CACNA1C, a gene that encodes an alpha-1 subunit of L-type voltage-gated calcium channels, has been strongly associated with psychiatric disorders including schizophrenia and bipolar disorder. An important objective is to understand how variation in this gene can lead to an increased risk of psychopathology. Altered associative learning has also been implicated in the pathology of psychiatric disorders, particularly in the manifestation of psychotic symptoms. In this study, we utilize auditory-cued fear memory paradigms in order to investigate whether associative learning is altered in rats hemizygous for the Cacna1c gene. Cacna1c hemizygous (Cacna1c^+/−) rats and their wild-type littermates were exposed to either delay, trace, or unpaired auditory fear conditioning. All rats received a Context Recall (24 h post-conditioning) and a Cue Recall (48 h post-conditioning) to test their fear responses. In the delay condition, which results in strong conditioning to the cue in wild-type animals, Cacna1c^+/− rats showed increased fear responses to the context. In the trace condition, which results in strong conditioning to the context in wild-type animals, Cacna1c^+/− rats showed increased fear responses to the cue. Finally, in the unpaired condition, Cacna1c^+/− rats showed increased fear responses to both context and cue. These results indicate that Cacna1c heterozygous rats show aberrantly enhanced fear responses to inappropriate cues, consistent with key models of psychosis.

中文翻译：

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Cacna1c 半合性导致对中性刺激的异常恐惧调节。


CACNA1C 是一种编码 L 型电压门控钙通道 alpha-1 亚基的基因，与精神分裂症和双相情感障碍等精神疾病密切相关。一个重要的目标是了解该基因的变异如何导致精神病理学风险增加。联想学习的改变也与精神疾病的病理学有关，特别是与精神病症状的表现有关。在这项研究中，我们利用听觉提示的恐惧记忆范例来研究Cacna1c基因半合子大鼠的联想学习是否发生改变。 Cacna1c半合子 ( Cacna1c ^+/- ) 大鼠及其野生型同窝小鼠接受延迟、微量或不配对的听觉恐惧条件反射。所有大鼠均接受情境回忆（条件反射后 24 小时）和提示回忆（条件反射后 48 小时）以测试其恐惧反应。在延迟条件下，野生型动物对提示产生强烈的条件反射， Cacna1c ^+/-大鼠对环境表现出更强的恐惧反应。在跟踪条件下，野生型动物对环境产生强烈的条件反射， Cacna1c ^+/-大鼠对提示表现出更强的恐惧反应。最后，在未配对的情况下， Cacna1c ^+/-大鼠对情境和提示表现出更强的恐惧反应。这些结果表明， Cacna1c杂合子大鼠对不适当的线索表现出异常增强的恐惧反应，与精神病的关键模型一致。