Functional modeling of astrocytes in epilepsy: a feedback system perspective

Abstract

Astrocytes, a subtype of glial cells, in the brain provide structural and metabolic supports to the nervous system. They are also active partners in synaptic transmission and neuronal activities. In the present study, a biologically plausible thalamocortical neural population model (TCM) originally proposed by Suffczynski et al. (Neuroscience 126(2):467–484, 2004) is extended by integrating the functional role of astrocytes in the regulation of synaptic transmission. Therefore, the original TCM is modified to consider neuron-astrocyte interactions. Using the modified model, it is demonstrated that the healthy astrocytes are capable to compensate the variation of cortical excitatory input by increasing their firing frequency. In this way, they can preserve the attractor corresponding to the normal activity. Furthermore, the performance of the pathological astrocytes is also investigated. It is hypothesized that one of the plausible causes of seizures is the malfunction of astrocytes in the regulatory feedback loop. That is, pathologic astrocytes are not any more able to regulate and/or compensate the excessive increase of the cortical input. Therefore, pathologic astrocytes lead to the emergence of paroxysmal attractor. Results demonstrate that disruption of the homeostatic or signaling function of astrocytes can initiate the synchronous firing of neurons, suggesting that astrocytes might be one of the potential targets for the treatment of epilepsy.