Muscle dystrophin–glycoprotein complex (DGC) links the intracellular cytoskeleton to the extracellular matrix. In neurons, dystroglycan and dystrophin, two major components of the DGC, localize in a subset of GABAergic synapses, where their function is unclear. Here we used mouse models to analyze the specific role of the DGC in the organization and function of inhibitory synapses. Loss of full-length dystrophin in mdx mice resulted in a selective depletion of the transmembrane β-dystroglycan isoform from inhibitory post-synaptic sites in cerebellar Purkinje cells. Remarkably, there were no differences in the synaptic distribution of the extracellular α-dystroglycan subunit, of GABA_A receptors and neuroligin 2. In contrast, conditional deletion of the dystroglycan gene from Purkinje cells caused a disruption of the DGC and severely impaired post-synaptic clustering of neuroligin 2, GABA_A receptors and scaffolding proteins. Accordingly, whole-cell patch-clamp analysis revealed a significant reduction in the frequency and amplitude of spontaneous IPSCs recorded from Purkinje cells. In the long-term, deletion of dystroglycan resulted in a significant decrease of GABAergic innervation of Purkinje cells and caused an impairment of motor learning functions. These results show that dystroglycan is an essential synaptic organizer at GABAergic synapses in Purkinje cells.

肌营养不良蛋白-糖蛋白复合物（DGC）将细胞内细胞骨架与细胞外基质联系起来。在神经元中，DGC的两个主要成分dystroglycan和dystrophin位于GABA能突触的子集，其功能尚不清楚。在这里，我们使用小鼠模型来分析DGC在抑制性突触的组织和功能中的特定作用。全长肌营养不良蛋白的丢失mdx小鼠从小脑浦肯野细胞的突触后抑制位点选择性清除跨膜β-dystroglycan同种型。值得注意的是，细胞外α-dystroglycan亚基，GABA _A受体和neuroligin 2的突触分布没有差异。相反，浦肯野细胞中dystroglycan基因的条件性缺失会导致DGC的破坏和突触后严重受损。神经胶蛋白2，GABA _A的聚集受体和支架蛋白。因此，全细胞膜片钳分析显示从浦肯野细胞记录的自发IPSC的频率和幅度显着降低。从长远来看，肌营养不良蛋白的缺失会导致Purkinje细胞的GABA能神经支配显着减少，并导致运动学习功能受损。这些结果表明，dystroglycan是Purkinje细胞中GABA能突触的重要突触组织者。