Induction of c-Fos, Zif268, and Arc from acute bouts of voluntary wheel running in new and pre-existing adult mouse hippocampal granule neurons

The functional significance of newly formed granule neurons in the adult mammalian hippocampus remains a mystery. Recently, it was demonstrated that wheel running increases new neuron survival and c-Fos expression in new and pre-existing granule cells in an activity-dependent manner. It is currently unknown whether other immediate early genes (IEGs) become expressed in granule neurons from running. Further, it is unknown whether locomotor activity in home cages without wheels can influence neurogenesis and IEG expression similar to running. The purpose of this study was three-fold: (1) to determine if Arc and Zif268 expression are also induced from wheel running in both pre-existing and newly formed neurons (2) to determine if neurogenesis and IEG induction is related to horizontal distance traveled in home cages without wheels, and (3) to determine whether IEG induction is related to acute bouts of running or chronic effects. Adult C57BL/6J female mice were placed in cages with or without running wheels for 31 days. The first 10 days, mice received daily injections of 5-Bromo-2′-deoxyuridine (BrdU) to label dividing cells. On day 1, running and non-running animals were euthanized either 2 h after peak activity, or during a period of relative inactivity. Immunohistochemistry was performed on hippocampal sections with antibodies against BrdU, mature neuron marker NeuN, c-Fos, Arc, and Zif268. Results demonstrate that Arc, Zif268, and c-Fos are induced from wheel running but not movement in cages without wheels. All IEGs were expressed in new neurons from running. Further, IEGs were induced acutely by running, as increased expression did not continue into the light cycle, a period of relative inactivity. The results suggest that robust movements, like running, are necessary to stimulate IEG expression and neurogenesis. Moreover, results suggest new neurons from running may be processing information about running behavior itself.

▶Arc, Zif268, and c-Fos protein become induced in the dentate gyrus from running. ▶Arc, Zif268, and c-Fos are not induced in the dentate from movements in home cages. ▶Arc, Zif268, and c-Fos are preferentially induced in new neurons from running. ▶Neurogenesis is related to distance traveled on running wheels, but not in home cages. ▶Immediate early gene activity is acutely induced from running.