Gene Expression Patterns Reflect Anatomical And Physiological Variation In Adult Mouse Medial Entorhinal Cortex

Using mRNA in situ hybridization data and tools from the Allen Brain Atlas, we explored whether patterns of gene expression in medial entorhinal cortex (MEC) map on to physiological variation in cellular properties. The MEC is a critical component of memory circuitry and possesses cells with diverse functions, including cells that exhibit grid-like spatial firing patterns during exploration (Hafting et al., 2005). Grid cell properties vary along a dorsal-ventral gradient (Hafting et al., 2005), an organization that is mirrored by a gradient in integration of synaptic responses (Garden et al., 2008). We sought to identify spatially patterned and layer-specific genes using a combination of unbiased, automated analyses of expression levels and enrichment, NeuroBlast searches for genes with correlated expression patterns, and manual validation. We examined functional enrichment, disease links, and homology across species within and across gene lists. We also tested whether genes with similar expression patterns are under common transcriptional control by performing a transcription factor binding site screen of constrained elements in the mouse genome and mapping them to MEC genes. Thousands of genes exhibit patterned or layer-specific expression across MEC, hundreds of which show a strong dorsal-ventral gradient in layer II where grid cells are most frequently found. Using gene ontology analysis we find functional enrichment of ion transport, synaptic transmission and behavioural functions in MEC layer-enriched genes but not in uniformly expressed genes. Furthermore, dendritic, synaptic and projection-located genes are highly overrepresented. We also identify transcription factor families that show clustered patterns of enrichment within patterned-gene lists. It will be important to consider how patterns of enrichment in MEC compare with those of neocortex and hippocampus.