Specific Proteomes of Hippocampal Regions CA2 and CA1 Reveal Proteins Linked to the Unique Physiology of Area CA2

The hippocampus is well established as an essential brain center for learning and memory. Within the hippocampus, recent studies show that area CA2 is important for social memory and is an anomaly compared to its better-understood neighboring region, CA1. Unlike CA1, CA2 displays a lack of typical synaptic plasticity, enhanced calcium buffering and extrusion, and resilience to cell death following injury. Although recent studies have identified multiple molecular markers of area CA2, the proteins that mediate the unique physiology, signaling, and resilience of this region are unknown. Using a transgenic GFP-reporter mouse line that expresses eGFP in CA2, we were able to perform targeted dissections of area CA2 and CA1 for proteomic analysis. We identified over 100 proteins with robustly enriched expression in area CA2 compared to CA1. Many of these proteins, including RGS14 and NECAB2, have already been shown to be enriched in CA2 and important for its function, while many more merit further study in the context of enhanced expression in this enigmatic brain region. Furthermore, we performed a comprehensive analysis of the entire data set (>2300 proteins) using a weighted protein co-expression network analysis. This identified eight distinct co-expressed patterns of protein co-enrichment associated with increased expression in area CA2 tissue (compared to CA1). The novel data set we present here reveals a specific CA2 hippocampal proteome, laying the groundwork for future studies and a deeper understanding of area CA2 and the proteins mediating its unique physiology and signaling.