Hippocampal Wnt3a is Necessary and Sufficient for Contextual Fear Memory Acquisition and Consolidation
Hippocampal Wnt3a is Necessary and Sufficient for Contextual Fear Memory Acquisition and Consolidation
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海马 Wnt3a 对于情境恐惧记忆的获取和巩固是必要且充分的
DOI：
10.1093/cercor/bhu121
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chen Zhe-Yu
中科院分区：
文献类型：
--
作者：
Xu Ning;Zhou Wen-Juan;Wang Yue;Huang Shu-Hong;Li Xian;Chen Zhe-Yu
Wnt信号通路在发育过程中起关键作用。然而，到目前为止，wnt在成人学习和记忆中的作用仍然没有得到很好的理解。本研究旨在探讨wnt在成年小鼠海马依赖性情境恐惧条件反射（CFC）记忆形成中的作用和机制。CFC训练诱导了Wnt3a的分泌和表达，并激活了其下游的Wnt/Ca2+和Wnt/β-catenin信号通路。海马内注入Wnt3a抗体会影响CFC的获取和巩固，但不会影响CFC的表达。使用Wnt拮抗剂sFRP1或典型的Wnt抑制剂Dkk1，我们发现Wnt/Ca2+和Wnt/β-catenin信号通路分别参与获取和巩固。此外，我们发现Wnt3a信号不仅是CFC记忆的必要条件，而且是充分条件。海马内注入外源性Wnt3a可增强CFC的获取和巩固。在DH中过表达组成型活性β-catenin可以弥补CFC记忆巩固的缺陷，但不能弥补注射Wnt3a抗体诱导的获取，说明β-catenin信号通路在Wnt3a下游作用介导CFC记忆巩固。我们的研究可能有助于进一步了解Wnt3a在不同记忆阶段依赖于不同信号通路的精确调控。
The Wnt signaling pathway plays critical roles in development. However, to date, the role of Wnts in learning and memory in adults is still not well understood. Here, we aimed to investigate the roles and mechanisms of Wnts in hippocampal-dependent contextual fear conditioning (CFC) memory formation in adult mice. CFC training induced the secretion and expression of Wnt3a and the activation of its downstream Wnt/Ca2+and Wnt/β-catenin signaling pathways in the dorsal hippocampus (DH). Intrahippocampal infusion of Wnt3a antibody impaired CFC acquisition and consolidation, but not expression. Using the Wnt antagonist sFRP1 or the canonical Wnt inhibitor Dkk1, we found that Wnt/Ca2+and Wnt/β-catenin signaling pathways were involved in acquisition and consolidation, respectively. Moreover, we found Wnt3a signaling is not only necessary but also sufficient for CFC memory. Intrahippocampal infusion of exogenous Wnt3a could enhance acquisition and consolidation of CFC. Overexpression of constitutively active β-catenin in the DH could rescue the deficit in CFC memory consolidation, but not acquisition induced by Wnt3a antibody injection, which suggests β-catenin signaling pathway acts downstream of Wnt3a to mediate CFC memory consolidation. Our study may help further the understanding of the precise regulation of Wnt3a in differential memory phases depending on divergent signaling pathways.