Functional Connectivity of the Mesolimbic System with the Motor Cortex Supporting Functional Recovery after Spinal Cord Injury

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

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Trunk sensory and motor cortex is preferentially integrated with hindlimb sensory information that supports trunk stabilization

10.1101/2020.08.31.272583 ◽

2020 ◽

Author(s):

Bharadwaj Nandakumar ◽

Gary H. Blumenthal ◽

Francois Philippe Pauzin ◽

Karen A. Moxon

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Cortex ◽

Postural Control ◽

Functional Recovery ◽

Sensorimotor Integration ◽

Cortical Reorganization ◽

Sensory Cortex ◽

Proprioceptive Information ◽

Cord Injury

AbstractSensorimotor integration in the trunk system has been poorly studied despite its importance for examining functional recovery after neurological injury or disease. Here, we mapped the relationship between thoracic dorsal root ganglia and trunk sensory cortex (S1) to create a detailed map of the extent and internal organization of trunk primary sensory cortex, and trunk primary motor cortex (M1) and showed that both cortices are somatotopically complex structures that are larger than previously described. Surprisingly, projections from trunk S1 to trunk M1 were not anatomically organized. We found relatively weak sensorimotor integration between trunk M1 and S1 and between trunk M1 and forelimb S1 compared to extensive integration between trunk M1 and hindlimb S1 and M1. This strong trunk/hindlimb connection was identified for high intensity stimuli that activated proprioceptive pathways. To assess the implication of this integration, the responses in sensorimotor cortex were examined during a postural control task and supported sensorimotor integration between hindlimb sensory and lower trunk motor cortex. Together, these data suggest that trunk M1 is guided predominately by hindlimb proprioceptive information that reached the cortex directly via the thalamus. This unique sensorimotor integration suggests an essential role for the trunk system in postural control, and its consideration could be important for understanding studies regarding recovery of function after spinal cord injury.SignificanceThis work identifies extensive sensorimotor integration between trunk and hindlimb cortices, demonstrating that sensorimotor integration is an operational mode of the trunk cortex in intact animals. The functional role of this integration was demonstrated for postural control when the animal was subjected to lateral tilts. Furthermore, these results provide insight into cortical reorganization after spinal cord injury making clear that sensorimotor integration after SCI is an attempt to restore sensorimotor integration that existed in the intact system. These results could be used to tailor rehabilitative strategies to optimize sensorimotor integration for functional recovery.

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Faculty Opinions recommendation of Ryk controls remapping of motor cortex during functional recovery after spinal cord injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726277217.793520581 ◽

2016 ◽

Author(s):

Martin Schwab

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Cortex ◽

Functional Recovery ◽

Cord Injury

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Ryk controls remapping of motor cortex during functional recovery after spinal cord injury

Nature Neuroscience ◽

10.1038/nn.4282 ◽

2016 ◽

Vol 19 (5) ◽

pp. 697-705 ◽

Cited By ~ 43

Author(s):

Edmund R Hollis ◽

Nao Ishiko ◽

Ting Yu ◽

Chin-Chun Lu ◽

Ariela Haimovich ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Cortex ◽

Functional Recovery ◽

Cord Injury

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Optogenetic Neuronal Stimulation Promotes Functional Recovery After Spinal Cord Injury

Frontiers in Neuroscience ◽

10.3389/fnins.2021.640255 ◽

2021 ◽

Vol 15 ◽

Author(s):

Wei-wei Deng ◽

Guang-yan Wu ◽

Ling-xia Min ◽

Zhou Feng ◽

Hui Chen ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Cortex ◽

Functional Recovery ◽

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Cell Types ◽

Treatment Method ◽

Cord Injury ◽

Tissue Recovery

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.

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