Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are linked to impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.

中文翻译：

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Bardet-Biedl综合征的小鼠模型损害了恐惧记忆，可通过锂疗法挽救

原发性纤毛是存在于大多数细胞上的微管细胞器，可调节许多生理过程，范围从维持能量稳态到肾功能。但是，这些结构在行为调节中的作用仍然未知。为了研究纤毛在行为中的作用，我们采用了人类纤毛病Bardet-Biedl综合征（BBS）的小鼠模型。在这里，我们证明BBS小鼠在情境恐惧条件（一种关联学习形式）中具有明显的损伤。此外，我们表明，出生后BBS基因功能的缺失以及先天性缺失（特别是在前脑中的缺失）会削弱环境恐惧条件。分析表明，这些行为障碍不是海马长时程增强受损的结果。然而，我们的结果表明，这些行为障碍与海马神经发生受损有关。用氯化锂进行的为期两周的治疗可部分恢复海马神经元的增殖，从而挽救情境恐惧条件。总体而言，我们的研究结果表明纤毛基因在海马神经发生和长期情境恐惧调节中具有新型作用。