在哺乳动物大脑中，AMPA型谷氨酸受体是主要的兴奋性突触后受体介导了快速的神经传递和突触可塑性。ABHD6，一种单酰基甘油酯酶，是AMPA受体大分子复合物中的一种组分。前期的研究发现ABHD6可以影响AMPA受体在膜上的表达及其通道动力学，在神经元中调控ABHD6的表达可以显著的负向调节AMPA受体介导的兴奋性突触传递；这些作用与ABHD6的酶活性无关。至今尚无ABHD6缺失的动物模型报道，它是否可以在在体水平上影响AMPA受体的转运和功能尚不可知。申请人计划建立ABHD6缺失的小鼠动物模型，运用行为学、电生理、免疫组化、生物化学等手段对ABHD6如何影响AMPA型谷氨酸受体的在体功能进行研究，围绕‘ABHD6蛋白缺失对AMPA型谷氨酸受体功能及依赖的突触可塑性的影响’这个中心问题，重点研究ABHD6蛋白缺失对AMPA受体功能及依赖的突触可塑性的影响，加深对AMPA受体转运和上膜的理解。

In the brain, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors are major postsynaptic receptors at excitatory synapses, mediating fast neurotransmission and synaptic plasticity. α/β-hydrolase domain-containing 6 (ABHD6), a monoacylglycerol lipase, was previously found to be a component of AMPA receptor (AMPAR) macromolecular complexes. Our previous study show that ABHD6 regulates the surface delivery and kinetics of AMPA receptors, and ABHD6 significantly negative regulate AMPA receptor-mediated excitatory synapse transmission in hippocampal neurons; interestingly, these effects are independent of the monoacylglycerol lipase activity. So far there is no loss-of-function animal model for ABHD6, thus it is unclear whether ABHD6 regulates AMPA receptors function in vivo. Here we plan to develop ABHD6 conventional and conditional knockout mouse model. We will use behavior, electrophysiology, immunohistochemistry and biochemistry approaches to investigate how ABHD6 affect the function of AMPA receptors in vivo. We anticipate that this work would improve our understanding of dynamic regulation of AMPA receptors at synapses.