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Postsynaptic Complexin Controls AMPA Receptor Exocytosis during LTP
Open accessAbstract
Long-term potentiation (LTP) is a compelling synaptic correlate of learning and memory. LTP induction requires NMDA receptor (NMDAR) activation, which triggers SNARE-dependent exocytosis of AMPA receptors (AMPARs). However, the molecular mechanisms mediating AMPAR exocytosis induced by NMDAR activation remain largely unknown. Here, we show that complexin, a protein that regulates neurotransmitter release via binding to SNARE complexes, is essential for AMPAR exocytosis during LTP but not for the constitutive AMPAR exocytosis that maintains basal synaptic strength. The regulated postsynaptic AMPAR exocytosis during LTP requires binding of complexin to SNARE complexes. In hippocampal neurons, presynaptic complexin acts together with synaptotagmin-1 to mediate neurotransmitter release. However, postsynaptic synaptotagmin-1 is not required for complexin-dependent AMPAR exocytosis during LTP. These results suggest a complexin-dependent molecular mechanism for regulating AMPAR delivery to synapses, a mechanism that is surprisingly similar to presynaptic exocytosis but controlled by regulators other than synaptotagmin-1.
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“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 [333]
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Metadata
- Authors
- Ahmad, M., Polepalli, J. S., Goswami, D., Yang, X., Kaeser-Woo, Y. J., Südhof, T. C., & Malenka, R. C.
- Affiliations
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Malenka, Robert C.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 73
- Issue
- 2
- Pages
- 260-267
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3269030
- OpenAlex
- W2085433160
- Cited by
- 133
- References
- 51
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 15 · 2017: 11 · 2016: 12 · 2015: 18 · 2014: 10 · 2013: 13 · 2012: 3
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH06334, R01MH063394, P50MH086403, P50 MH0864)
- 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
- complexin, long-term potentiation, SNARE complex, NMDA receptor activation, synaptotagmin-1, hippocampal neurons, neurotransmitter release regulation
- MeSH terms
- Animals, Exocytosis, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Long-Term Potentiation, Receptors, AMPA, Excitatory Postsynaptic Potentials, Protein Transport, Adaptor Proteins, Vesicular Transport, SNARE Proteins, Synaptotagmin I, Mice, CA1 Region, Hippocampal, Post-Synaptic Density
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