Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Drive, New York, New York 10032, USA.
1] Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Drive, New York, New York 10032, USA [2] Department of Pharmacology, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Drive, New York, New York 10032, USA.
Nature. 2014 Apr 3;508(7494):88-92. doi: 10.1038/nature13028. Epub 2014 Feb 23.
The hippocampus is critical for encoding declarative memory, our repository of knowledge of who, what, where and when. Mnemonic information is processed in the hippocampus through several parallel routes involving distinct subregions. In the classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to dentate gyrus to CA3 and then to CA1, the main hippocampal output. Genetic lesions of EC (ref. 3) and hippocampal dentate gyrus (ref. 4), CA3 (ref. 5) and CA1 (ref. 6) regions have revealed their distinct functions in learning and memory. In contrast, little is known about the role of CA2, a relatively small area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic circuit linking EC input with CA1 output. Here we report a novel transgenic mouse line that enabled us to selectively examine the synaptic connections and behavioural role of the CA2 region in adult mice. Genetically targeted inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory--the ability of an animal to remember a conspecific--with no change in sociability or several other hippocampus-dependent behaviours, including spatial and contextual memory. These behavioural and anatomical results thus reveal CA2 as a critical hub of sociocognitive memory processing.
海马体对于陈述性记忆的编码至关重要,我们的知识库包括了关于谁、什么、哪里和何时的知识。记忆信息通过涉及不同子区域的几个平行途径在海马体中进行处理。在经典的三突触通路中,信息从内嗅皮层 (EC) 传递到齿状回,再传递到 CA3,然后传递到 CA1,这是海马体的主要输出。对 EC(参考文献 3)和海马齿状回(参考文献 4)、CA3(参考文献 5)和 CA1(参考文献 6)区域的遗传损伤揭示了它们在学习和记忆中的不同功能。相比之下,CA2 的作用知之甚少,CA2 是位于 CA3 和 CA1 之间的一个相对较小的区域,它形成了一个强大的双突触回路的枢纽,将 EC 输入与 CA1 输出连接起来。在这里,我们报告了一种新型的转基因小鼠品系,使我们能够在成年小鼠中选择性地研究 CA2 区域的突触连接和行为作用。CA2 锥体神经元的基因靶向失活导致明显的社交记忆丧失——动物记住同类的能力——而社交性或其他几种依赖于海马体的行为(包括空间和上下文记忆)没有变化。这些行为和解剖学结果表明 CA2 是社会认知记忆处理的关键枢纽。