Cognitive comorbidities of experimental absence seizures are independent of anxiety

Abstract

Typical absence seizures (ASs) are brief periods of lack of consciousness, associated with 2.5-4 Hz spike-wave discharges (SWDs) in the EEG, which are highly prevalent in children and teenagers. The majority of probands in these young epileptic cohorts show neuropsychological comorbidities, including cognitive, memory and mood impairments, even after the seizures are pharmacologically controlled. Similar cognition and memory deficits have been reported in different, but not all, genetic animal models of ASs. However, since these impairments are subtle and highly task-specific their presence may be confounded by an anxiety-like phenotype and no study has tested anxiety and memory in the same animals. Moreover, the majority of studies used non-epileptic inbred animals as the only control strain and this may have contributed to a misinterpretation of these behavioural results. To overcome these issues, here we used a battery of behavioural tests to compare anxiety and memory in the same animals from the well-established inbred model of Genetic Absence Epilepsy Rats from Strasbourg (GAERS), their inbred strain of Non-Epileptic Control (NEC) strain (that lack ASs) and normal outbred Wistar rats. We found that GAERS do not exhibit increased anxiety-like behavior and neophobia compared to both NEC and Wistar rats. In contrast, GAERS show decreased spontaneous alternation, spatial working memory and cross-modal object recognition compared to both NEC and Wistar rats. Furthermore, GAERS preferentially used egocentric strategies to perform spatial memory tasks. In summary, these results provide solid evidence of memory deficits in GAERS rats that do not depend on an anxiety or neophobic phenotype. Moreover, the presence of differences between NEC and Wistar rats stresses the need of using both outbred and inbred control rats in behavioural studies involving genetic models of ASs.