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.