Characterization and genetic ablation of the CA2 subfield of the hippocampus

描述(申请人提供)：海马体结构是大脑的一个区域，对各种形式的学习和记忆至关重要。信息被认为是由海马体通过三突触通路处理的。在这个回路中，内嗅皮层输出到齿状回，而齿状回又连接到CA3。然后，CA3将信息发送到CA1，这是海马体的输出区。值得注意的是，CA2子场没有出现在这条线路上。CA2通常被忽略或与CA3组合在一起，通常逃脱了勘探，大概是因为它的规模相对较小，边界有些模糊。一些研究已经提出了海马区CA2亚区的重要作用；然而，这个亚区在行为动物中的相关性还没有被探索过。特定大脑区域的功能可以通过检查该区域病变的影响来推断。事实上，在患者H.M.的双侧内侧颞叶切除后，海马体在学习和记忆中的作用被阐明。类似地，CA2的损伤可以用来推断它在学习、记忆和疾病中的作用。由于CA2的体积相对较小，物理或化学损伤不够精确，无法在没有附带损害的情况下消融这一区域。为此，我们培育了CA2-Cre小鼠品系。这项应用的目标是使用这一CA2-CRE小鼠品系来仔细描述这一大脑区域的解剖特征，并观察CA2基因靶向损伤后在学习和记忆任务中的任何行为缺陷。这些研究有可能修改关于海马体回路的规范观点。此外，CA2还与精神分裂症和双相情感障碍等疾病有关。因此，阐明CA2的S在海马环路中的作用有助于进一步了解这些疾病的过程。

DESCRIPTION (provided by applicant): The hippocampal formation is a brain region that is critical for various forms of learning and memory. Information is thought to be processed by the hippocampal formation through the trisynaptic pathway. In this circuit, entorhinal cortex outputs to dentate gyrus, which in turn connects to CA3. CA3 then sends information to CA1, a hippocampal output area. Conspicuously absent from this circuit is the CA2 subfield. Usually ignored or grouped together with CA3, CA2 has generally escaped exploration presumably due to its relatively small size and somewhat ill-defined borders. A few studies have proposed an important role for the CA2 subfield of the hippocampus; however, the relevance of this subfield in a behaving animal has not been explored. The function of a particular brain region may be inferred by examining the effects of a lesion of that area. Indeed, the hippocampus's role in learning and memory was elucidated following the bilateral medial temporal lobe ablation of patient H.M. Similarly, a lesion of CA2 could be used to infer its role in learning, memory, and disease. Due to the relatively small size of CA2, physical or chemical lesions are not precise enough to ablate this region without collateral damage. To this end, we have generated a CA2- Cre mouse line. The goal of this application is to use this CA2-Cre mouse line to carefully characterize the anatomy of this brain region, and to observe any behavioral deficits in learning and memory tasks following a genetically targeted lesion of CA2. These studies have the potential to revise canonical views of hippocampal circuitry. Moreover, CA2 has been implicated in diseases such as schizophrenia and bipolar disorder. Hence, elucidating CA2's contribution to the hippocampal circuit could further understanding of these disease processes.