Rotarod training in mice is associated with changes in brain structure observable with multimodal MRI

The brain has been shown to remain structurally plastic even throughout adulthood. However, little is known how motor-skill training affects different MRI modalities in the adult mouse brain. The aim of this study is to investigate whether rotarod training, a simple motor training task taken from the standard test battery, is associated with structural plasticity observable with different MRI modalities in adult C57BL/6 mice. The rotarod is a standard test that taxes motor coordination and balance. We use T2-weighted MRI followed by deformation-based morphometry to assess local volume and fractional anisotropy (FA) derived from diffusion MRI to assess microstructure ex-vivo. Using deformation-based morphometry we found that the hippocampus, frontal cortex and amygdala are larger in rotarod-trained mice compared to untrained controls. Surprisingly, the cerebellum and white matter in the corpus callosum underlying the primary motor cortex are smaller after training. We also found that the volume of the motor cortex is positively correlated with better rotarod performance. Diffusion imaging indicates group differences and behavioral correlations with FA, a measure of microstructure. Trained mice have higher FA in the hippocampus. Better rotarod performance is associated with higher FA in the hippocampus and lower FA in the primary visual cortex. This is the first study to reveal the substantial structural reorganization of the adult mouse brain following only a relatively brief period of motor-skill training by using complementary measures of microstructure and volume.