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.