Damage to the hippocampal formation results in profound impairments in spatial navigation in rats and mice leading to the widely accepted assumption that the hippocampal cellular and molecular memory mechanisms of both genera are conserved. Recently our group has shown in two rat strains that hippocampal-dependent training in the water maze specifically induces robust ‘sprouting’ of granule cell suprapyramidal mossy fiber axon terminal fields. Here we sought to investigate whether the pronounced remodeling of adult hippocampal circuitry observed in the rat is also present in the mouse motivated by the thought that subsequent studies using genetically-engineered mice could then be implemented to explore the molecular mechanisms underlying training-dependent axonal growth in adult rodents. However, in contrast to Wistar rats, no changes in the Timm's-stained area of mossy fiber terminal fields (MFTFs) were observed in C57BL/6J or 129Sv/EmsJ inbred wild-type mice after water maze training. Neither extending the duration of training nor scaling down the size of the apparatus was able to induce sprouting in mouse mossy fiber pathways. Though there may be similarities in the ultimate output of the hippocampus of rats and mice as inferred from lesion studies, the current results, as well as differences in learning and memory characteristics between the two genera, suggest that the way in which the component circuitry functions is likely to be different; a not too surprising conclusion given the substantial evolutionary distance between them (>20 million years). The present findings afford an opportunity for uncovering linkages between evolutionarily significant alterations in hippocampal circuitry in relation to genera-specific information storage requirements.