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.
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.
2022-05: Updated MOD files to contain valid C++ and be compatible
with the upcoming versions 8.2 and 9.0 of NEURON.