The epileptogenic processes leading to recurrent seizures in Genetic Epilepsies are largely unknown. Using the Genetic Absence Epilepsy Rat from Strasbourg, we investigated in vivo the network and single neuron mechanisms responsible for the early emergence of epileptic activity. Local field potential recordings in the primary somatosensory cortex (SoCx), from the second post-natal week to adulthood, showed that immature cortical discharges progressively evolved into typical spike-and-wave discharges following a 3-step maturation process. Intracellular recordings from deep-layer SoCx neurons revealed that this maturation was associated with an age-dependent increase in cortical neurons intrinsic excitability, combining a membrane depolarization and an enhancement of spontaneous firing rate with a leftward shift in their input-output relation. These cellular changes were accompanied by a progressive increase in the strength of the local synaptic activity associated with a growing propensity of neurons to generate synchronized oscillations. Chronic anti-absence treatment before the occurrence of mature cortical discharges did not alter epileptogenesis or the drug efficiency at adulthood. These findings demonstrate that recurrent absence seizures originate from the progressive acquisition of pro-ictogenic properties in SoCx neurons and networks during the post-natal period and that these processes cannot be interrupted by early anti-absence treatment.

Key points Absence epilepsy is characterized by the occurrence of spike‐and‐wave discharges concomitant with an alteration of consciousness and is associated with cognitive comorbidities. In a genetic model of absence epilepsy in the rat, the genetic absence epilepsy rat from Strasbourg (GAERS), spike‐and‐wave discharges are shown to be initiated in the barrel field primary somatosensory cortex that codes whisker‐related information, therefore playing an essential role in the interactions of rodents with their environment. Sensory‐information processing is impaired in the epileptic barrel field primary somatosensory cortex of GAERS, with a delayed sensory‐evoked potential and a duplicated neuronal response to whisker stimulation in in vivo extracellular recordings. Yet, GAERS present no defaults of performance in a texture discrimination task, suggesting the existence of a compensatory mechanism within the epileptic neuronal network. The results of the present study indicate that physiological primary functions are processed differently in an epileptic cortical network. Abstract Several neurodevelopmental pathologies are associated with disorganized cortical circuits that may alter primary functions such as sensory processes. In the present study, we investigated whether the function of a cortical area is altered in the seizure onset zone of absence epilepsy, a prototypical form of childhood genetic epilepsy associated with cognitive impairments. We first combined in vivo multichannel electrophysiological recordings and histology to precisely localize the seizure onset zone in the genetic absence epilepsy rat from Strasbourg (GAERS). We then investigated the functionality of this epileptic zone using extracellular silicon probe recordings of sensory‐evoked local field potentials and multi‐unit activity, as well as a behavioural test of texture discrimination. We show that seizures in this model are initiated in the barrel field part of the primary somatosensory cortex and are associated with high‐frequency oscillations. In this cortex, we found an increased density of parvalbumin‐expressing interneurons in layer 5 in GAERS compared to non‐epileptic Wistar rats. Its functional investigation revealed that sensory abilities of GAERS are not affected in a texture‐discrimination task, whereas the intracortical processing of sensory‐evoked information is delayed and duplicated. Altogether, these results suggest that absence seizures are associated with an increase of parvalbumin‐inhibitory neurons, which may promote the functional relationship between epileptic oscillations and high‐frequency activities. Our findings suggest that cortical circuits operate differently in the epileptic onset zone and may adapt to maintain their ability to process highly specialized information.