Comparative anatomy of the dentate mossy cells in non-human primates: their spatial distributions and axonal projections compared with mouse mossy cells

Glutamatergic mossy cells (MCs) mediate associational and commissural connectivity, exhibiting significant heterogeneity along the septotemporal axis of the mouse dentate gyrus (DG). However, it remains unclear whether the neuronal features of MCs are conserved across mammals. This study compares the neuroanatomy of MCs in the DG of mice and monkeys. The MC marker, calretinin, distinguishes two subpopulations: septal and temporal. Dual-colored fluorescence labeling is utilized to compare the axonal projection patterns of these subpopulations. In both mice and monkeys, septal and temporal MCs project axons across the longitudinal axis of the ipsilateral DG, indicating conserved associational projections. However, unlike in mice, no MC subpopulations in monkeys make commissural projections to the contralateral DG. In monkeys, temporal MCs send associational fibers exclusively to the inner molecular layer, while septal MCs give rise to wide axonal projections spanning multiple molecular layers, akin to equivalent MC subpopulations in mice. Despite conserved septotemporal heterogeneity, interspecies differences are observed in the topological organization of septal MCs, particularly in the relative axonal density in each molecular layer along the septotemporal axis of the DG. In summary, this comparative analysis sheds light on both conserved and divergent features of MCs in the DG of mice and monkeys. These findings have implications for understanding functional differentiation along the septotemporal axis of the DG and contribute to our knowledge of the anatomical evolution of the DG circuit in mammals.Significance StatementThis study investigates glutamatergic mossy cells (MCs) in the dentate gyrus (DG) of mice and monkeys, revealing both conserved and species-specific features. While associational projections are consistent across species, monkeys lack the commissural projections of MCs seen in mice. Additionally, the topological organization of septal MC axons differs, particularly in relative axonal density along the septotemporal axis. These findings provide insights into the anatomical evolution of the DG circuit in mammals, shedding light on potential functional distinctions. The study enhances our understanding of neural circuitry, offering a platform for further exploration into the intricate relationship between structure and function in the mammalian brain