Treadmill Exercise Regulates Synaptic Plasticity In The Motor Cortex Via MTOR Pathway

Numerous studies have demonstrated that physical exercise reduces the risk of mental illness and improves learning and memory.Although previous findings supported that exercise can regulate synaptic plasticity and learning memory via multiple pathways,little in vivo evidence has been provided to illustrate the regulation of synaptic plasticity in exercise.Our previous research demonstrated that treadmill exercise suppressed stress-induced dendritic spine elimination in mouse barrel cortex and improved working memory via BDNF/Trk B pathway.Here we further investigated the downstream signaling pathway of BDNF in mediating exercise-improved synaptic plasticity in mouse motor cortex.By performing chronic treadmill exercise in combined with two-photon in vivo imaging,we found that exercise training increases dendritic spine formation,enhance cortical neuronal activity and activates the mammalian target of rapamycin(mTOR) pathway in mouse motor cortex,in addition to the improvement of the acquisition of complex motor skills.Using pharmaceutical inhibition of mTOR signaling pathway by rapamycin,the exercise-mediated dendritic spine formation and learning improvements were totally abolished.Our studies collectively suggest that exercise can improve cortical synaptic plasticity and learning memory via mTOR pathway activation.This mTOR-mediated synaptic plasticity regulation mechanism facilitates the understanding of how exercise improves cognitive functions,and also provides new insights for clinical intervention of cognitive deficits by exercise training.