  We develop a spatially explicit biophysical model of the hippocampal CA3-CA1
presynaptic bouton to study local calcium dynamics leading to vesicle fusion. A
kinetic model with two calcium sensors is formulated specifically for the
CA3-CA1 synapse. The model includes a sensor for fast synchronous release that
lasts a few tens of milliseconds and a sensor for slow asynchronous release
that lasts a few hundred milliseconds. We show that a variety of extant data on
CA3-CA1 synapse can be accounted for consistently only when a refractory period
of the order of few milliseconds between releases is introduced. Including a
second sensor for asynchronous release that has a slow unbinding site and
therefore an embedded long memory, is shown to play a role in short-term
plasticity by facilitating release. For synchronous release mediated by
Synaptotagmin II a third time scale is revealed in addition to the fast and
slow release. This third time scale corresponds to "stimulus-correlated
super-fast" neurotransmitter release. Our detailed spatial simulation indicates
that all three-time scales of neurotransmitter release are an emergent property
of the calcium sensor and independent of synaptic ultrastructure. Furthermore,
it allows us to identify features of synaptic transmission that are universal
and those that are modulated by structure.
