Abstract
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.
Highlights
The thalamo-cortical system is a complex circuitry within the mammalian nervous system, whose oscillations are crucially implicated in various aspects of sensation, behavior and cognition including the regulation of wakefulness and sleep, attention and the level of consciousness experience[1,2]
These local miniature spike and wave discharges (SWDs) in the cortical local field potential (LFP) coincided with local spike locked unit activity recorded in somatosensory cortex (SCtx), while no such local epileptic miniature SWDs were found in any of the thalamic traces (χ2(number of local SWD in cortex vs number of local SWD in thalamus): p < 0.001)
The current study investigated coupling dynamics associated with the generation and termination of SWDs within the thalamocortical system of absence epileptic GAERS
Summary
The thalamo-cortical system is a complex circuitry within the mammalian nervous system, whose oscillations are crucially implicated in various aspects of sensation, behavior and cognition including the regulation of wakefulness and sleep, attention and the level of consciousness experience[1,2] Proper regulation of these functions are thought to rely on a balanced interplay of cellular dynamics between the different components of the thalamocortical loops. While the existence of a local cortical epileptic focus has been proposed in both humans as well as in genetic rat models of absence epilepsy[6,7,8,9], the contribution of different thalamic nuclei to the generation, maintenance and termination is less well understood. Intrathalamic coupling was assessed from simultaneous recordings of thalamic nuclei, to achieve a detailed and complete picture on both corticothalamic and thalamothalamic coupling dynamics including all relevant areas associated with the assumed focal generation and rapid generalization of SWDs, as well as to unravel network changes relevant for the spontaneous termination of SWDs
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