A History of Exercise Enables Memory Enhancements Induced by Subsequent Exercise

Exercise is known to improve brain function in both humans and non-human animals, particularly on hippocampus-dependent tasks. Unfortunately, exercise only improves memory following a relatively long (2-3 week) period of consistent exercise. One idea is that the brain can be “primed” by previous exposure to exercise so that a much shorter re-exposure to exercise can strengthen cognitive functioning. Previous work has shown that brain-derived neurotrophic factor (BDNF) a protein that may support exercise-induced cognition enhancements, is increased in the hippocampus following a 2-week exercise period.  Importantly, although a short (2d) exercise period alone has no effect on BDNF levels, if combined with a previous history of exercise, a 2-day exercise period now upregulates BDNF in the hippocampus. This suggests that previous exposure to exercise “primes” the brain so that it can respond more efficiently to future exercise. Whether the brain can similarly be primed to support enhanced learning after a brief exercise period is currently unclear. As BDNF is linked with learning and memory, we anticipate that a past history of exercise will prime the brain so that re-exposure to a short 2d exercise period can facilitate long-term memory formation. To test this, we used object location memory (OLM), a sensitive hippocampus-dependent memory task. In OLM, a mouse is exposed to two identical objects during training. During test, one of these objects is moved to a new location. If the mouse remembers the training session, it should prefer the moved object, as mice preferentially explore novelty. Following a 3-minute subthreshold training session, mice normally do not show long-term memory for OLM. Here, three experiments were performed. In the first experiment, mice were given 2 days of exercise only followed by 3-minute threshold OLM training. The second group of mice was given 3 weeks of exercise followed by one week of rest before OLM training. In the third experiment, mice were given 3 weeks of consistent exercise followed by 1 week of rest, and then 2 days of exercise right before training. In each of these experiments, separate groups were tested at 24h, 48h or 72h after training. We found that no long-term memory was formed with just 2 days of exercise (experiment 1) or when 3 weeks of exercise was followed by a week of rest (experiment 2). However, when the three-weeks exercise was paired with another 2 –day exercise bout, animals showed evidence of long-term memory. Specifically, we observed long-term memory at 24h but not at 48 or 72h.  This suggests that the brain can be primed by previous exercise so that even a very short re-exposure to exercise can enhance long-term memory formation.