Optogenetic Neuronal Stimulation Promotes Functional Recovery After Spinal Cord Injury

Abstract

Although spinal cord injury (SCI) is the main cause of disability worldwide, there is still no definite and effective treatment method for this condition. Our previous clinical trials confirmed that the increased excitability of the motor cortex was related to the functional prognosis of patients with SCI. However, it remains unclear which cell types in the motor cortex lead to the later functional recovery. Herein, we applied optogenetic technology to selectively activate glutamate neurons in the primary motor cortex and explore whether activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI in rats and the preliminary neural mechanisms involved. Our results showed that the activation of glutamate neurons in the motor cortex could significantly improve the motor function scores in rats, effectively shorten the incubation period of motor evoked potentials and increase motor potentials’ amplitude. In addition, hematoxylin-eosin staining and nerve fiber staining at the injured site showed that accurate activation of the primary motor cortex could effectively promote tissue recovery and neurofilament growth (GAP-43, NF) at the injured site of the spinal cord, while the content of some growth-related proteins (BDNF, NGF) at the injured site increased. These results suggested that selective activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI and may be of great significance for understanding the neural cell mechanism underlying functional recovery induced by motor cortex stimulation.

Genetic control of neuronal activity enhances axonal growth only on permissive substrates

“…In agreement to that, success of these approaches is only significant in incomplete injuries, and greater as more tissue is spared. Incomplete injuries might also help explaining why in our model we did not observe recovery after optogenetic stimulation of the motor cortex while others did (Deng et al 2021), as different spinal injuries were used. Compellingly, compression injury leaves more uninjured tissue and spinal tracts than our injury, that axotomizes all the dorsal tracts, including the main component of the CST in mice.…”

“…Neuronal activity can also alter neuronal metabolism, increasing glycolysis, and lipid synthesis and integration to the membrane, a cellular process essential during axonal extension (Alilain et al 2008 ; Asboth et al 2018 ). Another important cellular component altered by activity is the cytoskeleton and its dynamics, for instance, neuronal activity has been shown to increase dendritic spine microtubule polymerization (Deng et al 2021 ). Accordingly, chemogenetic stimulation increases microtubule dynamics in the distal axonal portion, by reducing tubulin acetylation and increasing tyrosination in this region (Wu et al 2020 ).…”

Genetic control of neuronal activity enhances axonal growth only on permissive substrates

“…In agreement to that, success of these approaches is only significant in incomplete injuries, and greater as more tissue is spared. Incomplete injuries might also help explaining why in our model we did not observe recovery after optogenetic stimulation of the motor cortex while others did [69], as different spinal injuries were used. Compellingly, compression injury leaves more uninjured tissue and spinal tracts than our injury, that axotomizes all the dorsal tracts, including the main component of the CST in mice.…”

A Time-Course Study of the Expression Level of Synaptic Plasticity-Associated Genes in Un-Lesioned Spinal Cord and Brain Areas in a Rat Model of Spinal Cord Injury: A Bioinformatic Approach

“…NMDA is a glutamate receptor and ion channel found in neurons, possibly mediating the increased excitability of the CTX-M. The elective activation of glutamate neurons in the primary CTX-M was related to the functional prognosis of patients and can promote functional recovery after SCI [44]. Other regulated genes not directly related to the NMDA net includes Cnr1 (Cannabinoid Receptor 1), which is involved in sensory deprivation-induced cortical plasticity by mediating long-term potentiation and depression of synapse strength and the fine-tune of excitatory/inhibitory balance [45].…”