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Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury.

ABSTRACT: The delivery of brain-controlled neuromodulation therapies during motor rehabilitation may augment recovery from neurological disorders. To test this hypothesis, we conceived a brain-controlled neuromodulation therapy that combines the technical and practical features necessary to be deployed daily during gait rehabilitation. Rats received a severe spinal cord contusion that led to leg paralysis. We engineered a proportional brain-spine interface whereby cortical ensemble activity constantly determines the amplitude of spinal cord stimulation protocols promoting leg flexion during swing. After minimal calibration time and without prior training, this neural bypass enables paralyzed rats to walk overground and adjust foot clearance in order to climb a staircase. Compared to continuous spinal cord stimulation, brain-controlled stimulation accelerates and enhances the long-term recovery of locomotion. These results demonstrate the relevance of brain-controlled neuromodulation therapies to augment recovery from motor disorders, establishing important proofs-of-concept that warrant clinical studies.

SUBMITTER: Bonizzato M

PROVIDER: S-EPMC6070513 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury.

Bonizzato Marco M Pidpruzhnykova Galyna G DiGiovanna Jack J Shkorbatova Polina P Pavlova Natalia N Micera Silvestro S Courtine Grégoire G Courtine Grégoire G

Nature communications 20180801 1

The delivery of brain-controlled neuromodulation therapies during motor rehabilitation may augment recovery from neurological disorders. To test this hypothesis, we conceived a brain-controlled neuromodulation therapy that combines the technical and practical features necessary to be deployed daily during gait rehabilitation. Rats received a severe spinal cord contusion that led to leg paralysis. We engineered a proportional brain-spine interface whereby cortical ensemble activity constantly det ...[more]

PMID: 30068906

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Project description:Serotonin is a monoamine neurotransmitter synthetized in various populations of brainstem neurons. In the spinal cord, descending serotonergic projections regulate postural muscle tone, locomotion and rhythm and coordination of movements via the Central Pattern Generator. Following a spinal cord injury, serotonergic projections to the lumbar spinal cord, where the Central Pattern Generators are located, are interrupted resulting in devastating locomotor impairments and changes in the expression and activation of serotonin and its spinal receptors. The molecular cues that control the precise patterning and targeting of serotonergic inputs onto Central Pattern Generator networks in healthy animals or after injury are still unknown. In our recent research work, we have been particularly interested in Semaphorin7A, which belongs to the Semaphorins family involved in guiding growing axons and controlling plasticity of synaptic connections. In this review, we discuss the role of Semaphorin7A signaling as an important molecular actor that instructs the patterning of serotonin inputs to spinal Central Pattern Generator networks. We show that Semaphorin7A controls the wiring of descending serotonin axons in the spinal cord. Our results reveal that mistargetting of serotonin fibers in the spinal cord is compensated in healthy uninjured Semaphorin7A deficient mice so that their gross locomotion proceeds accurately. We also demonstrate that when the system is challenged with a spinal lesion, the pattern of post-injury serotonin expression is significantly altered in Semaphorin7A deficient mice with specific ectopic targeting of serotonin fibers in the lumbar spinal cord. Compensatory mechanisms in place in uninjured Semaphorin7A deficient mice are lost and injured Semaphorin7A deficient mice exhibit a worsening of their post-injury locomotor abilities. Our findings identify Semaphorin7A as a critical determinant of serotonergic circuit formation in healthy or spinal cord injured mice.

Dataset Information

Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury.

Publications

Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury.

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