Exercise type-brain region interactions determine the effects of exercise on the hippocampus.

Introduction: Exercise enhances hippocampal function, which is critical for learning, memory, and dementia prevention. However, the effects of exercise depend not only on intensity and frequency but also on the type of exercise, and not all exercise paradigms reliably activate hippocampal circuits. Methods: We compared treadmill exercise (TE) and rotarod exercise (RE) in mice to determine whether exercise type differentially influences neural activity and hippocampal plasticity across brain regions, using acute and chronic exercise paradigms. Results: In acute exercise experiments, TE robustly increased neuronal activation in the dorsal hippocampus and entorhinal cortex. In contrast, RE activated other brain regions, including the ventral hippocampus and dorsal raphe nucleus, but did not increase activity in the dorsal hippocampus-entorhinal pathway. In chronic phase experiments, both TE and RE produced antidepressant effects, whereas only TE stimulated hippocampal neurogenesis. Discussion: These results demonstrate that the effects of exercise on the brain are determined by interactions between exercise type and brain region. The findings highlight region-specific and exercise type-dependent characteristics of exercise-induced brain plasticity, underscoring the importance of considering exercise type when aiming to promote hippocampal health and prevent dementia.