａｎｉｒａｃｅｔａｍ对被动回避行为的建立没有明显的影响，在行为的保持和消退过程中，则有明显的延缓作用，Ａｎｉｒａｃｅｔａｍ对正常动物记忆的保存有效。     

突触骨架重塑调控吗啡戒断负性记忆的分子机制进展简

成瘾性药物戒断所产生的负性情绪记忆被认为是导致强迫性用药的主要原因. 戒断会引起相关脑区发生诸如突触传递和神经结构可塑性等适应性变化,这种适应性变化最终会引起病理性记忆的形成. 研究表明,肌动蛋白actin骨架重塑与突触可塑性以及记忆的形成关系密切,然而对其调控记忆的分子机制知之甚少. 最近,本研究小组围绕吗啡戒断负性情绪记忆的形成机制展开研究,在整体水平上阐述了突触骨架actin及其一系列下游信号参与调控吗啡戒断负性记忆的分子机制. 本文将讨论近年来突触结构可塑性参与调控成瘾性药物负性记忆形成的最新进展,着重探讨阿片类物质成瘾负性动机的形成机制,有助于深入了解成瘾形成的分子机制,为成瘾的研究和治疗提供新思路.     

谷氨酸AMPA受体拮抗剂CNQX对大鼠颠倒学习的影响

研究利用旋转T迷宫装置,通过食物强化,分别训练大鼠视觉辨别学习和颠倒学习任务;每次训练前均向动物腹腔注射20μg/kg的谷氨酸AMPA受体拮抗剂CNQX,以考察其对大鼠学习能力的影响.结果发现,CNQX并不影响正常学习,但对于颠倒学习,CNQX注射组的学习次数较控制组显著增加,说明CNQX可以对大鼠的认知灵活性造成损害.     

Intracellular trafficking of AMPA receptors in synaptic plasticity

Modification of ligand-gated receptor function at the postsynaptic domain is one of the most important mechanisms by which the efficacy of synaptic transmission in the nervous system is regulated. Traditionally, these types of modifications have been thought to be achieved mainly by altering the channel-gating properties or conductance of the receptors. However, recent evidence suggests that AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxayolepropionic acid)-type ligand-gated glutamate receptors are continuously recycling between the plasma membrane and the intracellular compartments via vesicle-mediated plasma membrane insertion and clathrin-dependent endocytosis. Regulation of either receptor insertion or endocytosis results in a rapid change in the number of these receptors expressed on the plasma membrane surface and in the receptor-mediated responses, thereby playing an important role in mediating certain forms of synaptic plasticity. Thus, controlling the number of postsynaptic receptors by regulating the intracellular trafficking and plasma membrane expression of the postsynaptic receptors may be a common and important mechanism of synaptic plasticity in the mammalian central nervous system.