Dual electrical stimulation at spinal-muscular interface reconstructs spinal sensorimotor circuits after spinal cord injury

• Published in: Nature communications Vol. 15; no. 1; p. 619
• Main Authors: Zhou, Kai, Wei, Wei, Yang, Dan, Zhang, Hui, Yang, Wei, Zhang, Yunpeng, Nie, Yingnan, Hao, Mingming, Wang, Pengcheng, Ruan, Hang, Zhang, Ting, Wang, Shouyan, Liu, Yaobo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 14/19; 38/77; 38/91; 59/57; 631/378/1687/1825; 631/378/2632/1823; 631/378/3920; 631/61; 639/166/985; 64/60; 9/10; 9/30; Circuits; Electric Stimulation; Electrical stimuli; Epidural; Excitability; Humanities and Social Sciences; Humans; Motor Neurons; multidisciplinary; Muscles; Neural networks; Neuromodulation; Parameters; Regeneration; Science; Science (multidisciplinary); Sensorimotor system; Spinal Cord - physiology; Spinal cord injuries; Spinal Cord Injuries - therapy; Stimulation; Structure-function relationships
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-44898-9

The neural signals produced by varying electrical stimulation parameters lead to characteristic neural circuit responses. However, the characteristics of neural circuits reconstructed by electrical signals remain poorly understood, which greatly limits the application of such electrical neuromodulation techniques for the treatment of spinal cord injury. Here, we develop a dual electrical stimulation system that combines epidural electrical and muscle stimulation to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. We demonstrate that a stimulus frequency of 10−20 Hz under dual stimulation conditions is required for structural and functional reconstruction of spinal sensorimotor circuits, which not only activates genes associated with axonal regeneration of motoneurons, but also improves the excitability of spinal neurons. Overall, the results provide insights into neural signal decoding during spinal sensorimotor circuit reconstruction, suggesting that the combination of epidural electrical and muscle stimulation is a promising method for the treatment of spinal cord injury. Electrical signals with characteristic parameters for reconstructing neural circuits remain incompletely understood, limiting the therapeutic potential of electrical neuromodulation techniques. Here, the authors demonstrate that dual electrical stimulation at 10–20 Hz rebuilds the spinal sensorimotor neural circuit after spinal cord injury, indicating the characteristic signals of circuit remodeling.