Role of chloride concentration in modulating seizure transitions in excitatory and inhibitory networks
Qianchen Gong, Yingpeng Liu, Yan Zhang, Muhua Zheng, Kesheng Xu
TLDR
This paper models how chloride concentration dynamics, specifically inhibitory synaptic conductance, control seizure initiation and progression through distinct stages.
Key contributions
- Modeled how chloride homeostasis regulates excitation-inhibition balance in neuronal networks.
- Identified a key inhibitory synaptic conductance fraction controlling seizure stage transitions.
- Demonstrated this fraction dictates seizure initiation, duration, and specific tonic/clonic stages.
- Showed recurrent excitation expands seizures, while inhibition prolongs pre-ictal states.
Why it matters
This paper clarifies how chloride dynamics drive seizure evolution and stage transitions, a critical but unclear mechanism. Identifying a key control parameter offers new insights into seizure initiation and progression, which could inform novel therapeutic strategies for epilepsy by targeting chloride homeostasis.
Original 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.
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