Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenberg-Str. 18, D-35032 Marburg, Germany.
Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil.
Neurobiol Learn Mem. 2018 Nov;155:543-555. doi: 10.1016/j.nlm.2018.05.012. Epub 2018 May 23.
The CACNA1C gene is strongly implicated in the etiology of multiple major neuropsychiatric disorders, such as bipolar disorder, major depression, and schizophrenia, with cognitive deficits being a common feature. It is unclear, however, by which mechanisms CACNA1C variants advance the risk of developing neuropsychiatric disorders. This study set out to investigate cognitive functioning in a newly developed genetic Cacna1c rat model. Specifically, spatial and reversal learning, as well as object recognition memory were assessed in heterozygous Cacna1c rats and compared to wildtype Cacna1c littermate controls in both sexes. Our results show that both Cacna1c and Cacna1c animals were able to learn the rewarded arm configuration of a radial maze over the course of seven days. Both groups also showed reversal learning patterns indicative of intact abilities. In females, genotype differences were evident in the initial spatial learning phase, with Cacna1c females showing hypo-activity and fewer mixed errors. In males, a difference was found during probe trials for both learning phases, with Cacna1c rats displaying better distinction between previously baited and non-baited arms; and regarding cognitive flexibility in favor of the Cacna1c animals. All experimental groups proved to be sensitive to reward magnitude and fully able to distinguish between novel and familiar objects in the novel object recognition task. Taken together, these results indicate that Cacna1c haploinsufficiency has a minor, but positive impact on (spatial) memory functions in rats.
CACNA1C 基因强烈提示多种主要神经精神疾病的病因，如双相情感障碍、重度抑郁症和精神分裂症，认知缺陷是其常见特征。然而，CACNA1C 变体通过何种机制增加神经精神疾病的风险尚不清楚。本研究旨在研究新开发的遗传 Cacna1c 大鼠模型中的认知功能。具体来说，在雄性和雌性杂合子 Cacna1c 大鼠和野生型 Cacna1c 同窝对照中评估空间和反转学习以及物体识别记忆。我们的结果表明，Cacna1c 和 Cacna1c 动物都能够在七天的时间内学会放射状迷宫的奖励臂构型。两组动物都表现出了完整能力的反转学习模式。在雌性中，Cacna1c 雌性在初始空间学习阶段表现出活动减少和混合错误减少，存在基因型差异。在雄性中，在两个学习阶段的探针试验中发现了差异，Cacna1c 大鼠在以前的诱饵和非诱饵臂之间表现出更好的区分；并且在认知灵活性方面，Cacna1c 动物表现更好。所有实验组均对奖励幅度敏感，并能够在新物体识别任务中完全区分新物体和熟悉物体。总之，这些结果表明 Cacna1c 杂合不足对大鼠（空间）记忆功能有轻微但积极的影响。
