Decreased overall neuronal activity in a rodent model of impaired consciousness during absence seizures

Abstract

Absence seizures are characterized by a brief behavioural impairment including apparent loss of consciousness. Neuronal mechanisms determining the behavioural impairment of absence seizures remain unknown, and their elucidation might highlight therapeutic options for reducing seizure severity. However, recent studies have questioned the similarity of animal spike-wave-discharges (SWD) to human absence seizures both behaviourally and neuronally. Here, we report that Genetic Absence Epilepsy Rats from Strasbourg recapitulate the decreased neuroimaging signals and loss of consciousness characteristic of human absence seizures. Overall neuronal firing is decreased but rhythmic in the somatosensory cortex and thalamus during these seizures. Interestingly, individual neurons in both regions tend to consistently express one of four distinct patterns of seizure-associated activity. These patterns differ in firing rate dynamics and in rhythmicity during seizure. One group of neurons showed a transient initial peak in firing at SWD onset, accounting for the brief initial increase in overall neuronal firing seen in cortex and thalamus. The largest group of neurons in both cortex and thalamus showed sustained decreases in firing during SWD. Other neurons showed either sustained increases or no change in firing. These findings suggest that certain classes of cortical and thalamic neurons may be particularly responsible for the paroxysmal oscillations and consequent loss of consciousness in absence epilepsy.

Higher-order thalamic nuclei facilitate the generalization and maintenance of spike-and-wave discharges of absence seizures

“…PO Connectivity and intrinsic cell dynamics are not homogeneous across PO, instead, there are distinct but overlapping input and output profiles (Casas-Torremocha et al, 2022, 2022; Guo et al, 2020) as well as highly varied burst patterns, that could explain the heterogeneity observed here (Desai and Varela, 2021). The complexity of thalamic neuronal dynamics at SWD onset extends to FO nuclei, where in VB neurons four groups of cells have been reported, including ‘onset peak’ and ‘sustained increase’ cells (McCafferty et al, 2021), similar to those reported here.…”