Transmitter Concentration Pro les in the Synaptic Cleft: An Analytical Model of Release and Di usion

A three-dimensional model for release and di usion of glutamate in the synaptic cleft was developed and solved analytically. The model consists of a source function describing transmitter release from the vesicle and a di usion function describing the spread of transmitter in the cleft. Concentration pro les of transmitter at the postsynaptic side were calculated for di erent transmitter concentrations in a vesicle, release scenarios and di usion coe cients. From the concentration pro les the receptor occupancy could be determined using AMPA receptor kinetics. It turned out that saturation of receptors and su ciently fast currents could only be obtained if the di usion coe cient was one order of magnitude lower than generally assumed, and if the postsynaptic receptors formed clusters with a diameter of roughly 100 nm directly opposite the release sites. Under these circumstances the gradient of the transmitter concentration at the postsynaptic membrane outside the receptor clusters was steep with minimal crosstalk among neighboring receptor clusters. These ndings suggest, that to each release site a corresponding receptor aggregate exists, subdividing an individual synapse into independent functional subunits without the need for speci c lateral di usion barriers.