Modified thalamocortical model: A step towards more understanding of the functional contribution of astrocytes to epilepsy

It is evident that the cortex plays a primary role in seizure generation. At the same time, various experimental results clearly confirm that thalamic neurons are also actively involved in seizure generation and spreading. On the other hand, recent neurophysiologic findings suggest that astrocytes regulate dynamically the synaptic activity in neuronal networks. Therefore, in the present study, the thalamocortical neural population model (TCPM) is modified by embedding into the model the functional role of astrocytes in the regulation of synaptic transmission. Using the modified TCPM (MTCPM) we examined the hypothesis that one of the possible causes of neural hypersynchronization is the dysfunction of astrocytes in the regulatory feedback loop. Then, two MTCPMs are coupled via excitatory synapses and the astrocytes are also coupled together through gap junctions. Utilizing the MTCPM and CMTCPM, the transition from normal to malfunctioned states is analyzed using a dynamical system approach. In this way, the hypothesis is investigated and it is demonstrated that the healthy astrocytes provide feedback control to regulate neural activity. That is, the astrocytes compensate to a large extent variations in the coupling between neural populations and maintain the balance between the excitation and inhibition levels. However, the malfunctioned astrocytes are no longer able to regulate and/or compensate the excessive increase of the inter-population coupling strength. As a consequence, disruption of the signaling function of astrocytes could contribute to the neuronal hyperexcitability and generating epileptiform activity. These results suggest that astrocytes might be one of the potential targets for the treatment of epilepsy.