The Influence of Sodium and Potassium Dynamics on Excitability, Seizures, and the Stability of Persistent States: II. Network and Glial Dynamics

TL;DR

This paper models how sodium and potassium dynamics in neurons, glia, and extracellular space influence excitability, seizure activity, and persistent states, highlighting glial roles in network stability and transient phenomena.

Contribution

It introduces a network model incorporating ionic dynamics and glial interactions to explain seizure-like activity and persistent state stability, advancing understanding of neural excitability mechanisms.

Findings

Glial failure leads to seizure-like activity in the model.

Glial activity determines the stability of persistent neural states.

Model predicts experimental outcomes related to ionic dynamics and excitability.

Abstract

In these companion papers, we study how the interrelated dynamics of sodium and potassium affect the excitability of neurons, the occurrence of seizures, and the stability of persistent states of activity. We seek to study these dynamics with respect to the following compartments: neurons, glia, and extracellular space. We are particularly interested in the slower time-scale dynamics that determine overall excitability, and set the stage for transient episodes of persistent oscillations, working memory, or seizures. In this second of two companion papers, we present an ionic current network model composed of populations of Hodgkin-Huxley type excitatory and inhibitory neurons embedded within extracellular space and glia, in order to investigate the role of micro-environmental ionic dynamics on the stability of persistent activity. We show that these networks reproduce seizure-like activity if glial cells fail to maintain the proper micro-environmental conditions surrounding neurons, and produce several experimentally testable predictions. Our work suggests that the stability of persistent states to perturbation is set by glial activity, and that how the response to such perturbations decays or grows may be a critical factor in a variety of disparate transient phenomena such as working memory, burst firing in neonatal brain or spinal cord, up states, seizures, and cortical oscillations.