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

Na-Ryum Bin; Ke Ma; Hidekiyo Harada; Chi-Wei Tien; Fiona Bergin; Kyoko Sugita; Thomas T Luyben; Masahiro Narimatsu; Zhengping Jia; Jeffrey L Wrana; Philippe P Monnier; Liang Zhang; Kenichi Okamoto; Shuzo Sugita

doi:10.1016/j.celrep.2018.05.026

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

Cell Rep. 2018 Jun 5;23(10):2955-2966. doi: 10.1016/j.celrep.2018.05.026.

Authors

Na-Ryum Bin¹, Ke Ma², Hidekiyo Harada³, Chi-Wei Tien⁴, Fiona Bergin⁵, Kyoko Sugita³, Thomas T Luyben⁵, Masahiro Narimatsu⁶, Zhengping Jia⁷, Jeffrey L Wrana⁵, Philippe P Monnier⁸, Liang Zhang⁹, Kenichi Okamoto⁵, Shuzo Sugita¹⁰

Affiliations

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.

PMID: 29874582
DOI: 10.1016/j.celrep.2018.05.026

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CA1 Region, Hippocampal / physiology*
Cells, Cultured
Excitatory Postsynaptic Potentials / physiology
Gene Deletion
Long-Term Potentiation / physiology
Mice, Knockout
Neuronal Plasticity*
Neurons / physiology*
Organ Specificity
Qa-SNARE Proteins / metabolism*
Receptors, AMPA / metabolism
Receptors, Glutamate / metabolism
Receptors, N-Methyl-D-Aspartate / metabolism
Spatial Memory
Synapses / metabolism*
Synaptic Transmission*

Substances

Qa-SNARE Proteins
Receptors, AMPA
Receptors, Glutamate
Receptors, N-Methyl-D-Aspartate

Grants and funding

CIHR/Canada