Characterization and genetic ablation of the CA2 subfield of the hippocampus

描述（由申请人提供）：海马结构是对各种形式的学习和记忆至关重要的大脑区域。信息被认为是由海马结构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，齿状回又连接到CA 3。然后，CA 3将信息发送到海马输出区域CA 1。在这个回路中明显缺少的是CA 2亚区。CA 2通常被忽略或与CA 3组合在一起，通常逃避探索，大概是因为它相对较小的尺寸和边界不明确。 一些研究已经提出了海马CA 2子区域的重要作用，然而，该子区域在行为动物中的相关性尚未被探索。特定脑区的功能可以通过检查该区域病变的影响来推断。事实上，海马在学习和记忆中的作用在患者H. M.同样，CA 2的损伤可以用来推断其在学习、记忆和疾病中的作用。 由于CA 2的尺寸相对较小，物理或化学损伤不够精确，无法在不造成附带损伤的情况下消融该区域。为此，我们生成了CA 2- Cre小鼠系。本申请的目的是使用该CA 2-Cre小鼠系仔细表征该脑区的解剖结构，并观察CA 2遗传靶向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电路的经典观点。此外，CA 2与精神分裂症和双相情感障碍等疾病有关。因此，阐明CA 2对海马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.