Figure 1.  Glial cell networks modulate excitation-inhibition balance during epileptic seizures. A, A model of connected excitatory and inhibitory neuronal populations shows high amplitude oscillations when GABAergic inhibition is reduced (simulating the effect of PTZ treatment). This simulated seizure activity represents coordinated oscillations of excitatory and inhibitory populations, which when plotted against each other form so-called limit cycles. The value of GABAergic inhibition at which stationary activity transitions into the high amplitude limit cycle is known as bifurcation point. B, Here a syncytial network of glial cells is added to the model above with other parameters unchanged. The syncytium allows for lateral spread of activity and is recurrently coupled to excitatory cells, reproducing calcium mediated glial glutamate release. Without changing neuronal parameters from (A), the glial cells alter the response of the whole system. Specifically, much smaller reductions of GABAergic inhibition are sufficient to push the system into the high-amplitude, limit-cycle regime. Glial cells can therefore contribute to the emergence of generalized seizure-like dynamics in simple network models of neuronal population activity. PTZ indicates pentylenetetrazole.