Throughout life, the nervous system acquires and maintains many different motor skills. These skills depend on complex patterns of activity-dependent plasticity throughout the CNS, from the cortex to the spinal cord. The goal of this research program is to learn how this plasticity can be initiated and guided so as to improve motor function after injury or disease. This goal requires an experimental model based on a simple skill produced by defined and accessible neural circuitry. The spinal stretch reflex (SSR or tendon jerk) satisfies this requirement. Because its spinal pathway is influenced by the brain, monkeys, humans, rats, and mice can gradually increase or decrease the SSR or its electrical analog, the H-reflex, in response to an operant conditioning protocol. By the standard definition of """"""""skill"""""""" as """"""""an adaptive behavior acquired through practice,"""""""" these reflex changes are simple motor skills. This laboratory is exploring the complex patterns of plasticity that underlie these skills, and is learning how reflex conditioning can be used to help restore motor function after injury or disease. Recent work shows that soleus H-reflex conditioning changes soleus behavior during locomotion, and suggests that appropriate conditioning can improve locomotion after a spinal cord injury. Based on this work, this project will test two hypotheses. The first hypothesis is that, in normal rats, the impact of soleus H-reflex conditioning on the soleus locomotor burst induces compensatory changes in the behavior of other muscles that preserve the symmetry of the step cycle, and that these changes in the locomotor behavior of other muscles are due to plasticity in their reflex pathways. The second hypothesis is that, in spinal-cord injured rats with abnormal locomotion, appropriate reflex conditioning can improve the step cycle and that the improvement persists after conditioning ends. These hypotheses will be tested by studying normal rats and rats with well-defined spinal cord injuries before, during, and after up- or down-conditioning of the soleus H-reflex or other spinal reflexes. The impact of conditioning on the locomotor EMG activity and reflexes of soleus and other leg muscles and on the parameters of the step-cycle will be assessed. To evaluate the impact of conditioning on brain and spinal cord interactions, concurrent effects on cortical motor and somatosensory evoked potentials will also be measured. The results should help to clarify the origin and functional impact of the complex plasticity underlying the acquisition and maintenance of motor skills. They should lead to novel methods that use reflex conditioning to improve function after spinal cord injury or other trauma or disease. Reflex conditioning protocols might be designed to target the pathways underlying the particular deficits of each individual, and could thereby complement other more general therapeutic methods such as locomotor training.

Public Health Relevance

Motor skills are acquired and maintained throughout life by changes in the brain and the spinal cord. When skills are impaired by spinal cord injury or other disorders, their restoration requires methods for promoting and guiding these changes. Spinal reflex conditioning is a powerful and precise new therapeutic method that can changespecificnervoussystempathwayssoastohelprestorecomplexmotorskillssuchaslocomotion. The goal of this proposal is to clarify the mechanisms, impact, and long-term benefits of this new therapeutic method.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
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Chen, Daofen
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Wadsworth Center
United States
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Chen, Yi; Chen, Lu; Wang, Yu et al. (2017) Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors. J Neurosci 37:8198-8206
Chen, Xiang Yang; Wang, Yu; Chen, Yi et al. (2016) Ablation of the inferior olive prevents H-reflex down-conditioning in rats. J Neurophysiol 115:1630-6
LaPallo, Brandon K; Wolpaw, Jonathan R; Chen, Xiang Yang et al. (2016) Contribution of the external urethral sphincter to urinary void size in unanesthetized unrestrained rats. Neurourol Urodyn 35:696-702
Thompson, Aiko K; Wolpaw, Jonathan R (2015) Targeted neuroplasticity for rehabilitation. Prog Brain Res 218:157-72
Boulay, Chadwick B; Chen, Xiang Yang; Wolpaw, Jonathan R (2015) Electrocorticographic activity over sensorimotor cortex and motor function in awake behaving rats. J Neurophysiol 113:2232-41
Thompson, Aiko K; Wolpaw, Jonathan R (2015) Restoring walking after spinal cord injury: operant conditioning of spinal reflexes can help. Neuroscientist 21:203-15
Thompson, Aiko K; Wolpaw, Jonathan R (2014) The simplest motor skill: mechanisms and applications of reflex operant conditioning. Exerc Sport Sci Rev 42:82-90
Chen, Yi; Chen, Lu; Liu, Rongliang et al. (2014) Locomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury. J Neurophysiol 111:1249-58
LaPallo, Brandon K; Wolpaw, Jonathan R; Chen, Xiang Yang et al. (2014) Long-term recording of external urethral sphincter EMG activity in unanesthetized, unrestrained rats. Am J Physiol Renal Physiol 307:F485-97
Chen, Yi; Chen, Lu; Wang, Yu et al. (2014) Persistent beneficial impact of H-reflex conditioning in spinal cord-injured rats. J Neurophysiol 112:2374-81

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