B. Abstract Damage to peripheral nerves as a result of trauma is a frequent event that incapacitates hundreds of thousands of people in the US and around the world. Despite a long history of research into the mechanisms of peripheral nerve injury and regeneration, outcomes of nerve repair are still unsatisfactory especially in patients with complete transection of mixed nerves at proximal locations. Likely reasons for poor recovery after peripheral nerve injury in these cases are that feedback signals from regenerated afferents in self-reinnen/ated muscles do not elicit reflex responses in the motoneurons (loss of proprioceptive input to the central nervous system) and that activity of proximal two-joint muscles is heavily dependent on proprioceptive feedback. The goal of this proposal is to develop a basis for novel therapeutic interventions to improve functional recovery after nerve injury by investigating the sensory control of proximal two-joint muscles.
In Aim 1, we will determine the effects of lost proprioceptive input after self-reinnervation of cat proximal one-joint and two-joint muscles on whole body locomotion. We will test specific predictions about locomotor changes in activity of multiple hindlimb muscles and whole-body mechanics resulting from reinnervation of quadriceps and different heads of the biceps femoris muscles.
In Aim 2, we will investigate sensory mechanisms of functionally appropriate motor compensations that occur after denegeration of selected hindlimb muscles. By sequentially reinnervating all major synergists at a joint, we will determine the extent to which proprioceptive input from selected intact synergists contributes to functionally appropriate compensatory responses to muscle denervation.
In Aim 3, we will determine the effects of varying onset times of locomotor training on recovery of locomotor patterns and reflex responses of self-reinnervated proximal hindlimb muscles. The studied therapeutic interventions will include locomotor conditions with increased demands on proprioceptive input or mechanical output from the affected muscles.

Public Health Relevance

The results of the proposed study will enhance our understanding of sensory control of proximal two-joint muscles, adaptive changes after nerve injury and therapeutic intervenfions aimed at recovery of proprioceptive input. We anticipate that this new knowledge will contribute to the formulation of novel treatment strategies for patients with injured peripheral nerves.

National Institute of Health (NIH)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
United States
Zip Code
English, Arthur W; Wilhelm, Jennifer C; Ward, Patricia J (2014) Exercise, neurotrophins, and axon regeneration in the PNS. Physiology (Bethesda) 29:437-45
Lyle, Mark A; Valero-Cuevas, Francisco J; Gregor, Robert J et al. (2014) Control of dynamic foot-ground interactions in male and female soccer athletes: females exhibit reduced dexterity and higher limb stiffness during landing. J Biomech 47:512-7
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
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
Farrell, Brad J; Bulgakova, Margarita A; Beloozerova, Irina N et al. (2014) Body stability and muscle and motor cortex activity during walking with wide stance. J Neurophysiol 112:504-24
Klishko, Alexander N; Farrell, Bradley J; Beloozerova, Irina N et al. (2014) Stabilization of cat paw trajectory during locomotion. J Neurophysiol 112:1376-91
Liu, Caiyue; Ward, Patricia J; English, Arthur W (2014) The effects of exercise on synaptic stripping require androgen receptor signaling. PLoS One 9:e98633
Honeycutt, Claire F; Nichols, T Richard (2014) The mechanical actions of muscles predict the direction of muscle activation during postural perturbations in the cat hindlimb. J Neurophysiol 111:900-7
Boeltz, Tiffany; Ireland, Meredith; Mathis, Kristin et al. (2013) Effects of treadmill training on functional recovery following peripheral nerve injury in rats. J Neurophysiol 109:2645-57
Burkholder, Thomas J; van Antwerp, Keith W (2013) Practical limits on muscle synergy identification by non-negative matrix factorization in systems with mechanical constraints. Med Biol Eng Comput 51:187-96

Showing the most recent 10 out of 63 publications