Spontaneous Oscillations of Dressed Neurons: A New Mechanism for Epilepsy?

Abstract

Most modeling studies of neurons and neuronal networks are based on the assumption that the neurons are isolated from their normal environment. Based on recent experimental data we put forward a model for neurons that incorporates the influence of the surrounding glia (dressed neurons). We predict seizurelike spontaneous oscillations in the absence of stimuli for strong coupling between neurons and astrocytes. Consistent with our predictions, a signature of this enhanced crosstalk, over expression of glutamate receptors in astrocytes, has been observed specifically in epileptic tissue.

Dynamics of a minimal neural model consisting of an astrocyte, a neuron, and an interneuron

“…These results are in disagreement with those of Nadkarni and Jung [51,52] that instead predict an indefinite firing of the pyramidal neuron for suitable r PY values. These contrasting results can be accounted for by the different calcium membrane fluxes between the two models.…”

“…where H(x) is the Heaviside function; A astro = 2.11 μA/cm 2 ; [Ca 2+ ] i is the cytosolic calcium concentration in the astrocyte in nanomolar units [51,52]. Concerning the interneuron, the corresponding depolarization current is of the same form as Eq.…”

“…These contrasting results can be accounted for by the different calcium membrane fluxes between the two models. In fact, additional simulations performed with our model have shown that a reduction of the value of the constant k 5 (for instance, k 5 = 0.15 s −1 ) describing the calcium extrusion rate from the cell leads to indefinite firing as predicted by Nadkarni and Jung [51,52] (data not shown).…”

“…The mechanisms regulating the ATP release from the astrocytes are not well known; thus, for simplicity, it will be assumed here that there is a fixed concentration of extracellular ATP that will be considered as a control parameter. The depolarization of the neuron and the interneuron arising from the release of glutamate from the astrocyte is described by using the model of Nadkarni and Jung [51,52], which is based on the experimental data of Parpura and Haydon [8]. As discussed previously, the elevation of the intracellular calcium level in astrocytes triggers the release of glutamate from these cells leading to a modulation of the neural activity [4,5,8,11,12,20,42].…”

“…To describe the production of IP 3 in the astrocyte triggered by the discharge of the excitatory cell, the simple mathematical model used by Nadkarni and Jung [51,52] is adopted here. Let r PY be the rate of production of IP 3 when an action potential is generated by the pyramidal cell and V Th = −50 mV be a membrane potential threshold value.…”