Cognitive Impairments in Touchscreen-based Visual Discrimination and Reversal Learning in Genetic Absence Epilepsy Rats from Strasbourg

Abstract

Absence Epilepsy (AE) is associated with recurrent losses of awareness and synchronous bilateral spike-wave discharges (SWDs). While seizures do not generally continue into adulthood, cognitive and behavioral comorbidities persist. One preclinical model used to investigate AE is the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) which consistently have bilateral SWDs and similar behavioral profiles. In this experiment, we characterized discrimination learning and behavioral flexibility in female and male GAERS (n = 7 per sex) and Non-Epileptic Controls (NEC; n = 8 per sex) in a touchscreen-based version of visual discrimination (VD) and reversal learning (RL). We found that, on average, female GAERS required more sessions (12.3) to complete pretraining compared to female and male NEC (8.2 and 7.3, respectively) and male GAERS (9.4). In contrast, there was a sex-specific impairment during VD with male GAERS requiring more sessions on average (12.3) than male and female NEC (both 7.5) and female GAERS (8.3). Additionally, male GAERS completed >30% more selection and correction trials during VD and made >30% more errors.Both female and male GAERS required more sessions on average (9.1 and 10.7, respectively) of RL compared to female and male NEC (6.4 and 6.0 sessions, respectively). Accordingly, GAERS performed ∼30% more selection trials and correction trials compared to NEC, although only male GAERS made significantly more errors (>40%). Deficits in VD and RL were not associated with differences in correct or incorrect response latency, or reward collection latency, suggesting impairments are not due to alterations in locomotor activity or motivation. Together, these data suggest that GAERS have impaired behavioral flexibility and identify some sex-dependent differences. Thus, GAERS may be suitable for assessing the potential benefit of antiepileptic drugs on comorbid behavioral and cognitive deficits.