Defining a molecular atlas of the hippocampus using DNA microarrays and high-throughput in situ hybridization

The hippocampus consists of a series of cytoarchitecturally discrete subregions that can be distinguished from one another on the basis of morphology, connectivity, and electrophysiological properties. To understand the molecular underpinnings for these differences, DNA microarrays were used to find genes predicted to be enriched in subregions CA1, CA3, and the dentate gyrus, and >100 of these genes were subsequently analyzed using in situ hybridization to obtain cellular-level localization of their transcripts. The most striking commonality among the resulting patterns of gene expression is the extent to which cytoarchitectural boundaries within the hippocampus are respected, although the complexity of these patterns could not have been predicted on the basis of the microarray data alone. Among those genes with expression that can be characterized as "restricted" to neurons in one or more subregions of the hippocampus are a number of signal transduction molecules, transcription factors, calcium-binding proteins, and carbohydrate-modifying enzymes. These results suggest that important determinants of the unique identities of adult hippocampal neurons are differential signal transduction, regulation of gene expression, calcium homeostasis, and the maintenance of a unique extracellular milieu. Furthermore, the extremely high correlation between microarray data and in situ expression demonstrates the great utility of using DNA microarrays to genetically profile discrete brain regions.