Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning.
New neurons are added continuously to certain areas of the adult brain, such as the hippocampus and olfactory bulb (1, 2). The functional significance of new hippocampal cells is not clear. In birds, food storage and retrieval experience correlate with changes in hippocampal size and neurogenesis (3). In mice, neurogenesis in the dentate gyrus increases with exposure to an enriched environment, and it is associated with improved learning (4). Similarly, voluntary physical activity in a running wheel enhances the number of new hippocampal cells (5). Although it is not known whether running also affects learning, it has been shown that physical activity facilitates recovery from injury (6) and improves cognitive function (7). Furthermore, trophic factors, associated with progenitor cell survival and differentiation (8), alterations in synaptic strength (9), long-term potentiation (LTP) (10), and memory function (11), are elevated after exercise (12, 13). At the cellular level, wheel running enhances the firing rate of hippocampal cells in a manner that correlates with running velocity (14). Thus, exercise may increase synaptic plasticity and learning, as well as neurogenesis. We designed the following experiments to test this hypothesis.