Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP

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. Postsynaptic synaptotagmin-1 and synaptotagmin-7 mediate calcium-dependent exocytosis of AMPA receptors during long-term potentiation. Postsynaptic mediation of AMPA exocytosis Long-term potentiation (LTP) enables learning and memory through an increase of postsynaptic AMPA receptors for the neurotransmitter glutamate, but how these receptors are delivered to synapses in response to neuronal activity has been unclear. Now Thomas Sudhof and colleagues show that calcium-dependent exocytosis of postsynaptic AMPA receptors during LTP is redundantly mediated by the calcium sensors synaptotagmin-1 and synaptotagmin-7. The findings reveal an unexpected symmetry between the presynaptic and postsynaptic compartments in the mechanisms of vesicle trafficking.