Crucial Role of Postsynaptic Syntaxin 4 in Mediating Basal Neurotransmission and Synaptic Plasticity in Hippocampal CA1 Neurons
Open accessAbstract
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.
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Blocking postsynaptic exocytosis by a variety of means blocks LTP/sLTP.
“Numerous studies have shown that blocking postsynaptic exocytosis by a variety of means blocks LTP/sLTP (195, 249, 250, 332–338).”
From Synaptic memory and CaMKII (2023) · cites this paper as [336]
Stx-4 is reported to be required for LTP.
“while on the other hand Stx-4 is reported to be required for LTP (336, 338).”
From Synaptic memory and CaMKII (2023) · cites this paper as [336]
Cites
NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders
Lau, C. G., & Zukin, R. S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2153 · Cited by 1,159 · see citing works
Postsynaptic Complexin Controls AMPA Receptor Exocytosis during LTP
Ahmad, M., Polepalli, J. S., Goswami, D., Yang, X., Kaeser-Woo, Y. J., Südhof, T. C., & Malenka, R. C. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.020 · Cited by 133 · see citing works
SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking
Lau, C. G., Takayasu, Y., Rodenas-Ruano, A., Paternain, A. V., Lerma, J., Bennett, M. V. L., & Zukin, R. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4933-08.2010 · Cited by 120 · see citing works
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Regulation of NMDA glutamate receptor functions by the GluN2 subunits
Vieira, M., Yong, X. L. H., Roche, K. W., & Anggono, V. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14970 · Cited by 151 · see citing works
“For synapse maturation to occur, concomitant insertion of AMPARs (Leinekugel, Medina, Khalilov, Ben-Ari, & Khazipov, 1997) and a switch in NMDAR subunit composition from GluN2B to GluN2A are necessary (Barria & Malinow, 2002).”
BackgroundInfluentialNicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“339), while on the other hand Stx-4 is reported to be required for LTP (336, 338).”
Background
- Authors
- Bin, N.-R., Ma, K., Harada, H., Tien, C.-W., Bergin, F., Sugita, K., Luyben, T. T., Narimatsu, M., Jia, Z., Wrana, J. L., Monnier, P. P., Zhang, L., Okamoto, K., & Sugita, S.
- Affiliations
- University Health Network (CA)
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- Corresponding author
- Sugita, Shuzo
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 23
- Issue
- 10
- Pages
- 2955-2966
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2807670180
- Cited by
- 25
- References
- 3
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 2 · 2018: 4
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-06438)
- Heart and Stroke Foundation of Canada (0171)
- Canadian Institutes of Health Research (MOP-93665, 130573, CGS-D2)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- syntaxin 4, ionotropic glutamate receptors, AMPA receptors, NMDA receptor, synaptic plasticity, long-term potentiation, theta burst stimulation, spontaneous excitatory postsynaptic currents, spatial learning, CA1 pyramidal neurons, conditional knockout mice
- MeSH terms
- Animals, Cells, Cultured, Synaptic Transmission, Neuronal Plasticity, Neurons, Organ Specificity, Synapses, Receptors, N-Methyl-D-Aspartate, Gene Deletion, Receptors, Glutamate, Long-Term Potentiation, Receptors, AMPA, Mice, Knockout, Excitatory Postsynaptic Potentials, Qa-SNARE Proteins, CA1 Region, Hippocampal, Spatial Memory
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