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Spike-and-wave discharges of absence seizures in a sleep waves-constrained corticothalamic model

Dervinis, Martynas and Crunelli, Vincenzo ORCID: https://orcid.org/0000-0001-7154-9752 2023. Spike-and-wave discharges of absence seizures in a sleep waves-constrained corticothalamic model. Cns Neuroscience & Therapeutics 10.1111/cns.14204

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Abstract

Aims Recurrent network activity in corticothalamic circuits generates physiological and pathological EEG waves. Many computer models have simulated spike-and-wave discharges (SWDs), the EEG hallmark of absence seizures (ASs). However, these models either provided detailed simulated activity only in a selected territory (i.e., cortical or thalamic) or did not test whether their corticothalamic networks could reproduce the physiological activities that are generated by these circuits. Methods Using a biophysical large-scale corticothalamic model that reproduces the full extent of EEG sleep waves, including sleep spindles, delta, and slow (<1 Hz) waves, here we investigated how single abnormalities in voltage- or transmitter-gated channels in the neocortex or thalamus led to SWDs. Results We found that a selective increase in the tonic γ-aminobutyric acid type A receptor (GABA-A) inhibition of first-order thalamocortical (TC) neurons or a selective decrease in cortical phasic GABA-A inhibition is sufficient to generate ~4 Hz SWDs (as in humans) that invariably start in neocortical territories. Decreasing the leak conductance of higher-order TC neurons leads to ~7 Hz SWDs (as in rodent models) while maintaining sleep spindles at 7–14 Hz. Conclusion By challenging key features of current mechanistic views, this simulated ictal corticothalamic activity provides novel understanding of ASs and makes key testable predictions.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Biosciences
Funders: MRC
Date of First Compliant Deposit: 5 April 2023
Date of Acceptance: 24 March 2023
Last Modified: 04 Jul 2023 17:12
URI: https://orca.cardiff.ac.uk/id/eprint/158420

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