Anatomical and functional analysis of corticospinal tract in FRDA mouse model

This proposal aims to advance our understanding of the pathophysiology of corticospinal tracts (CST) in FRDA and examines the potential of targeted CST stimulation as a novel therapy. Mouse models are an important tool for investigating the pathogenesis of FRDA and testing the effectiveness of new treatment methods. The main affected neuronal tissues in FRDA are the cerebellum, dorsal root ganglia, spinal cord, and CST. Few studies have focused on CST in FRDA mice, and this proposal aims to fill this knowledge gap. In previous research using a novel mouse model, Dr. Nishiyama showed CST atrophy and impaired motor skills. In this mouse model, frataxin is reduced throughout the body. This does not allow us to tease out the specific contribution of the CST in the pathology, as cerebellar and spinal cord damage may affect motor function, as well as CST. Therefore, Dr. Nishiyama will investigate what changes occur when frataxin is reduced in the CST selectively. She will also investigate whether CST can be a therapeutic target. Brain stimulation through magnetic field generation has been shown to be effective in treating some FRDA symptoms. Dr. Nishiyama hypothesizes that CST activation could also improve symptoms and will use methods to selectively stimulate the CST in FRDA mice and monitor if this treatment is beneficial.