Light‐exercise‐induced dopaminergic and noradrenergic stimulation in the dorsal hippocampus: Using a rat physiological exercise model

Exercise activates the dorsal hippocampus that triggers synaptic and cellar plasticity and ultimately promotes memory formation. For decades, these benefits have been explored 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-intensity exercise (light exercise) below the lactate threshold (LT), which almost anyone can safely perform with minimal stress. We found that even light exercise can stimulate hippocampal activity and enhance memory performance. Although the circuit mechanism of this boost remains unclear, arousal promotion even with light exercise implies the involvement of the ascending monoaminergic system that is essential to modulate hippocampal activity and impact memory. To test this hypothesis, we employed our physiological exercise model based on the LT of rats and immunohistochemically assessed the neuronal activation of the dorsal hippocampal sub-regions and brainstem monoaminergic neurons. Also, we monitored the extracellular concentration of monoamines in the dorsal hippocampus using in vivo microdialysis. We found that even light exercise increased neuronal activity in the dorsal hippocampal sub-regions and elevated the extracellular concentrations of noradrenaline and dopamine. Furthermore, we found that tyrosine hydroxylase-positive 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. In conclusion, our findings demonstrate that light exercise stimulates dorsal hippocampal neurons, which are associated with LC-noradrenergic and VTA-dopaminergic activation. This shed light on the circuit mechanisms responsible for hippocampal neural activation during exercise, consequently enhancing memory function.