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首页> 外文期刊>The European Journal of Neuroscience >GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system
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GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system

机译：GABAA受体与中枢神经系统抑制性神经传递的可塑性

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GABAA receptors (GABAARs) are ligand-gated Cl- channels that mediate most of the fast inhibitory neurotransmission in the central nervous system (CNS). Multiple GABAAR subtypes are assembled from a family of 19 subunit genes, raising the question of the significance of this heterogeneity. In this review, we discuss the evidence that GABAAR subtypes represent distinct receptor populations with a specific spatio-temporal expression pattern in the developing and adult CNS, being endowed with unique functional and pharmacological properties, as well as being differentially regulated at the transcriptional, post-transcriptional and translational levels. GABAAR subtypes are targeted to specific subcellular domains to mediate either synaptic or extrasynaptic transmission, and their action is dynamically regulated by a vast array of molecular mechanisms to adjust the strength of inhibition to the changing needs of neuronal networks. These adaptations involve not only changing the gating or kinetic properties of GABAARs, but also modifying the postsynaptic scaffold organised by gephyrin to anchor specific receptor subtypes at postsynaptic sites. The significance of GABAAR heterogeneity is particularly evident during CNS development and adult neurogenesis, with different receptor subtypes fulfilling distinct steps of neuronal differentiation and maturation. Finally, analysis of the specific roles of GABAAR subtypes reveals their involvement in the pathophysiology of major CNS disorders, and opens novel perspectives for therapeutic intervention. In conclusion, GABAAR subtypes represent the substrate of a multifaceted inhibitory neurotransmission system that is dynamically regulated and performs multiple operations, contributing globally to the proper development, function and plasticity of the CNS.
机译：GABAA受体（GABAAR）是配体门控的Cl-通道，可介导中枢神经系统（CNS）中的大多数快速抑制性神经传递。从19个亚基基因家族中组装了多种GABAAR亚型，这引发了这种异质性重要性的问题。在这篇综述中，我们讨论了以下证据：GABAAR亚型代表发育中和成年中枢神经系统中具有特定时空表达模式的独特受体群，具有独特的功能和药理特性，并且在转录后-转录和翻译水平。 GABAAR亚型靶向特定的亚细胞结构域，以介导突触或突触外传递，其作用受多种分子机制动态调节，以调节抑制强度，以适应神经网络不断变化的需求。这些适应不仅涉及改变GABAARs的门控或动力学特性，而且还修饰了由gephyrin组织的突触后支架，以将特定的受体亚型锚定在突触后位点。 GABAAR异质性的重要性在中枢神经系统发育和成年神经发生过程中尤其明显，其中不同的受体亚型完成神经元分化和成熟的不同步骤。最后，对GABAAR亚型的特定作用的分析揭示了它们参与主要中枢神经系统疾病的病理生理，并为治疗干预开辟了新的前景。总之，GABAAR亚型代表了一个多面抑制性神经传递系统的底物，该系统被动态调节并执行多种操作，为CNS的正确发育，功能和可塑性做出了全球性贡献。

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