Role of chloride concentration in modulating seizure transitions in excitatory and inhibitory networks

TL;DR

This study models how chloride homeostasis influences seizure stages and transitions in neural networks, revealing key parameters that control seizure dynamics and their sensitivity to inhibition.

Contribution

It introduces a conductance-based network model demonstrating chloride's role in organizing seizure stages and transitions, highlighting the impact of synaptic conductance fractions.

Findings

Decreasing chloride influx fraction shortens seizures and prevents initiation.

High influx fraction promotes tonic and clonic seizure stages and spiral-wave dynamics.

Recurrent excitation and inhibition modulate seizure duration and stage emergence.

Abstract

Experimental evidence indicates that intracellular chloride concentration regulates the excitation and inhibition (EI) balance, yet the mechanisms by which activity-dependent chloride dynamics drive seizure evolution and stage transitions remain unclear. We present a conductance-based neuronal network in which EI balance emerges from chloride homeostasis via channel-mediated influx and transporter-mediated extrusion. We show that the fraction of inhibitory synaptic conductance contributing to channel-mediated influx acts as a control parameter that organizes seizure dynamics into distinct stages,pre-ictal, ictal-tonic, and ictal-clonic,distinguished by characteristic amplitude and frequency signatures. Decreasing this fraction shortens ictal activity and suppresses seizure initiation, whereas high fraction promotes the emergence of ictal-tonic and ictal-clonic stages and spiral-wave dynamics, rendering seizure dynamics largely insensitive to inhibition. At intermediate values, seizures bypass the ictal-tonic stage and emerge directly as the icta,clonic stage. Moreover, joint variation of fractions with synaptic strengths reveals that recurrent excitation expands the tonic-clonic seizure, while recurrent inhibition prolongs pre-ictal states and suppresses ictal-clonic activity.