Running enhances neurogenesis, learning, and long-term potentiation in mice

Abstract

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.

Figure 1

Flowchart of the experiment. Controls were housed in standard 30- by 18-cm cages, whereas runners had 48- by 26-cm housing with free access to a running wheel (1). Mice in both conditions received BrdU (50 μg/g per day) injections for the first 10 days after their housing assignment. After 1 month in their respective environments, mice were tested in the water maze (2) between days 30 and 36 or between days 43 and 49. Mice were anesthetized and decapitated between days 54 and 118; one hemisphere was used for electrophysiology; the other was used for immunocytochemistry (3).

Figure 2

Water maze learning in controls and runners trained with two trials per day (four-trial data are not shown here, but see description in Results). Mice were trained over 6 days to find the hidden platform in the Morris water maze. A significant difference developed between the groups (P < 0.04) in path length (a) and (P < 0.047) in latency (b). Results of probe test 4 hr after the last trial on day 6 (c).

Figure 3

LTP in dentate gyrus (a) and area CA1 (b). (a1, b1) Digital images of hippocampal slices showing the position of the stimulation and recording electrodes. (a2, b2) Paired-pulse facilitation at 50-, 100-, 200-, and 500-ms interpulse intervals. EPSP, excitatory postsynaptic potential. There was no difference between slices from controls and runners (P > 0.91). (a3, b3) Time course of LTP in slices from controls (▵) and runners (●) . In addition, representative examples are shown of evoked responses immediately before (Pre) and 30 min after (Post) induction of LTP. Example waveforms are the average of 20 responses recorded over a 5-min period. Population spikes were apparent in some animals in each group after LTP induction. (Scale bars under a1 and b1 indicate 250 μm.)

Figure 4

Confocal images of BrdU-positive cells in control (A) and runner coronal sections (B). Sections were immunofluorescent triple-labeled for BrdU (red), NeuN, indicating neuronal phenotype (green), and S100β, selective for glial phenotype (blue). (Scale bar indicates 50 μm.)