Characterization and genetic ablation of the CA2 subfield of the hippocampus

描述（由申请人提供）：海马体是大脑的一个区域，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将信息发送到海马输出区CA1。CA2子场明显不在这个回路中。CA2通常被忽略或与CA3组合在一起，通常由于其相对较小的尺寸和一些不明确的边界而逃避探索。一些研究提出了海马CA2亚场的重要作用；然而，这一分支领域在行为动物中的相关性尚未被探索。大脑某一特定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H.M.患者的双侧内侧颞叶消融后，海马体在学习和记忆中的作用得到了阐明。类似地，CA2的病变可以用来推断其在学习、记忆和疾病中的作用。由于CA2相对较小，物理或化学损伤不足以精确消融该区域而不造成附带损伤。为此，我们产生了一个CA2- Cre小鼠系。本应用程序的目的是使用这种CA2- cre小鼠系来仔细表征该大脑区域的解剖结构，并观察遗传靶向CA2病变后学习和记忆任务中的任何行为缺陷。这些研究有可能修订海马回路的规范观点。此外，CA2与精神分裂症和双相情感障碍等疾病有关。因此，阐明CA2对海马体回路的贡献可以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. PUBLIC HEALTH RELEVANCE: Schizophrenia and bipolar-1 are common psychiatric illnesses that have a combined lifetime prevalence of 1.11% (Perala et al., 2007). The understudied hippocampal subfield CA2 has been implicated in these disease processes (Benes et al., 1998). This application aims to elucidate CA2's function in the hippocampus so that its role in learning, memory, and psychiatric disease may be further understood.