AMPA受体成像与突触可塑性

Imaging of AMPA receptors and synaptic plasticity

在中枢神经系统中,α-氨基-3-羟基-5-甲基-4-异唑丙酸(AMPA)型谷氨酸受体介导大部分快速兴奋性神经突触传递,受体插入和离开突触的转运过程高度动态化,该过程的调节对多种形式的突触可塑性起至关重要的作用。而突触可塑性被认为是包括学习、记忆在内的大脑高级认知行为的关键分子机制。研究表明,当AMPA受体或调控AMPA受体转运的蛋白发生遗传突变时,会导致各种各样的疾病,包括自闭症、精神分裂症、阿尔茨海默病以及智力障碍等疾病。因此,阐明AMPA受体转运和功能的调控对于理解大脑高级功能有重要意义。以前研究结果表明,利用连有荧光蛋白标签的AMPA受体,可以直接观察到受体在膜上的转移过程。大多数研究是在体外的原代神经元培养或急性脑片上进行的,令人欣喜的是,最近,活体内突触蛋白的可视化得以实现,为研究突触可塑性提供了崭新的手段。本文主要讨论AMPA受体转运领域的重要发现,阐述体外成像和体内成像技术的发展对突触可塑性研究的贡献,并对该领域未来的发展进行展望。

In the central nervous system, ionotropic AMPA receptors mediate the majority of the fast excitatory synaptic transmission. Trafficking of AMPA receptors into and out of synapses is a highly dynamic process, which plays a key role in synaptic plasticity that is critical for higher brain functions such as learning and memory. Genetic alterations in AMPA receptor or proteins that regulate AMPA receptors trafficking have been implicated in various diseases, including autism spectrum disorders,schizophrenia, Alzheimer′s disease, and intellectual disability. Thus, elucidating the regulation of AMPA trafficking and function is vital to understanding higher brain functions. Many studies have used live imaging of fluorescently tagged AMPA receptors to directly monitor their membrane trafficking in real time, but most of these studies were performed in vitro using neuronal cell cultures or brain slices. Recent technological advances have allowed the imaging of synaptic proteins in vivo in intact organisms,which enables the visualization of synaptic plasticity at a molecular level in living animals. In this review,we mainly discuss the latest development in AMPA receptors trafficking studies and elucidate the contributions of receptor imaging in vitro and in vivo to understanding the molecular mechanisms underlying synaptic plasticity.