Spike-wave discharges (SWDs) on the EEG during absence epilepsy are waxing and waning stages of corticothalamic hypersynchrony. While the somatosensory cortex contains an epileptic focus, the role of thalamic nuclei in SWD generation is debated. Here we assess the contribution of distinct thalamic nuclei through multiple-site unit recordings in a genetic rat model of absence epilepsy and cross-correlation analysis, revealing coupling strength and directionality of neuronal activity at high temporal resolution. Corticothalamic coupling increased and decreased during waxing and waning of SWD, respectively. A cortical drive on either sensory or higher order thalamic nuclei distinguished between onset and offset of SWD, respectively. Intrathalamic coupling steadily increased during maintained SWD activity, peaked at SWD offset, and subsequently displayed a sharp decline to baseline. The peak in intrathalamic coupling coincided with a sharp increase in coupling strength between reticular thalamic nucleus and somatosensory cortex. This increased influence of the inhibitory reticular thalamic nucleus is suggested to serve as a break for SWD activity. Overall, the data extend the cortical focus theory of absence epilepsy by identifying a regionally specific cortical lead over distinct thalamic nuclei, particularly also during waning of generalized epileptic discharges, thereby revealing a potential window and location for intervention.
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