Exercise in developing rats promotes plasticity in the prefrontal cortex: behavioral and neurobiological indications

Physical exercise has repeatedly been shown to trigger positive effects on brain function including improved learning, memory, and executive functions. In addition, corresponding physiological changes have been observed, such as increased neurotrophic factors, changes in neurotransmitter concentrations, and increased dendritic spines. However, these changes have not been well described outside of the hippocampus, including the medial prefrontal cortex (mPFC), and have not been directly compared at different points of development. Because the prefrontal cortex is one of the last brain areas to fully mature, considering the age at which intervention, such as exercise, takes place is particularly important. Additionally, in human studies the data suggest that exercise has the most profound effects on prefrontal-mediated cognitive functions, while there is considerably less evidence on how exercise affects these functions in animals. The experiments presented here draw upon several well-established methodologies to explore the behavioral and physiological changes due to exercise that take place during adulthood compared to adolescence, as well as the role of mPFC sub regions in instrumental extinction and renewal. To that end, these experiments employ conditioning paradigms using appetitive lever-pressing to assess renewal of extinguished instrumental responding following exercise or pharmacological manipulations. Additionally, because there are multiple reports suggesting that early experiences can affect prefrontal neuronal morphology, dendritic length, complexity, and spine density was examined in young or adult male rats that had access to a locked (no exercise) or unlocked (exercise) running wheel for two weeks. Furthermore, norepinephrine transporter (NET) protein expression in the mPFC was examined by Western blot. Collectively, these experiments suggest that exercise in developing, but not adult rats, reduces the expression of instrumental renewal. The precise role of the mPFC and its sub-regions (i.e., prelimbic (PL) and infralimbic (IL)) in instrumental renewal was examined, providing evidence that the behavioral consequences of physical exercise may be due to modifications not only restricted to the mPFC, but also that exercise may have preferential effects on sub-regions, or change the balance of activation. The finding that when juvenile rats exercised they showed less ABA renewal than non-exercisers, paired with the reduction of ABA renewal when the PL was inactivated (and indeed, almost an identical reduction in the two experiments) points to the deduction that exercise is affecting the PL, perhaps more so than the IL or other mPFC regions.