Understanding the reorganization of neural circuits spared after spinal cord injury in the motor cortex and spinal cord would provide insight for developing therapeutics. Using optogenetic mapping we demonstrate a transhemispheric recruitment of neural circuits in the contralateral cortical M1/M2 area to improve the impaired forelimb function after a cervical 5 right-sided hemisection in mice, a model mimicking the human Brown-Séquard syndrome. This cortical reorganization can be elicited by a selective cortical optogenetic neuromodulation paradigm. Areas of whisker, jaw, and neck, together with the rostral forelimb area, on the motor cortex ipsilateral to the lesion are engaged to control the ipsilesional forelimb in both stimulation and non-stimulation groups at 8 weeks post-injury. However, significant functional benefits are only seen in the stimulation group. Using anterograde tracer, we further reveal a robust sprouting of the intact corticospinal tract in the spinal cord of those animals receiving optogenetic stimulation. The intraspinal cortical spinal axonal sprouting corelates with the forelimb functional recovery. Thus, specific neuromodulation of the cortical neural circuits induces massive neural reorganization both in the motor cortex and spinal cord, constructing an alternative motor pathway in restoring impaired forelimb function.
Wei Wu, Tyler Nguyen, Josue D. Ordaz, Yi Ping Zhang, Nai-Kui Liu, Xinhua Hu, Yuxiang Liu, Xingjie Ping, Qi Han, Xiangbing Wu, Wenrui Qu, Sujuan Gao, Christopher B. Shields, Xiaoming Jin, Xiao-Ming Xu