Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, 60590 Frankfurt am Main, Germany and.
Cereb Cortex. 2013 Nov;23(11):2700-11. doi: 10.1093/cercor/bhs260. Epub 2012 Aug 23.
Gephyrin is a scaffolding protein important for the postsynaptic clustering of inhibitory neurotransmitter receptors. Here, we investigated the properties of gephyrin scaffolds at γ-aminobutyric acid- (GABA-)ergic synapses in organotypic entorhino-hippocampal cultures prepared from a transgenic mouse line, which expresses green fluorescent protein-tagged gephyrin under the control of the Thy1.2 promoter. Fluorescence recovery after photobleaching revealed a developmental stabilization of postsynaptic gephyrin clusters concomitant with an increase in cluster size and synaptic strength between 1 and 4 weeks in vitro. Prolonged treatment of the slice cultures with diazepam or a GABAA receptor antagonist disclosed a homeostatic regulation of both inhibitory synaptic strength and gephyrin cluster size and stability in 4-weeks-old cultures, whereas at 1 week in vitro, the same drug treatments modulated GABAergic postsynapse and gephyrin cluster properties following a Hebbian mode of synaptic plasticity. Our data are consistent with a model in which the postnatal maturation of the hippocampal network endows CA1 pyramidal neurons with the ability to homeostatically adjust the strength of their inhibitory postsynapses to afferent GABAergic drive by regulating gephyrin scaffold properties.
网格蛋白是一种支架蛋白，对于抑制性神经递质受体的突触后聚集非常重要。在这里，我们研究了来自转基因小鼠系的器官型内嗅-海马培养物中 GABA 能突触处网格蛋白支架的特性，该小鼠系在 Thy1.2 启动子的控制下表达绿色荧光蛋白标记的网格蛋白。光漂白后荧光恢复显示，突触后网格蛋白簇在体外 1 至 4 周之间伴随着大小和突触强度的增加而发生发育稳定性。长时间用地西泮或 GABA A 受体拮抗剂处理切片培养物，揭示了在 4 周龄培养物中，两种抑制性突触强度和网格蛋白簇大小和稳定性的同源调节，而在体外 1 周时，相同的药物处理根据突触可塑性的赫布模式调节 GABA 能突触后和网格蛋白簇特性。我们的数据与以下模型一致，即海马网络的出生后成熟赋予 CA1 锥体神经元通过调节网格蛋白支架特性来对传入 GABA 能驱动进行同源性调节抑制性突触后强度的能力。
