Exercise for brain health: From cells to circuits

Exercise has been central to human brain evolution. Genus Homo was a nomadic species that constantly explored novel environments, which requires the encoding of new spatial and contextual patterns and the consolidation and recall of details to localize potential food and avoid danger, functions associated with the hippocampus. Interestingly, no primates other than humans run long distances over extended periods using aerobic metabolism, a capacity described as endurance running (ER). It has been hypothesized that ER capacity may have had relevant effects on the evolution of brain structure and cognition in the genus Homo. Paradoxically, modern humans have become sedentary and no longer need to run for food or survival. The lack of exercise in the population has increased the risk of brain disorders. Studies in human and animal models show that exercise elicits functional and structural changes throughout the brain, which may serve as a mechanism to counteract the changes induced by aging and reduced physical activity. Here, we describe the cortico-hippocampal circuitry and summarize evidence from human and animal models of aging-induced and exercise-induced changes in cortical and subcortical areas that provide polymodal information and modulatory inputs to the hippocampus, respectively. We discuss how exercise-induced plasticity in the cortico-hippocampal circuit may improve brain health.