SUMMARYPurpose: The origin of bilateral synchronous spike-andwave discharges (SWDs) that underlie absence seizures has been widely debated. Studies in genetic rodent models suggest that SWDs originate from a restricted region in the somatosensory cortex. The properties of this initiation site remain unknown. Our goal was to characterize the interictal, preictal and ictal neuronal activity in the primary and secondary cortical regions (S1, S2) and in the adjacent insular cortex (IC) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Methods: We performed electroencephalography (EEG) recordings in combination with multisite local field potential (LFP) and single cell juxtacellular recordings, and cortical electrical stimulations, in freely moving rats and those under neurolept-anesthesia.Key Findings: The onset of the SWDs was preceded by 5-9 Hz field potential oscillations, which were detected earlier in S2 and IC than in S1. Sustained SWDs could be triggered by a 2-s train of 7-Hz electrical stimuli at a lower current intensity in S2 than in S1. In S2 and IC, subsets of neurons displayed rhythmic firing (5-9 Hz) in between seizures. S2 and IC layers V and VI neurons fired during the same time window, whereas in S1 layer VI, neurons fired before layer V neurons. Just before the spike component of each SW complex, short-lasting high-frequency oscillations consistently occurred in IC 20 msec before S1. Significance: Our findings demonstrate that the S2/IC cortical areas are a critical component of the macronetwork that is responsible for the generation of absencerelated SWDs.

Our results show alterations in cortico-thalamo-cortical local and network properties following ICV administration of NPY, suggesting mechanisms of SWD suppression in GAERS. Cellular and network alteration of NRT activity, resulting from a direct action of NPY, may be a contributor to this effect.

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