title: Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP.
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 Ca2+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.
authors.affiliation: Department of Molecular &Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305, USA.|Nancy Pritzker Laboratory, Stanford University Medical School, Stanford, California 94305, USA.|Department of Psychiatry &Behavioral Sciences, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Dick
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Molecular &Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Taulant
authors.initials: T
authors.lastname: Bacaj
authors.affiliation: Nancy Pritzker Laboratory, Stanford University Medical School, Stanford, California 94305, USA.|Department of Psychiatry &Behavioral Sciences, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Wade
authors.initials: W
authors.lastname: Morishita
authors.affiliation: Nancy Pritzker Laboratory, Stanford University Medical School, Stanford, California 94305, USA.|Department of Psychiatry &Behavioral Sciences, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Goswami
authors.affiliation: Department of Neurosurgery, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Arendt
authors.affiliation: Department of Molecular &Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Nancy Pritzker Laboratory, Stanford University Medical School, Stanford, California 94305, USA.|Department of Psychiatry &Behavioral Sciences, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
authors.affiliation: Department of Molecular &Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis; D005260:Female; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D009154:Mutation; D021381:Protein Transport; D017966:Pyramidal Cells / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D050857:Synaptotagmins; D002118:Calcium