Abstract Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF). Keywords: Adult neurogenesis, Dentate gyrus, Running, Learning and memory, Neurotrophic factors, Synaptic plasticity, Endurance factors

7 Conclusions While previous studies suggested that both EE and exercise increase adult neurogenesis, recent research has shown only exercise enhances the production of new DG neurons. The positive effects of exercise are likely the result of a combination of factors including, but not limited to enhanced neurogenesis, modifications in synaptic plasticity, spine density, neurotrophins, and angiogenesis that may mediate the beneficial effects on learning and memory, reduction of the risk of neurodegenerative diseases and delay age-related cognitive decline. Within the hippocampus, the most pronounced changes with physical activity are in the DG subfield, with an increased production of new neurons and BDNF levels, which are associated with improved performance on tasks presumably mediated by the DG. Furthermore, running, but not antidepressants that block serotonergic or noradrenergic reuptake, triggers the production of new neurons in the DG. However, we also suggest that caution should be used when applying exercise to conditions of brain injury and neurodegenerative disease as the consequences could be detrimental as found in a mouse model of Huntington's disease. While further research is needed to understand the cellular mechanisms underlying effects of aerobic activity on the brain, exercise is a powerful lifestyle intervention that could be used to augment and maintain cognitive function throughout the lifespan.