Multivesicular release at Schaffer collateral-CA1 hippocampal synapses

Whether an individual synapse releases single or multiple vesicles of transmitter per action potential is contentious and probably depends on the type of synapse. One possibility is that multivesicular release (MVR) is determined by the instantaneous release probability (P_r) and therefore can be controlled by activity-dependent changes in P_r. We investigated transmitter release across a range of P_r at synapses between Schaffer collaterals (SCs) and CA1 pyramidal cells in acute hippocampal slices using patch-clamp recordings. The size of the synaptic glutamate transient was estimated by the degree of inhibition of AMPA receptor EPSCs with the rapidly equilibrating antagonist γ-D-glutamylglycine. The glutamate transient sensed by AMPA receptors depended on P_r but not spillover, indicating that multiple vesicles are essentially simultaneously released from the same presynaptic active zone. Consistent with an enhanced glutamate transient, increasing P_r prolonged NMDA receptor EPSCs when glutamate transporters were inhibited. We suggest that MVR occurs at SC-CA1 synapses when P_r is elevated by facilitation and that MVR maybe a phenomenon common to many synapses throughout the CNS.