Sensory coding is impaired in rat absence epilepsy

Abstract

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.

Absence epilepsy might build its own nest

“…Studer et al . () reported important structural differences between the epileptic and healthy rodent brain, but their study could not differentiate whether these alterations are contributors to the epileptogenesis or part of a compensatory mechanism which tries to dampen the effect of seizures on the cortical circuitry. It is known that during epileptogenesis SWDs progressively become more synchronous with a sharper, more pronounced spike component, reflecting that cortical units are firing more and more synchronously driven by the seizure activity (Jarre et al .…”

“…The work of Studer et al . () revealed important structural alterations of the epileptic brain of GAERS and highlighted that the altered structure of the somatosensory cortex might process sensory information in a substantially different way. Although absence epilepsy is considered a relatively benign form of epilepsy, it is often accompanied by comorbidities.…”

“…In light of this, it is possible that the methods used by Studer et al . () might underestimate the functional impairment of somatosensory cortex, given that other brain regions are able to compensate for the missing or non‐functional somatosensory cortex.…”

“…One caveat of the study of Studer et al . () is that the applied methods did not make it possible to evaluate the function of inhibitory neurons or the dynamics of cortical inhibition. Multi‐unit activity analysis does not provide sufficient resolution to observe the temporal relationship between the firing of pyramidal cells and interneurons or between the different interneuron subpopulations.…”

“…The study of Studer et al . () sets the stage for new hypotheses, although simultaneous unit recordings and a detailed connectivity analysis in all the cortical layers are required in the seizure onset zone and in other non‐sensory cortical areas. Only such experiments can further elucidate the impact of seizing on the cortical microcircuitry in absence epilepsy.…”