Long-Term Exercise Is a Potent Trigger for ΔFosB Induction in the Hippocampus along the dorso-ventral Axis

Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor Delta FosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces Delta FosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso-ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/Delta FosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/Delta FosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/Delta FosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/Delta FosB immunoreactivity was primarily due to increased Delta FosB. These results suggest that long-term physical exercise is a potent trigger for Delta FosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/Delta FosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which Delta FosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that Delta FosB is a new molecular target involved in regulating exercise-induced hippocampal plasticity.