Voluntary running-enhanced synaptic plasticity, learning and memory are mediated by Notch1 signal pathway in C57BL mice.

It is well known that voluntary running can enhance synaptic plasticity and improve learning and memory abilities. The Notch1 receptor is also reported to be associated with these processes, but its role in running-induced alterations is unclear. In this study, we aimed to investigate whether the Notch1 signalling pathway was involved in voluntary running-induced enhancement of synaptic plasticity, learning and memory. Notch1 heterozygous deficient (Notch1+/-) mice and wildtype (WT) C57BL littermates were randomly divided into runner group and non-runner group. Mice were given free access to running wheels for 14 days in both the Notch1+/- runner group and the WT runner group. Our results demonstrate that Notch1 knockdown impairs the performance in the novel object recognition (NOR) test and Morris water maze test and decreases the synaptic plasticity. Voluntary running improves spatial learning and memory abilities, promotes synaptic plasticity and increases expressions of postsynaptic proteins in WT mice but not in Notch1+/- mice. Our results suggest that Notch1 plays a vital role in spatial learning and memory, synaptic plasticity under normal physiological conditions and voluntary running conditions. These findings will set the groundwork and fill in some gaps for understanding the role of Notch1 signalling in voluntary running-induced phenomena.