Further refining the boundaries of the hippocampus CA2 with gene expression and connectivity: Potential subregions and heterogeneous cell types

Abstract

Over the last two decades, the definition of hippocampal area CA2 has evolved from Lorente de Nó's original Golgi-based morphological description with the discovery of specific CA2 gene expression markers. Exploiting the specificity of these molecules has allowed for the genetic dissection of CA2 structure and function in transgenic mice. With this change in criteria, the anatomical boundaries of the CA2 have expanded across the hippocampal axis but the CA2's full rostrocaudal extent is not consistently delineated across atlases. The Hippocampus Gene Expression Atlas (HGEA) provides a comprehensive map of 20 gene expression domains across the entire mouse hippocampus including the CA2. In this commentary, I will review the consensus gene expression patterns that demarcate the expanded CA2 boundaries in the HGEA. Using DropViz single-cell transcriptomics and Mouse Connectome Project connectomics data, I will then suggest potential differences in CA2 cell type heterogeneity and connectivity that may identify and characterize further CA2 subregions.