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Cited by 195Neuroscience and Neuropharmacology ResearchCellular transport and secretionMemory and Neural Mechanisms

Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP

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Wu, Dick, Bacaj, Taulant, Morishita, Wade, Goswami, Debanjan, Arendt, Kristin L., Xu, Wei, Chen, Lu, Malenka, Robert C. +1 more·2017·Nature
DOI 10.1038/nature21720PMC PMC5734942
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Abstract

Strengthening of synaptic connections by NMDA (N-methyl-d-aspartate) receptor-dependent long-term potentiation (LTP) shapes neural circuits and mediates learning and memory. During the induction of NMDA-receptor-dependent LTP, Ca 2+ influx stimulates recruitment of synaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, thereby strengthening synapses. How Ca 2+ induces the recruitment of AMPA receptors remains unclear. Here we show that, in the pyramidal neurons of the hippocampal CA1 region in mice, blocking postsynaptic expression of both synaptotagmin-1 (Syt1) and synaptotagmin-7 (Syt7), but not of either alone, abolished LTP. LTP was restored by expression of wild-type Syt7 but not of a Ca 2+-binding-deficient mutant Syt7. Blocking postsynaptic expression of Syt1 and Syt7 did not impair basal synaptic transmission, reduce levels of synaptic or extrasynaptic AMPA receptors, or alter other AMPA receptor trafficking events. Moreover, expression of dominant-negative mutant Syt1 which inhibits Ca 2+-dependent presynaptic vesicle exocytosis, also blocked Ca 2+-dependent postsynaptic AMPA receptor exocytosis, thereby abolishing LTP. Our results suggest that postsynaptic Syt1 and Syt7 act as redundant Ca 2+-sensors for Ca 2+-dependent exocytosis of AMPA receptors during LTP, and thereby delineate a simple mechanism for the recruitment of AMPA receptors that mediates LTP.

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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 [195]

  • Postsynaptic Syt1/Syt7 are reported to be required for LTP.

    “Postsynaptic synaptotagin1 and 7 (Syt1/Syt7) have also been reported to be required for LTP (195).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [195]

  • AMPAR-containing vesicles are associated with synaptotagmin-1, which is involved in LTP.

    “Additional support for the vesicle-centric model is the finding that AMPAR-containing vesicles (obtained by immunoisolation) are associated with such proteins as synaptotagmin-1 (341), which is involved in LTP (195).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [195]

  • Voltage pulse potentiation (VPP) typically is transient, lasting no longer than 20 min.

    “the potentiation typically is transient, lasting no longer than 20 min (Refs. 189–193, but see Refs. 194, 195).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [195]

    The Methods section describes how voltage-pulse LTP was induced, and “Postsynaptic Syt1,7 loss blocks LTP” discusses its mechanism. Neither passage states that the potentiation is typically transient or lasts no longer than 20 minutes; searches for voltage-pulse LTP duration and decay found no such statement in our copy. (LLM, conf=0.73)

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Authors
Wu, D., Bacaj, T., Morishita, W., Goswami, D., Arendt, K. L., Xu, W., Chen, L., Malenka, R. C., & Südhof, T. C.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Stanford Medicine (US)
Corresponding author
  • Malenka, Robert C.
  • Südhof, Thomas C.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2017-03-29
Volume
544
Issue
7650
Pages
316-321
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature21720
PMC
PMC5734942
OpenAlex
W2600293296
Cited by
195
References
8
Citations by year
2026: 10 · 2025: 21 · 2024: 18 · 2023: 14 · 2022: 17 · 2021: 28 · 2020: 22 · 2019: 26 · 2018: 26 · 2017: 13
FWCI
11.65
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (K99MH107618, F32MH100752, R01MH091193, P50MH086403)
  • National Institute of Neurological Disorders and Stroke (R01NS077906)
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
synaptotagmin-1, synaptotagmin 7, long-term potentiation, calcium-dependent exocytosis, NMDA receptor, AMPA receptor trafficking, CA1 pyramidal neurons, vesicle trafficking
MeSH terms
Animals, Calcium, Exocytosis, Female, Male, Mutation, Synaptic Transmission, Synapses, Long-Term Potentiation, Pyramidal Cells, Receptors, AMPA, Protein Transport, Synaptotagmins, Mice, CA1 Region, Hippocampal

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