Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI
成果类型：
Article
署名作者：
Stachowski, Nicholas J.; Wheel, Jaimena H.; Singh, Shayna; Atoche, Sebastian J.; Yao, Lihua; Garcia-Ramirez, D. Leonardo; Giszter, Simon F.; Dougherty, Kimberly J.
署名单位：
Drexel University
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-12717
DOI：
10.1073/pnas.2406333122
发表日期：
2025-04-15
关键词：
epidural electrical-stimulation
cord-injury
presynaptic inhibition
locomotor recovery
neurotrophic factor
dorsal-horn
electrophysiological features
motor function
trkb protein
bdnf
摘要：
Various strategies targeting spinal locomotor circuitry have been associated with functional improvements after spinal cord injury (SCI). However, the neuronal populations mediating beneficial effects remain largely unknown. Using a combination therapy in a mouse model of complete SCI, we show that virally delivered brain-derived neurotrophic factor (BDNF) (AAV-BDNF) activates hindlimb stepping and causes hyperreflexia, whereas submotor threshold epidural stimulation (ES) reduces BDNF-induced hyperreflexia. Given their role in gating proprioceptive afferents and as a potential convergence point of BDNF and ES, we hypothesized that an enhanced excitability of inhibitory ROR(3 neurons would be associated with locomotor improvements. Ex vivo spinal slice recordings from mice with a range of locomotor and hyperreflexia scores revealed that the excitability of ROR(3 neurons was related to functional outcome post-SCI. Mice with poor locomotor function after SCI had less excitable ROR(3 neurons, but the excitability of ROR(3 neurons was similar between the uninjured and best stepping SCI groups. Further, chemogenetic activation of ROR(3 neurons reduced BDNF-induced hyperreflexia and improved stepping, similar to ES. Our findings identify inhibitory ROR(3 neurons as a target population to limit hyperreflexia and enhance locomotor function after SCI.