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Crucial Role of Postsynaptic Syntaxin 4 in Mediating Basal Neurotransmission and Synaptic Plasticity in Hippocampal CA1 Neurons.

Cell Rep. 2018 Jun 05;23(10):2955-2966
Na-Ryum Bin 1 , Ke Ma 2 , Hidekiyo Harada 3 , Chi-Wei Tien 4 , Fiona Bergin 5 , Kyoko Sugita 3 , Thomas T Luyben 5 , Masahiro Narimatsu 6 , Zhengping Jia 7 , Jeffrey L Wrana 5 , Philippe P Monnier 8 , Liang Zhang 9 , Kenichi Okamoto 5 , Shuzo Sugita 10
Na-Ryum Bin 1 , Ke Ma 2 , Hidekiyo Harada 3 , Chi-Wei Tien 4 , Fiona Bergin 5 , Kyoko Sugita 3 , Thomas T Luyben 5 , Masahiro Narimatsu 6 , Zhengping Jia 7 , Jeffrey L Wrana 5 , Philippe P Monnier 8 , Liang Zhang 9 , Kenichi Okamoto 5 , Shuzo Sugita 10
+ et al

[No authors listed]

Author information
  • 1 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.
  • 2 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.
  • 3 Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
  • 4 Division of Fundamental Neurobiology, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
  • 5 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • 6 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
  • 7 Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • 8 Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada; Department of Ophthalmology & Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • 9 Division of Fundamental Neurobiology, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada; Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • 10 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. Electronic address: ssugita@uhnres.utoronto.ca.

摘要


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.

KEYWORDS: AMPA receptors, CA1, LTP, NMDA receptors, basal neurotransmission, hippocampus, learning and memory, postsynaptic dendritic spines, receptor trafficking, syntaxin 4