Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP

Dick Wu, Taulant Bacaj, Wade Morishita, Debanjan Goswami, Kristin L. Arendt, Wei Xu, Lu Chen, Robert C. Malenka, Thomas C. Südhof

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69 Scopus citations

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, Ca2+ 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 Ca2+ -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 Ca2+ -dependent presynaptic vesicle exocytosis, also blocked Ca2+ -dependent postsynaptic AMPA receptor exocytosis, thereby abolishing LTP. Our results suggest that postsynaptic Syt1 and Syt7 act as redundant Ca2+ -sensors for Ca2+ -dependent exocytosis of AMPA receptors during LTP, and thereby delineate a simple mechanism for the recruitment of AMPA receptors that mediates LTP.

Original languageEnglish (US)
Pages (from-to)316-321
Number of pages6
JournalNature
Volume544
Issue number7650
DOIs
StatePublished - Apr 20 2017

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    Wu, D., Bacaj, T., Morishita, W., Goswami, D., Arendt, K. L., Xu, W., Chen, L., Malenka, R. C., & Südhof, T. C. (2017). Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP. Nature, 544(7650), 316-321. https://doi.org/10.1038/nature21720