Synaptic inhibition and pathologic hyperexcitability through enhanced neuron-astrocyte interaction: a modeling study.

Recently, upregulation of metabotropic glutamate receptors (mGluRs) on hippocampal astrocytes in epileptic tissues has become part of the etiology of epilepsy and suggests the involvement of astrocytes in the disease. Through computational modeling, we have shown in previous work that upregulated mGluRs on astrocytes can give rise to positive feedback in closed loop neuron-astrocyte circuits with epilepsy-type spontaneous neuronal spiking. In this paper we further quantify the necessary degree of upregulation of astrocytic mGluRs, relate it to recent clinical and experimental studies, and address through computational modeling the role of synaptic inhibition through interneurons in this form of hyperexcitability. We conclude that inhibitive circuitry cannot tame this form of hyperexcitability.