Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6J mice.

Previous studies have shown that housing mice with toys and running wheels increases adult hippocampal neurogenesis and enhances performance on the water maze. However, the relative contribution of running versus enrichment to the neurogenic and pro-cognitive effects is not clear. Recently, it was demonstrated that enrichment devoid of running wheels does not significantly enhance adult hippocampal neurogenesis in female C57BL/6J mice. However, novel toys were not rotated into the cages, and dietary enrichment was not included, so it could be argued that the environment was not enriched enough. In addition, only females were studied, and animals were group-housed, making it impossible to record individual running behavior or to determine the time spent running versus exploring the toys. Therefore, we repeated the study in singly housed male C57BL/6J mice and enhanced enrichment by rotating novel tactile, visual, dietary, auditory, and vestibular stimuli into the cages. Mice were housed for 32 days in one of four groups: running-only, enrichment-only, running plus enrichment, and standard cage. The first 10 days bromodeoxyuridine (BrdU) was administered to label dividing cells. The last 5 days mice were tested on the water maze, and then euthanized to measure number of BrdU cells co-labeled with neuronal nuclear marker (NeuN) in the dentate gyrus. Mice in the running-only group ran, on average, equivalent distances as animals in the running plus enrichment group. The combination of enrichment and running did not significantly increase hippocampal neurogenesis any more than running alone did. Animals in the running-only condition were the only group to show enhanced acquisition on water maze relative to standard cage controls. We confirm and extend the conclusion that environmental enrichment alone does not significantly increase hippocampal neurogenesis or bestow spatial learning benefits in male C57BL/6J mice, even when the modalities of enrichment are very broad.