Combined Effects of Feedforward Inhibition and Excitation in Thalamocortical Circuit on the Transitions of Epileptic Seizures.

Denggui Fan,Qian Wang,Lixia Duan,Guoming Luan

doi:10.3389/fncom.2017.00059

Abstract

The mechanisms underlying electrophysiologically observed two-way transitions between absence and tonic-clonic epileptic seizures in cerebral cortex remain unknown. The interplay within thalamocortical network is believed to give rise to these epileptic multiple modes of activity and transitions between them. In particular, it is thought that in some areas of cortex there exists feedforward inhibition from specific relay nucleus of thalamus (TC) to inhibitory neuronal population (IN) which has even more stronger functions on cortical activities than the known feedforward excitation from TC to excitatory neuronal population (EX). Inspired by this, we proposed a modified computational model by introducing feedforward inhibitory connectivity within thalamocortical circuit, to systematically investigate the combined effects of feedforward inhibition and excitation on transitions of epileptic seizures. We first found that the feedforward excitation can induce the transition from tonic oscillation to spike and wave discharges (SWD) in cortex, i.e., the epileptic tonic-absence seizures, with the fixed weak feedforward inhibition. Thereinto, the phase of absence seizures corresponding to strong feedforward excitation can be further transformed into the clonic oscillations with the increasing of feedforward inhibition, representing the epileptic absence-clonic seizures. We also observed the other fascinating dynamical states, such as periodic 2/3/4-spike and wave discharges, reversed SWD and clonic oscillations, as well as saturated firings. More importantly, we can identify the stable parameter regions representing the tonic-clonic oscillations and SWD discharges of epileptic seizures on the 2-D plane composed of feedforward inhibition and excitation, where the physiologically plausible transition pathways between tonic-clonic and absence seizures can be figured out. These results indicate the functional role of feedforward pathways in controlling epileptic seizures and the modified thalamocortical model may provide a guide for future efforts to mechanistically link feedforward pathways in the pathogenesis of epileptic seizures.

Highlights

Epilepsy is a debilitating condition of chronic neurological unprovoked seizures (Kramer et al, 2005; Vaurio et al, 2017), which can induce the cognitive, linguistic and behavioral disorders (Barnes and Paolicchi, 2008; Caplan et al, 2008), extending well beyond the immediate effect from seizures (Vaurio et al, 2017)
In this paper, using a modified thalamocortical neural field model network, we systematically investigated the combined effects of feedforward inhibition and excitation from thalamus to cortex on the epileptic seizure transitions
Electrophysiological experiments have long revealed the existence of two-way transitions between absence and tonic-clonic epileptic seizures in the cerebral cortex (Mayville et al, 2000; Shih and Hirsch, 2003)

Summary

Introduction

Epilepsy is a debilitating condition of chronic neurological unprovoked seizures (Kramer et al, 2005; Vaurio et al, 2017), which can induce the cognitive, linguistic and behavioral disorders (Barnes and Paolicchi, 2008; Caplan et al, 2008), extending well beyond the immediate effect from seizures (Vaurio et al, 2017). Experimental and computational evidences have suggested that these seizures are closely related to each other (Devinsky et al, 1988; Rogers et al, 2012; Varon Perez et al, 2012; Fan et al, 2015; Li et al, 2016a,b; Liu et al, 2016). This could be attributable to concomitance of multiple intricate mechanisms. Extensive observations and research have elucidated the mechanisms underlying the absence and tonic-clonic seizures, how these two seizures transit from each other remains an unanswered question in epileptology

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Conclusion