This model is published in E.E. Saftenku "Modeling of slow glutamate diffusion and AMPA receptor activation in the cerebellar glomerulus", J. Theor. Biol, 2005, vol. 234, N 3,P. 363-382 (PMID 15784271). Synaptic conductances are influenced markedly by the geometry of the space surrounding the synapse since the transient glutamate concentration in the synaptic cleft is determined by this geometry. In our paper we attempted to understand the reasons for slow glutamate diffusion in the cerebellar glomerulus, a structure situated around the enlarged mossy fiber terminal in the cerebellum and surrounded by a glial sheath. For this purpose, analytical expressions for glutamate diffusion in the glomerulus were considered in the models with two-(2D), three- (3D), and fractional two-three dimensional (2D-3D) geometry with an absorbing boundary. The time course of average glutamate concentration in the synaptic cleft of the mossy fiber-granule cell connection was calculated for both direct release of glutamate from the synaptic unit, and for cumulative spillover of glutamate from neighboring release sites. Several kinetic schemes were examined, and the parameters of the diffusion models were estimated by identifying theoretical activation of AMPA receptors with direct release and spillover components of published experimental AMPA receptor-mediated EPSCs (DiGregorio, Nusser, Silver, 2002). We assumed that anomalous diffusion of glutamate occurs in the glomerulus. Our assumption was confirmed by a good fit and match of experimental estimations and theoretical parameters, obtained in the simulations that use an approximation of anomalous diffusion by a solution for fractional Brownian motion. Keywords: Glutamate diffusion, Cerebellar granule cells, Spillover. Simulations. Begin from mosinit.hoc. Clicking on buttons, you can choose the models with absorbing boundary, closed boundary or without boundary. For each model you can choose the simulation of glutamate diffusion in the environment with 2D, 3D or 2D-3D geometry and compute direct release and spillover components of AMPAR activation as in our Fig. 7. Only simple 3-state kinetic schemes of AMPARs with rate constants extracted from receptor kinetics during exposure of definite glutamate concentrations to outside-out patches from cultured granule cells are used in our examples. Clicking on button "Fractional Brownian motion" you can simulate anomalous glutamate diffusion in the model with absorbing boundary (Fig. 12a,b). Clicking on "Direct summation of glutamate", you can reproduce four possible combinations of direct release and spillover AMPAR-mediated EPSCs (Fig. 10). These EPSCs are evoked by two consecutive stimuli with time interval 10 ms and can be observed under assumption of 2 vesicles in the ready-release pool and the hypothesis of one vesicle release per AP. The density of active release sites is calculated in accordance with changes of release probability at each AP. If there is only one vesicle in the pool, then Markram and Tsodyks model for determination of release probability can be used. The use of the calculated release probability in the expression for ionic current will give incorrect result as such a kind of modeling assumes that AMPARs are desensitized to such an extent for the second AP as if all release sites had released vesicles on the first AP. In reality not more than P1*100% synaptic units can be desensitized by a direct release of glutamate, but synaptic units are desensitized to a lesser extent by spillover glutamate. All parameters of the model can be changed in the respective boxes. Changelog --------- 2022-05: Updated MOD files to contain valid C++ and be compatible with the upcoming versions 8.2 and 9.0 of NEURON.