In the limbic brain,mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) both function as receptors for the naturally occurring glucocorticoids (corticosterone/cortisol) butmediate distinct effects on cellular physiology via transcriptionalmechanisms. The transcriptional basis for specificity of these MRvs GR-mediated effects is unknown. To address this conundrum, we have identified the extent ofMR/GR DNA-binding selectivity in the rat hippocampus using chromatin immunoprecipitation followed by sequencing. We found 918 and 1450 nonoverlapping binding sites for MR and GR, respectively. Furthermore, 475 loci were co-occupied byMR and GR. De novo motif analysis resulted in a similar binding motif for both receptors at 100% of the target loci, which matched the known glucocorticoid response element (GRE). In addition, the Atoh/NeuroD consensus sequence was found in co-occurrence with all MR-specific binding sites butwas absent forGR-specific orMR-GR overlapping sites. Basic helix-loop-helix family members Neurod1, Neurod2, and Neurod6 showed hippocampal expression and were hypothesized to bind the Atohmotif.Neurod2was detected at rat hippocampalMRbinding sites but not at GR-exclusive sites. All three NeuroD transcription factors acted as DNA-binding-dependent coactivators for bothMR and GR in reporter assays in heterologous HEK293 cells, likely via indirect interactions with the receptors. In conclusion, a NeuroD familymemberbinding to an additionalmotif near theGRE seems to drive specificity forMRoverGRbindingat hippocampalbindingsites.