Roebuck Andrew J, An Lei, Marks Wendie N, Sun Ninglei, Snutch Terrance P, Howland John G
Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, Canada.
The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China.
Neuroscience. 2020 Mar 15;430:105-112. doi: 10.1016/j.neuroscience.2020.01.028. Epub 2020 Feb 1.
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.
失神癫痫（AE）与意识反复丧失及双侧同步棘慢波放电（SWD）有关。虽然癫痫发作通常不会持续到成年，但认知和行为合并症会持续存在。一种用于研究AE的临床前模型是来自斯特拉斯堡的遗传性失神癫痫大鼠（GAERS），其始终具有双侧SWD和相似的行为特征。在本实验中，我们在基于触摸屏的视觉辨别（VD）和逆向学习（RL）版本中，对雌性和雄性GAERS（每组性别n = 7）和非癫痫对照（NEC；每组性别n = 8）的辨别学习和行为灵活性进行了表征。我们发现，平均而言，与雌性和雄性NEC（分别为8.2和7.3）以及雄性GAERS（9.4）相比，雌性GAERS完成预训练需要更多的实验次数（12.3）。相比之下，在VD期间存在性别特异性损伤，雄性GAERS平均需要更多的实验次数（12.3），多于雄性和雌性NEC（均为7.5）以及雌性GAERS（8.3）。此外，雄性GAERS在VD期间完成的选择和校正试验多>30%，且错误多>30%。与雌性和雄性NEC（分别为6.4和6.0次实验）相比，雌性和雄性GAERS平均需要更多的RL实验次数（分别为9.1和10.7）。因此，与NEC相比，GAERS进行的选择试验和校正试验多约30%，尽管只有雄性GAERS出现显著更多的错误（>40%）。VD和RL中的缺陷与正确或错误反应潜伏期或奖励收集潜伏期的差异无关，这表明损伤并非由于运动活动或动机的改变。总之，这些数据表明GAERS的行为灵活性受损，并确定了一些性别依赖性差异。因此，GAERS可能适用于评估抗癫痫药物对合并的行为和认知缺陷的潜在益处。
