Stochastic fluctuations of the quantal EPSC amplitude in computer simulated excitatory synapses of hippocampus

The postsynaptic response in glutamatergic synapses of hippocampus, produced by the release of a single presynaptic vesicle, shows a large variability in amplitude not only among the synapses, but also for a single synapse. A mathematical modelling based on a Brownian motion for the diffusion of glutamate molecules and receptor binding was applied to study the possible sources of the quantal variability. Detailed, geometric and functional, descriptions of the vesicle, of the fusion pore and of the synaptic cleft were used and quantal (or miniature) EPSCs were computed. Our results show non-saturation of AMPA receptors, attributable to the small number of molecules contained in the glutamate vesicles of hippocampus. NMDA receptor saturation was obtained rarely, only in very specific instances. We concluded that the lack of AMPA saturation and intrinsic random variations in basic presynaptic elements, such as the vesicle volume and the vesicle docking position, are the main causes of the observed stochastic variability of the quantal EPSC amplitude. Only minor effects can be ascribed to postsynaptic sources.