Recovery of hindlimb motor function after complete mid-thoracic spinal cord transection is highly dependent on routinely practiced motor skills. Development of use-dependent therapeutic procedures to facilitate recovery of motor function following injury has advanced to testing stages with human patients, but little is known about the adaptations in the spinal cord that can account for this recovery. In the present study, behavioral, physiological and biochemical adaptations that occur as a result of the hindlimbs of neonatal transected rats acquiring the ability to step or stand will be examined. Motion analysis and electromyograms will be used to quantify the activation of motor pools. We will test whether improvements in stepping and standing are associated with a loss of glycinergic and GABAergic inhibition in spinal pathways. Biochemical adaptations in the glycinergic and GABAergic systems that occur in lumbar spinal cord and/or dorsal root immunohistochemistry. Because limitations in flexion and/or extension of the hindlimb can limit the ability to step or to stand, the identification of specific biochemical changes associated with flexor and extensor neural pathways would represent an important advance toward understanding the neural substrates of motor recovery following spinal cord injury. To address this issue dorsal root ganglion neurons and motor neurons of extensor and flexor pathways will be identified using retrograde labeling of the soleus and tibialis anterior, respectively. Therefore, we will be able to identify changes in GABAergic and glycinergic properties of pathways associated with primarily flexion versus extension in transected rats that have acquired skills that require the use of flexors and extensors in different ways, i.e. standing versus stepping. Results from the proposed studies will provide a better understanding of how spinal neural pathways that control posture and locomotion are influenced by use-dependent mechanisms. These results will provide a framework around which strategies for pharmacologically modulating these tasks can be developed.

Project Start
2000-05-01
Project End
2001-04-30
Budget Start
Budget End
Support Year
19
Fiscal Year
2000
Total Cost
$231,922
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Duru, Paul O; Tillakaratne, Niranjala J K; Kim, Jung A et al. (2015) Spinal neuronal activation during locomotor-like activity enabled by epidural stimulation and 5-hydroxytryptamine agonists in spinal rats. J Neurosci Res 93:1229-39
Tillakaratne, Niranjala J K; Duru, Paul; Fujino, Hidemi et al. (2014) Identification of interneurons activated at different inclines during treadmill locomotion in adult rats. J Neurosci Res 92:1714-22
Terson de Paleville, Daniela; McKay, William; Aslan, Sevda et al. (2013) Locomotor step training with body weight support improves respiratory motor function in individuals with chronic spinal cord injury. Respir Physiol Neurobiol 189:491-7
Johnson, Will L; Jindrich, Devin L; Roy, Roland R et al. (2012) Quantitative metrics of spinal cord injury recovery in the rat using motion capture, electromyography and ground reaction force measurement. J Neurosci Methods 206:65-72
Harkema, Susan; Behrman, Andrea; Barbeau, Hugues (2012) Evidence-based therapy for recovery of function after spinal cord injury. Handb Clin Neurol 109:259-74
Johnson, Will L; Jindrich, Devin L; Zhong, Hui et al. (2011) Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles. IEEE Trans Biomed Eng 58:3328-38
Roy, Roland R; Zhong, Hui; Monti, Ryan J et al. (2011) Selectively reshaping a muscle phenotype: functional overload of cat plantaris. Muscle Nerve 43:489-99
Ichiyama, Ronaldo M; Broman, Jonas; Roy, Roland R et al. (2011) Locomotor training maintains normal inhibitory influence on both alpha- and gamma-motoneurons after neonatal spinal cord transection. J Neurosci 31:26-33
Joseph, M Selvan; Bilousova, Tina; Zdunowski, Sharon et al. (2011) Transgenic Mice With Enhanced Neuronal Major Histocompatibility Complex Class I Expression Recover Locomotor Function Better After Spinal Cord Injury. J Neurosci 89:365-372
Lee, Yu-Shang; Zdunowski, Sharon; Edgerton, V Reggie et al. (2010) Improvement of gait patterns in step-trained, complete spinal cord-transected rats treated with a peripheral nerve graft and acidic fibroblast growth factor. Exp Neurol 224:429-37

Showing the most recent 10 out of 221 publications