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Active avoidance learning in WAG/Rij rats with genetic predisposition to absence epilepsy
Brain Research Bulletin ( IF 3.5 ) Pub Date : 2020-10-13 , DOI: 10.1016/j.brainresbull.2020.10.007
Evgenia Sitnikova 1 , Kirill Smirnov 1
Affiliation  

Neurological disorders are often accompanied by impairment of memory, attention deficit that cause learning difficulties. Better understanding of learning problems in neurological patients might help to improve the quality of their life. Here we studied the character of fear-based associative learning using the standard active avoidance test in WAG/Rij rats with genetic predisposition to absence epilepsy. Electroencephalographic properties of spike-wave seizures (i.e., hallmarks of absence epilepsy) were examined at the age of 5 and 7 m. Around 24 % of rats did not express epileptic activity despite genetic predisposition. In the active avoidance test, 6 m old rats with the epileptic phenotype needed more trails to obtain the first avoidance than non-epileptic rats, but showed the same number of avoidances to reach the learning criterion. The total time of spike-wave activity positively correlated with the outcomes of avoidance performance only in subjects with severe epilepsy, but not in subjects with mild epilepsy.

In order to evaluate early sensory (epigenetic) factors governing cognitive comorbidities in adult WAG/Rij rats, we performed bilateral whisker trimming during PN1-8 and PN9-16. This led to a quicker development of SWD, but did not influence cognitive abilities at the age of 6 m.

In summary, epileptic WAG/Rij rats had difficulties with executive functions before the first avoidance of adverse stimulus, rather than impairment of memory after the first avoidance. Our data assume that cognitive comorbidities in epileptic WAG/Rij rats primarily may relate to executive deficit during the initial stage of avoidance test and secondary - to impairment of short-term memory. This fits well to outcomes of clinical studies in patients with generalized epilepsy.



中文翻译:

具有失神癫痫遗传易感性的 WAG/Rij 大鼠的主动回避学习

神经系统疾病通常伴随着记忆障碍、注意力缺陷导致学习困难。更好地了解神经系统患者的学习问题可能有助于提高他们的生活质量。在这里,我们使用标准主动回避测试在具有失神癫痫遗传倾向的 WAG/Rij 大鼠中研究了基于恐惧的联想学习的特征。在 5 和 7 m 时检查了棘波癫痫发作的脑电图特性(即失神癫痫的标志)。尽管有遗传倾向,但大约 24% 的大鼠没有表现出癫痫活动。在主动回避试验中,与非癫痫大鼠相比,6 m 龄具有癫痫表型的大鼠需要更多的路径才能获得第一次回避,但达到学习标准的回避次数相同。

为了评估控制成年 WAG/Rij 大鼠认知合并症的早期感觉(表观遗传)因素,我们在 PN1-8 和 PN9-16 期间进行了双侧胡须修剪。这导致 SWD 的更快发展,但不会影响 6 m 时的认知能力。

总之,癫痫 WAG/Rij 大鼠在第一次避免不利刺激之前有执行功能困难,而不是第一次避免后记忆受损。我们的数据假设癫痫 WAG/Rij 大鼠的认知合并症主要可能与回避测试初始阶段的执行缺陷和继发性 - 短期记忆障碍有关。这非常符合全身性癫痫患者的临床研究结果。

更新日期:2020-10-30
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