Glutamate diffusion and AMPA receptor activation in the cerebellar glomerulus (Saftenku 2005)

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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. Our paper is an attempt 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. ... Our results suggest at least a 7- to 10-fold lower apparent diffusion coefficient of glutamate in the porous medium of the glomerulus than in water. ... See paper for details and more.
1 . Saftenku EE (2005) Modeling of slow glutamate diffusion and AMPA receptor activation in the cerebellar glomerulus. J Theor Biol 234:363-82 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Extracellular;
Brain Region(s)/Organism:
Cell Type(s):
Gap Junctions:
Receptor(s): AMPA;
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s):
Implementer(s): Saftenku, Elena [esaft at];
Search NeuronDB for information about:  AMPA; Glutamate;
	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.

Saftenku EE (2005) Modeling of slow glutamate diffusion and AMPA receptor activation in the cerebellar glomerulus. J Theor Biol 234:363-82[PubMed]

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