Differential effects of treadmill running and wheel running on spatial or aversive learning and memory: roles of amygdalar brain-derived neurotrophic factor and synaptotagmin I.

Chronic exercise has been reported to improve cognitive function. However, whether and how different types of exercise affect various learning and memory tasks remain uncertain. To address this issue, male BALB/c mice were trained for 4 weeks under two different exercise protocols: moderate treadmill running or voluntary wheel running. After exercise training, their spatial memory and aversive memory were evaluated by a Morris water maze and by one-trial passive avoidance (PA), respectively. Levels of neural plasticity-related proteins, i.e. brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and synaptotagmin I (Syt I), in hippocampus and amygdala were determined by ELISA or immunoblotting. Finally, the functional roles of these proteins in the basolateral amygdala were verified by locally blocking them with K252a (a TrkB kinase inhibitor), or lentivirus expressing Syt I shRNA. We found that (1) although both moderate treadmill running and wheel running improved the Morris water maze performance, only the former improved PA performance; (2) likewise, both exercise protocols upregulated the BDNF-TrkB pathway and Syt I in the hippocampus, whereas only treadmill exercise upregulated their expression levels in the amygdala; (3) local injection of K252a abolished the treadmill exercise-facilitated PA performance and upregulation of amygdalar TrkB and Syt I; and (4) local administration of Syt I shRNA abolished the treadmill exercise-facilitated PA performance and upregulation of amygdalar Syt I. Therefore, our results support the notion that different forms of exercise induce neuroplasticity changes in different brain regions, and thus exert diverse effects on various forms of learning and memory.