AMPA受体是一种以谷氨酸为配体的离子通道，介导了哺乳动物脑中主要的快速兴奋性突触传递。AMPA受体的功能受转录后调控、翻译后修饰和AMPA受体复合物中辅助亚基的调节。这些辅助亚基能够和AMPA受体的核心亚基相互作用，并调节AMPA受体的转运、药理学特性和通道动力学。新的高分辨率蛋白质组学技术发现了一系列新的AMPA受体辅助亚基。申请人前期的研究发现，新发现的辅助亚基中的ABHD6是一种负向调控分子，它可以显著抑制AMPA受体的转运。但是ABHD6是否也参与调控AMPA受体的通道动力学和药理学特性目前尚不清楚。鉴于此一现状，申请人将通过ABHD6过表达或者基因敲除，在异源细胞和原代培养海马神经元体系中，深入系统地研究ABHD6对AMPA受体的动力学特性和药理学特性的调控作用，从而补足对ABHD6对整体AMPA受体功能的影响的认知，对更好地理解AMPA受体的调控和生物学功能具有重要意义。

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are glutamate-gated ion channels. They mediate the great majority of fast excitatory synaptic transmission in the mammalian brain and are absolutely critical for brain function. Regulation of AMPA receptor (AMPAR)-mediated synaptic transmission is a key mechanism for synaptic plasticity. The function of AMPARs can be regulated by RNA splicing and editing, posttranslational modifications, and auxiliary AMPAR binding subunits. These subunits play important roles in regulating the trafficking、kinetics and pharmacology of AMPA receptors. High-resolution proteomics analysis revealed a number of new AMPAR auxiliary subunits. Our previous studies shows that ABHD6 negatively regulates AMPAR-mediated synaptic transmission and AMPAR trafficking. But whether ABHD6 also involved in the regulation of AMPAR kinetics and pharmacology is still unknown. Here we plan to do electrophysiology recordings in both heterologous cells system that expressing ABHD6 and AMPARs, and cultured hippocampus neurons system that either overexpression ABHD6 or knockout ABHD6, to investigate how ABHD6 affect the kinetics and pharmacology of AMPA receptors. We anticipate that this work would complete our knowledge of the regulation of AMPA receptors through ABHD6, and improve our understanding of dynamic regulation of AMPA receptors.