Abstract
After complete spinal cord transections that removed all supraspinal inputs in adult rats, combinations of serotonergic agonists and epidural electrical stimulation were able to acutely transform spinal networks from nonfunctional to highly functional and adaptive states as early as 1 week after injury. Using kinematics, physiological and anatomical analyses, we found that these interventions could recruit specific populations of spinal circuits, refine their control via sensory input and functionally remodel these locomotor pathways when combined with training. The emergence of these new functional states enabled full weight-bearing treadmill locomotion in paralyzed rats that was almost indistinguishable from voluntary stepping. We propose that, in the absence of supraspinal input, spinal locomotion can emerge from a combination of central pattern-generating capability and the ability of these spinal circuits to use sensory afferent input to control stepping. These findings provide a strategy by which individuals with spinal cord injuries could regain substantial levels of motor control.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Hydroxy-2-(di-n-propylamino)tetralin / therapeutic use
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Analysis of Variance
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Animals
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Biomechanical Phenomena / physiology
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Brain / pathology
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Disease Models, Animal
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Electric Stimulation / methods
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Electromyography / methods
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Female
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Gait / drug effects
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Gait / physiology
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Hindlimb / physiopathology
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Locomotion / drug effects
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Locomotion / physiology
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Motor Activity / drug effects
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Motor Activity / physiology
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiopathology
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Nerve Net / drug effects
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Nerve Net / physiology*
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Neural Pathways / drug effects
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Neural Pathways / physiopathology*
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Oncogene Proteins v-fos / metabolism
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Physical Conditioning, Animal
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Principal Component Analysis
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Quipazine / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Recovery of Function / drug effects
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Recovery of Function / physiology*
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Reflex / physiology
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Serotonin Receptor Agonists / therapeutic use
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Spinal Cord Injuries* / pathology
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Spinal Cord Injuries* / physiopathology
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Spinal Cord Injuries* / therapy
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Time Factors
Substances
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Oncogene Proteins v-fos
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Serotonin Receptor Agonists
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Quipazine
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8-Hydroxy-2-(di-n-propylamino)tetralin