Division of Fundamental Neurobiology, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Division of Fundamental Neurobiology, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada; Department of Pediatrics, The First Hospital of Jilin University School of Medicine, Changchun, Jilin 130021, China.
Cell Rep. 2018 Jun 5;23(10):2955-2966. doi: 10.1016/j.celrep.2018.05.026.
Trafficking of neurotransmitter receptors on postsynaptic membranes is critical for basal neurotransmission and synaptic plasticity, yet the underlying mechanisms remain elusive. Here, we investigated the role of syntaxin 4 in postsynaptic hippocampal CA1 neurons by analyzing conditional knockout (syntaxin 4 cKO) mice. We show that syntaxin 4 cKO resulted in reduction of basal neurotransmission without changes in paired-pulse ratios. Both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA) receptor-mediated charge transfers were diminished. Patch-clamp experiments revealed that amplitudes, but not frequencies, of spontaneous excitatory postsynaptic currents are reduced. Syntaxin 4 knockout (KO) caused drastic reduction in expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA) receptors in cultured hippocampal neurons. Furthermore, cKO caused defects in theta-burst stimulation induced long-term potentiation and spatial learning as assessed by a water maze task, indicating that synaptic plasticity was altered. Our data reveal a crucial role of syntaxin 4 in trafficking of ionotropic glutamate receptors that are essential for basal neurotransmission, synaptic plasticity, and spatial memory.
突触后膜神经递质受体的转运对于基础神经传递和突触可塑性至关重要，但潜在的机制仍难以捉摸。在这里，我们通过分析条件敲除（syntaxin 4 cKO）小鼠研究了 syntaxin 4 在海马 CA1 神经元突触后的作用。我们发现 syntaxin 4 cKO 导致基础神经传递减少，而不会改变成对脉冲比。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和 N-甲基-D-天冬氨酸（NMDA）受体介导的电荷转移都减少了。膜片钳实验显示，自发性兴奋性突触后电流的幅度而不是频率降低。突触小泡蛋白 4 敲除（KO）导致培养的海马神经元表面 AMPA 和 NMDA 受体的表达明显减少。此外，cKO 导致 theta 爆发刺激诱导的长时程增强和空间学习的缺陷，如通过水迷宫任务评估，表明突触可塑性发生改变。我们的数据揭示了 syntaxin 4 在离子型谷氨酸受体转运中的关键作用，这些受体对于基础神经传递、突触可塑性和空间记忆至关重要。
