Abstract
The gliotransmitter glutamate released from astrocytes can modulate neuronal firing by activating neuronal N-methyl-D-aspartic acid (NMDA) receptors. This enables astrocytic glutamate(AG) to be involved in neuronal physiological and pathological functions. Based on empirical results and classical neuron-glial “tripartite synapse” model, we propose a practical model to describe extracellular AG oscillation, in which the fluctuation of AG depends on the threshold of calcium concentration, and the effect of AG degradation is considered as well. We predict the seizure-like discharges under the dysfunction of AG degradation duration. Consistent with our prediction, the suppression of AG uptake by astrocytic transporters, which operates by modulating the AG degradation process, can account for the emergence of epilepsy.
Highlights
The gliotransmitter glutamate released from astrocytes can modulate neuronal firing by activating neuronal N-methyl-D-aspartic acid (NMDA) receptors
With higher level of equilibrium concentrations, such as 0.5 μM and 0.7 μM, a seizure-like discharges are present in the soma, as it can be observed in Fig. 1(d,e) respectively. Both the “depolarization block” (DB) discharge and the “refractory status epilepticus”(RSE)-like discharge are present in the time series of neuronal discharge
Tian et al in experiments have reported that the accumulation of astrocytic glutamate (AG) has been a major source of neuronal epilepsy[29,30,31], AG uptake by astrocytic transporters in some experimental results was shown to be an efficient pathway to protect neurons from epilepsies[33,34]
Summary
The reduced “tripartite synapse” is a three-compartment model of a somatic neuron, a dendrite and the neighboring astrocyte developed by Nardkarni and Jung[44]. In this model, a somatic neuron transfers its firing to the dendrite through electrical coupling. To model of the pyramidal cell and the dendrite, the well-known Pinsky-Rinzel (PR) model[52] has been used in the classical “tripartite synapse” model. This model can well describe the main features of Na+ and K+ ion conductance of the soma and the calcium dependence of the dendrite. The action potentials of the soma (Vs) and the dendrite (Vd) are described by the following set of equations: Cm dV dt s
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