Very-light-intensity exercise as minimal intensity threshold for activating dorsal hippocampal neurons: Evidence from rat physiological exercise model

Exercise benefits the brain, particularly the learning and memory center—the dorsal hippocampus (dHPC)—and holds promise for therapeutic applications addressing age-related cognitive deficits. While moderate-to-vigorous-intensity exercise is commonly recommended for health benefits, our translational research proposes the effectiveness of very-light-intensity exercise in enhancing cognitive functions. However, the intensity-dependent characteristics of HPC activation have yet to be fully delineated; therefore, there is no evidence of whether such easily accessible exercises for people of all ages and most fitness levels can activate HPC neurons. Here, we aimed to clarify this question using a physiologically sound rat exercise model. We used a previously established rat treadmill running model within a metabolic chamber and measured maximal oxygen uptake ($\dot{V}{O}_{2\max }$) during an incremental running test. Referring to the American College of Sports Medicine's $\dot{V}{O}_{2\max }$-based intensity classification, rats were assigned to one of five groups: resting control, very-light, light, moderate, and vigorous exercise intensity. We immunohistochemically assessed the effects of a single bout of exercise on dHPC neuronal activity and measured $\dot{V}{O}_2$ and blood lactate as exercise intensity indicators. dHPC neuronal activity increased with exercise intensity, even at light-intensity without blood lactate accumulation, and correlated positively with increasing $\dot{V}{O}_2$. The dorsal dentate gyrus and CA1 sub-regions were markedly activated even by very-light-intensity exercise. Our findings demonstrate the intensity-dependent activation of dHPC neurons, with very-light-intensity exercise as the minimal intensity threshold. These strongly support our hypothesis that very-light-intensity exercise serves as a viable memory-enhancing strategy, beneficial for various populations including low-fitness individuals and the elderly.