Crucial Role of Postsynaptic Syntaxin 4 in Mediating Basal Neurotransmission and Synaptic Plasticity in Hippocampal CA1 Neurons.
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.
['Bin|Na-Ryum|NR|', 'Ma|Ke|K|', 'Harada|Hidekiyo|H|', 'Tien|Chi-Wei|CW|', 'Bergin|Fiona|F|', 'Sugita|Kyoko|K|', 'Luyben|Thomas T|TT|', 'Narimatsu|Masahiro|M|', 'Jia|Zhengping|Z|', 'Wrana|Jeffrey L|JL|', 'Monnier|Philippe P|PP|', 'Zhang|Liang|L|', 'Okamoto|Kenichi|K|', 'Sugita|Shuzo|S|']
D000818:Animals D056547:CA1 Region, Hippocampal D002478:Cells, Cultured D019706:Excitatory Postsynaptic Potentials D017353:Gene Deletion D017774:Long-Term Potentiation D018345:Mice, Knockout D009473:Neuronal Plasticity D009474:Neurons D009928:Organ Specificity D050765:Qa-SNARE Proteins D018091:Receptors, AMPA D017470:Receptors, Glutamate D016194:Receptors, N-Methyl-D-Aspartate D065852:Spatial Memory D013569:Synapses D009435:Synaptic Transmission
syntaxin 4 basal neurotransmission CA1 AMPA receptors LTP NMDA receptors hippocampus learning and memory postsynaptic dendritic spines receptor trafficking