Stochastic fluctuations of the synaptic function.

The peak amplitudes of the quantal Excitatory Post Synaptic Currents in single hippocampal synapses show a large variability. Here, we present the results of a mathematical, computational investigation on the main sources of this variability. A detailed description of the synaptic cleft, rigorously based on empirically-derived parameters, was used. By using a Brownian motion model of neurotransmitter molecule diffusion, quantal EPSCs were computed by a simple kinetic schema of AMPA receptor dynamics. Our results show that the lack of saturation of AMPA receptors obtained in these conditions, combined with stochastic variations in basic presynaptic elements, such as the vesicle volume, the vesicle docking position, and the vesicle neurotransmitter concentration can explain almost the entire range of EPSC variability experimentally observed.