Balance of synaptic and electrotonic connections controls the excitability of networks in biophysical model of epilepsy

Abstract

Recent studies have implicated astrocytes in multiple active roles in neuronal networks. In particular they have been shown to be able to moderate and alter neural firing patterns both in normal and epileptic conditions. In addition, it has been proposed that one of the roles of gap junctions between astrocytes, as well as neurons is in increasing synchronization of neuronal firing and potential epileptogenic effect. In this study we build upon a model of a network that incorporates both pyramidal cells and interneurons as well as astrocytes with potassium clearance mechanisms and basic calcium dynamics. We include electrotonic connections between cells to be able to separate the effects of synaptic connections and gap junctions on neuronal hyperexcitability. Preliminary findings of this model show that under normal conditions, when gap junctions are blocked the network exists in an interictal-like state. When the system is put in a zero calcium environment (i.e. synaptic connections are disabled), the network enters spontaneous rhythmic bursting with very regular spiking. This suggests that electrotonic connections play a crucial role in the epileptogenesis within the neuronal network.

Low-to-High Cross-Frequency Coupling in the Electrical Rhythms as Biomarker for Hyperexcitable Neuroglial Networks of the Brain

“…Finally, although in this model we included some gap junctions between pyramidal cells and interneurons, many more exist between many cells in the brain, including interneurons, pyramidal cells, and astrocytes, which can have varying effect on both potassium concentrations and epileptogenesis [47]. Our preliminary results on effects of gap junctions in neuro-glial networks have shown that astrocytic gap junctions could help to ameliorate seizure-like states [48], possibly due to increased potassium clearance. Including a more diverse selection of gap junctions in the model could help model the additional role of astrocytes in maintaining excitability balance in neuro-glial networks.…”