Light-exercise-induced dopaminergic and noradrenergic stimulation in the dorsal hippocampus: using a rodent physiological exercise model

Abstract

AbstractGrowing evidence shows that exercise acts on the dorsal hippocampus and promotes the learning process and memory formation. For decades, these beneficial effects of exercise have been based on a lot of research using demanding and stress-response-inducing exercise at moderate-to-vigorous intensities. In contrast, our translational research with animals and humans has focused on light exercise, which almost anyone can safely perform with minimal stress. Using our special exercise model, which is based on physiological responses such as lactate threshold (LT), we found that even light exercise can boost dorsal hippocampal activity and enhance memory performance. Although the circuit mechanism underlying this boost remains unclear, arousal promotion even with light-intensity exercise implies the involvement of the monoaminergic ascending arousal system, which is crucial for memory enhancement. We thus aimed to examine this hypothesis using our physiological exercise model based on the LT of rats. First, we immunohistochemically assessed the neuronal activation of the dorsal hippocampal sub-regions, as well as tyrosine hydroxylase-positive (TH+) neurons and serotonin-positive (5-HT+) neurons in the brainstem monoaminergic nuclei. Second, we monitored the dynamics of monoamine release at the dorsal hippocampus usingin vivomicrodialysis combined with the high-performance liquid chromatography (HPLC) system. We found that even light exercise increased neuronal activity in the dorsal hippocampal sub-regions and induced the release of noradrenaline (NA) and dopamine (DA). Additionally, we found that TH+neurons in the locus coeruleus (LC) and the ventral tegmental area (VTA) were activated even by light exercise and were both positively correlated with the dorsal hippocampal activation. Meanwhile, the serotonergic system was not affected by exercise. Overall, these results suggest that light exercise stimulates the dorsal hippocampal neurons probably through the noradrenergic neurons in the LC and dopaminergic neurons in the VTA. Our findings provide insight into the underlying circuit mechanisms of light-exercise-enhanced memory.Graphical abstractCONCLUSIONLight exercise could activate the dorsal hippocampus through LC-NA and VTA-DA stimulation.Our previous research with both animals and humans has demonstrated that even light exercise below the lactate threshold (or 50% VO2peak) can boost neuronal activity in the dorsal hippocampus and enhance learning and memory. While accumulating evidence highlights the significance of cellular and molecular basis of exercise benefits, the basic circuit mechanism underlying this boost remains largely undetermined. It has been proposed that exercise engages the ascending monoaminergic projections, which facilitates dorsal hippocampus-associated functions. Thus, we examined this hypothesis using our animal exercise model, and found a possible contribution of noradrenergic neurons in the locus coeruleus and dopaminergic neurons in the ventral tegmental area to dorsal hippocampal activation during light exercise, implying a circuit mechanism for light-exercise-induced benefits to the dorsal hippocampus.