Transmitter concentration profiles in the synaptic cleft: an analytical model of release and diffusion

A three-dimensional model for release and diffusion 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 diffusion function describing the spread of transmitter in the cleft. Concentration profiles of transmitter at the postsynaptic side were calculated for different transmitter concentrations in a vesicle, release scenarios, and diffusion coefficients. From the concentration profiles the receptor occupancy could be determined using alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor kinetics. It turned out that saturation of receptors and sufficiently fast currents could only be obtained if the diffusion coefficient 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 cross-talk among neighboring receptor clusters. These findings suggest that for each release site a corresponding receptor aggregate exists, subdividing an individual synapse into independent functional subunits without the need for specific lateral diffusion barriers.