Thalamic hubs as early sources of global neuronal synchrony in absence epilepsy

Generalized seizures reflect a pathological state of sudden, global neuronal hypersynchrony. The mechanisms that support the initiation and maintenance of such synchrony remain unknown. Using simultaneous single-unit and electrocorticographic recordings in two mouse models of absence epilepsy, we evaluated the activity of approximately 2,000 individual neurons across 26 brain structures. By doing so, we resolved the temporal progression of single neuron activity prior to and during generalized seizures. Surprisingly, we observed that rhythmic, synchronized activity emerges early and gradually in both thalamus and cortex. Moreover, while we observe that individual neurons across most structures fire rhythmically and synchronously during seizures, a small subset of thalamic nuclei stand out as hubs, displaying activity that is strongly correlated across multiple regions. Thus, our findings collectively highlight the thalamus as an early driver of global and pathological neuronal hypersynchrony.