Sex-specific effects of Cacna1c haploinsufficiency on object recognition, spatial memory, and reversal learning capabilities in rats
Sex-specific effects of Cacna1c haploinsufficiency on object recognition, spatial memory, and reversal learning capabilities in rats
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DOI：
10.1016/j.nlm.2018.05.012
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发表时间：
2018-11-01
影响因子：
2.7
通讯作者：
Woehr, Markus
中科院分区：
文献类型：
--
作者：
Braun, Moria D.;Kisko, Theresa M.;Woehr, Markus
CACNA1C基因与多种主要神经精神疾病的病因密切相关，如双相情感障碍、重度抑郁症和精神分裂症，认知缺陷是一种常见特征。然而，目前尚不清楚CACNA1C变异通过何种机制提高了发生神经精神疾病的风险。本研究旨在研究新开发的遗传性Cacna1c大鼠模型的认知功能。具体来说，我们评估了杂合型Cacna1c（+/-）大鼠的空间学习和逆向学习以及物体识别记忆，并将其与野生型Cacna1c（+/+）雌雄同体对照进行了比较。我们的研究结果表明，Cacna1c（+/+）和Cacna1c（+/-）的动物都能够在7天的时间里学习径向迷宫的奖励臂结构。两组学生都表现出逆向学习模式，表明他们的能力完好无损。在雌性中，基因型差异在初始空间学习阶段很明显，Cacna1c（+/-）雌性表现出低活性和较少的混合错误。在雄性中，在两个学习阶段的探针试验中发现了差异，Cacna1c（+/-）大鼠在先前诱饵和未诱饵的手臂之间表现出更好的区分；以及有利于Cacna1c（+/+）动物的认知灵活性。在新物体识别任务中，所有实验组对奖励大小都很敏感，并且完全能够区分新物体和熟悉物体。综上所述，这些结果表明Cacna1c单倍不足对大鼠的（空间）记忆功能有轻微但积极的影响。
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.