Hippocampal gene expression in zebra finches reveals sex- and subregion-specific topographies

The hippocampus is a highly evolutionarily conserved brain region that supports spatial memory, stress responses, and social behavior across vertebrates. While mammalian hippocampal transcriptomics have been extensively characterized, comparative data from the avian hippocampus remain limited. Using RNA sequencing, we characterized hippocampal gene expression in zebra finches ( Taeniopygia guttata ) across sex, rostral-caudal subregions, and acute social conditions (Paired, Separated, Unpaired). Although acute social conditions produced only modest transcriptional effects, with 32 differentially expressed genes (DEGs) reaching significance, robust differential gene expression emerged across sex (2,148 DEGs) and rostral-caudal subregion (2,259 DEGs). Notably, 28% of sex-biased DEGs mapped to the Z chromosome, consistent with incomplete dosage compensation in the avian brain. Gene ontology enrichment across sex highlighted SMAD signaling and transforming growth factor beta (TGF-β)/activin pathway regulation as repeated organizational features of the zebra finch hippocampal transcriptome. Region-specific DEGs converged on themes of membrane excitability and synaptic plasticity, while social-condition effects were sex- and subregion-specific, with females demonstrating a more pronounced transcriptional response to pair bonding and mate separation than males, particularly in the caudal hippocampus. These findings establish a foundational molecular reference for the zebra finch hippocampus and position the songbird as a comparative model for investigating how sex, neuroanatomical subregion, and social context interact at the molecular level to shape hippocampal function across vertebrates. Significance Statement The hippocampus plays a central role in memory, spatial navigation, and social behavior across vertebrates, yet comparative transcriptomic data from the avian hippocampus remain limited. Using RNA sequencing in zebra finches, we demonstrate that sex and rostral-caudal subregion are dominant predictors of hippocampal gene expression, outweighing the effects of social condition. Strong enrichment of Z-linked genes among sex-biased transcripts highlights incomplete dosage compensation as a key contributor to molecular sex differences in the avian brain. Social condition effects were sex- and subregion-specific, with females showing robust transcriptional responses to pair bonding and separation across subregions. These findings establish a foundational molecular reference for the songbird hippocampus and advance understanding of how sex- and region-specific gene expression may shape hippocampal function.