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 th e synaptic cleft was developed and solved analytically. The model cons ists of a source function describing transmitter release from the vesi cle and a diffusion function describing the spread of transmitter in t he cleft. Concentration profiles of transmitter at the postsynaptic si de were calculated for different transmitter concentrations in a vesic le, release scenarios, and diffusion coefficients. From the concentrat ion profiles the receptor occupancy could be determined using lpha-ami no-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 recept ors formed clusters with a diameter of roughly 100 nm directly opposit e the release sites. Under these circumstances the gradient of the tra nsmitter concentration at the postsynaptic membrane outside the recept or clusters was steep, with minimal cross-talk among neighboring recep tor clusters. These findings suggest that for each release site a corr esponding receptor aggregate exists, subdividing an individual synapse into independent functional subunits without the need for specific la teral diffusion barriers.