This proposal is for a Program Project Grant consisting of four Projects and three Cores. Its overall goal is to investigate interactions betwee spinal circuits and the musculoskeletal system to promote more effective movement-related rehabilitation evaluation and therapeutic strategies. In each of the Projects this objective will b studied in model systems. In Project I (English), the effects of modifying the dosing, pattern, and therapeutic window of treatment with modest daily exercise in the form of treadmill training as a treatment for peripheral nerve injuries will be investigated. In Project II (Prilutsky/Gregor), the role of proprioceptive feedback in shaping functionally appropriate compensations to paralysis of selected muscles and the potential for therapeutic interventions that differentially affect lengh and force dependent feedback from, and mechanical demands on, reinnervated muscles will be studied. In Project III (Nichols), the measurement of limb mechanics will be used to evaluate changes in spinal circuitry resulting from perturbations of musculoskeletal circuits. In Project IV (Wolpaw/Chen), the role of descending neural systems in regulating the interactions of spinal and musculoskeletal circuits will be evaluated. The Projects are supported by Administrative and Technical Cores and a Clinician Scientist Advisory Board. One role of the latter is the implementation of a novel form of two way communication between Project scientists and rehabilitation clinicians. This PPG brings together a team of established scientists from diverse backgrounds, with a common goal to continue to strengthen the science base underlying clinical rehabilitation.

Public Health Relevance

By study of their impact on interactions between neuronal circuitry and the musculoskeletal system, the Projects in this PPG are aimed at enhancing the translational potential of novel treatments and/or evaluation strategies that are applicable to patients with a variety of movement disorders. Their successful completion will serve to strengthen the science base for clinical rehabilitation.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
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Application #
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Nitkin, Ralph M
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Emory University
Anatomy/Cell Biology
Schools of Medicine
United States
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Zhu, Xiya; Ward, Patricia J; English, Arthur W (2016) Selective Requirement for Maintenance of Synaptic Contacts onto Motoneurons by Target-Derived trkB Receptors. Neural Plast 2016:2371893
Gordon, Tessa; English, Arthur W (2016) Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise. Eur J Neurosci 43:336-50
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
Mehta, Ricky; Maas, Huub; Gregor, Robert J et al. (2015) Unexpected Fascicle Length Changes In Denervated Feline Soleus Muscle During Stance Phase Of Walking. Sci Rep 5:17619
Brandt, Jaclyn; Evans, Jonathan T; Mildenhall, Taylor et al. (2015) Delaying the onset of treadmill exercise following peripheral nerve injury has different effects on axon regeneration and motoneuron synaptic plasticity. J Neurophysiol 113:2390-9
Krakowiak, Joey; Liu, Caiyue; Papudesu, Chandana et al. (2015) Neuronal BDNF signaling is necessary for the effects of treadmill exercise on synaptic stripping of axotomized motoneurons. Neural Plast 2015:392591
Farrell, Brad J; Bulgakova, Margarita A; Sirota, Mikhail G et al. (2015) Accurate stepping on a narrow path: mechanics, EMG, and motor cortex activity in the cat. J Neurophysiol 114:2682-702
Lyle, M A; Valero-Cuevas, F J; Gregor, R J et al. (2015) Lower extremity dexterity is associated with agility in adolescent soccer athletes. Scand J Med Sci Sports 25:81-8
Sabatier, Manning J; English, Arthur W (2015) Pathways Mediating Activity-Induced Enhancement of Recovery From Peripheral Nerve Injury. Exerc Sport Sci Rev 43:163-71
Liu, Caiyue; Ward, Patricia J; English, Arthur W (2014) The effects of exercise on synaptic stripping require androgen receptor signaling. PLoS One 9:e98633

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