A dynamics model of neuron-astrocyte network accounting for febrile seizures

Febrile seizure (FS) is a full-body convulsion caused by a high body temperature that affect young kids, however, how these most common of human seizures are generated by fever has not been known. One common observation is that cortical neurons become overexcited with abnormal running of sodium and potassium ions cross membrane in raised body temperature condition, Considering that astrocyte Kir4.1 channel play a critical role in maintaining extracellular homeostasis of ionic concentrations and electrochemical potentials of neurons by fast depletion of extracellular potassium ions, we examined here the potential role of temperature-dependent Kir4.1 channel in astrocytes in causing FS. We first built up a temperature-dependent computational model of the Kir4.1 channel in astrocytes and validated with experiments. We have then built up a neuron-astrocyte network and examine the role of the Kir4.1 channel in modulating neuronal firing dynamics as temperature increase. The numerical experiment demonstrated that the Kir4.1 channel function optimally in the body temperature around 37 °C in cleaning ‘excessive’ extracellular potassium ions during neuronal firing process, however, higher temperature deteriorates its cleaning function, while lower temperature slows down its cleaning efficiency. With the increase of temperature, neurons go through different stages of spiking dynamics from spontaneous slow oscillations, to tonic spiking, fast bursting oscillations, and eventually epileptic bursting. Thus, our study may provide a potential new mechanism that febrile seizures may be happened due to temperature-dependent functional disorders of Kir4.1 channel in astrocytes.