Neuronal Physiology of Generalized Seizures: The 4 Horsemen of Absence Epilepsy

Decreased but Diverse Activity of Cortical and Thalamic Neurons in Consciousness-Impairing Rodent Absence Seizures McCafferty C, Gruenbaum BF, Tung R, Li JJ, Zheng X, Salvino P, Vincent P, Kratochvil Z, Ryu JH, Khalaf A, Swift K, Akbari R, Islam W, Antwi P, Johnson EA, Vitkovskiy P, Sampognaro J, Freedman IG, Kundishora A, Depaulis A, David F, Crunelli V, Sanganahalli BG, Herman P, Hyder F, Blumenfeld H. Nat Commun. 2023;14(1):117. doi:10.1038/s41467-022-35535-4 Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40-60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.