Corticospinal circuit neuroplasticity may involve silent synapses: Implications for functional recovery facilitated by neuromodulation after spinal cord injury

Mingcong Chen; Zuxin Chen; Xiao Xiao; Libing Zhou; Rao Fu; Xian Jiang; Mao Pang; Jianxun Xia

doi:10.1016/j.ibneur.2022.08.005

Corticospinal circuit neuroplasticity may involve silent synapses: Implications for functional recovery facilitated by neuromodulation after spinal cord injury

IBRO Neurosci Rep. 2022 Aug 18:14:185-194. doi: 10.1016/j.ibneur.2022.08.005. eCollection 2023 Jun.

Authors

Mingcong Chen¹, Zuxin Chen², Xiao Xiao³, Libing Zhou⁴, Rao Fu⁵, Xian Jiang⁶, Mao Pang⁷, Jianxun Xia⁸

Affiliations

¹ Department of Orthopedics and Traumatology, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, China.
² Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS); Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong 518055, China.
³ Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education; Behavioral and Cognitive Neuroscience Center, Institute of Science and Technology for Brain-Inspired Intelligence; MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
⁴ Guangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University)-Ministry of Education, Guangzhou, Guangdong 510632, China.
⁵ Department of Anatomy, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong 518100, China.
⁶ Institute of Neurological and Psychiatric Disorder, Shenzhen Bay laboratory, Shenzhen, Guangdong 518000, China.
⁷ Department of Spine Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou, Guangdong 510630, China.
⁸ Department of Basic Medical Sciences, Yunkang School of Medicine and Health, Nanfang College, Guangzhou, Guangdong 510970, China.

Abstract

Spinal cord injury (SCI) leads to devastating physical consequences, such as severe sensorimotor dysfunction even lifetime disability, by damaging the corticospinal system. The conventional opinion that SCI is intractable due to the poor regeneration of neurons in the adult central nervous system (CNS) needs to be revisited as the CNS is capable of considerable plasticity, which underlie recovery from neural injury. Substantial spontaneous neuroplasticity has been demonstrated in the corticospinal motor circuitry following SCI. Some of these plastic changes appear to be beneficial while others are detrimental toward locomotor function recovery after SCI. The beneficial corticospinal plasticity in the spared corticospinal circuits can be harnessed therapeutically by multiple contemporary neuromodulatory approaches, especially the electrical stimulation-based modalities, in an activity-dependent manner to improve functional outcomes in post-SCI rehabilitation. Silent synapse generation and unsilencing contribute to profound neuroplasticity that is implicated in a variety of neurological disorders, thus they may be involved in the corticospinal motor circuit neuroplasticity following SCI. Exploring the underlying mechanisms of silent synapse-mediated neuroplasticity in the corticospinal motor circuitry that may be exploited by neuromodulation will inform a novel direction for optimizing therapeutic repair strategies and rehabilitative interventions in SCI patients.

Keywords: AMPARs, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; BDNF, brain-derived neurotrophic factor; BMIs, brain-machine interfaces; CPG, central pattern generator; CST, corticospinal tract; Corticospinal motor circuitry; DBS, deep brain stimulation; ESS, epidural spinal stimulation; MEPs, motor-evoked potentials; NHPs, non-human primates; NMDARs, N-methyl-d-aspartate receptors; Neuromodulation; Neuroplasticity; PSNs, propriospinal neurons; Rehabilitation; SCI, spinal cord injury; STDP, spike timing-dependent plasticity; Silent synapses; Spinal cord injury; TBS, theta burst stimulation; TMS, transcranial magnetic stimulation; TrkB, tropomyosin-related kinase B; cTBS, continuous TBS; iTBS, intermittent TBS; mTOR, mammalian target of rapamycin; rTMS, repetitive TMS; tDCS, transcranial direct current stimulation; tcSCS, transcutaneous spinal cord stimulation.