Determinants of slowed diffusion in the complex space of the cerebellar glomerulus

Using analytical solutions for two- and three-dimensional (2D and 3D, respectively) and fractal 2D/3D geometry with an absorbing boundary, we modeled glutamate diffusion in a glomerulus, the structure situated around the mossy fiber (MF) terminal in the cerebellum and surrounded by a glial sheath. The model with fractal geometry gave the best fit of experimental AMPA and NMDA receptor-mediated evoked postsynaptic currents (EPSC) at the MF-granule cell synapse. A comparison of the numerically integrated glutamate concentration in an idealized model of glomerulus morphology with analytical solutions reveals that the peculiarities of glomerulus geometry can explain the better fit by the solution with fractal dimension only of experimental EPSC arising from local release, but not from spillover of glutamate. An asynchronous vesicle release only slightly influences the shape of the spillover waveform. Anomalously slow diffusion of glutamate can be an explanation of the observed discrepancy between experimental results and simulations with the 3D model. A good fit of spillover-induced EPSC obtained in the simulations that use a solution for fractional Brownian motion and a match of experimental estimations and theoretical parameters of the diffusion model confirms this assumption.