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REMOTE DISRUPTION OF FUNCTION, PLASTICITY, AND LEARNING IN LOCOMOTOR NETWORKS AFTER SPINAL CORD INJURY

Hansen, Christopher Nelson
http://rave.ohiolink.edu/etdc/view?acc_num=osu1385716231

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Neuroscience Graduate Studies Program.
Spinal cord injury (SCI) creates a diverse range of functional outcomes. Impaired locomotion may be the most noticeable and debilitating consequence. Locomotor patterns result from a dynamic interaction between sensory and motor systems in the lumbar enlargement of the spinal cord. After SCI, conflicting cellular and molecular processes initiate along the neuroaxis that may secondarily jeopardize function, plasticity, and learning within locomotor networks. Thus, we used a standardized thoracic contusion to replicate human pathology and identified behavioral, physiological, cellular, and molecular effects in rat and mouse models. Specifically, our goal was to identify kinematic and neuromotor changes during locomotion, evaluate the role of axonal sparing on remote spinal learning, and identify mechanisms of neuroinflammation in the lumbar enlargement that may prevent locomotor plasticity after SCI. Eccentric muscle actions require precise segmental integration of sensory and motor signals. Eccentric motor control is predominant during the yield (E2) phase of locomotion. To identify kinematic and neuromotor changes in E2, we used a mild SCI that allows almost complete functional recovery. Remaining deficits included a caudal shift in locomotor subphases that accompanied a marked reduction in eccentric angular excursions and intralimb coordination. Underlying these metrics, we found distinct bursting impairments in the semitendinosus. Phasic impairments during the eccentric activation of the semitendinosus improved over time and predicted the extent of recovery. Our findings suggest that maladaptive integration of descending and afferent signals limit central pattern generator-directed locomotion after SCI. Axonal sparing after SCI facilitates plasticity rostral and caudal to the lesion. To evaluate the role of axonal sparing on remote lumbar plasticity, we examined learning in isolated lumbar segments early (7d) and late (42d) after SCI. A proof of principle design compared rats that recovered with or without sparing. Early after SCI, learning was impaired regardless of sparing. Alternatively, axonal sparing during recovery allowed near-normal learning late after SCI. To determine if eccentric task-specific training differentially regulates spinal learning, we delivered flat or downhill treadmill training late after recovery from incomplete SCI (34-41d). Downhill treadmill training improved recovery and central learning. This work identifies a time dependent interaction between spared axonal systems and task-specific plasticity in locomotor networks. To determine if remote mechanisms of neuroinflammation impede locomotor plasticity, we conducted a series of experiments in wild type (WT) and genetically engineered (KO) mice. Within 24h in WT mice, resident microglia displayed an inflammatory phenotype alongside increased expression of pro-gelatinase, MMP-3. By 7 and 9d, MMP-9 and TNFa reached significant elevations alongside persistent activation of resident microglia. In MMP-9 null (KO) mice, inflammatory signaling was restored to homeostatic levels. Finally, we examined recovery after early (2-9d) or late (35-42d) treadmill training delivered in WT and MMP-9 KO mice. We found that early training resulted in robust locomotor recovery in MMP-9 KO mice that was retained 4-weeks after the intervention ended. Late training failed to promote recovery in either groups. With these findings, we identified a robust period of locomotor plasticity early after thoracic SCI that is blunted by remote neuroinflammation in locomotor networks.
D. Michele Basso, PT, EdD (Advisor)
178 p.
Neurosciences
Spinal Cord Injury, Locomotion, Neuroinflammation

Recommended Citations

Citations

  • Hansen, C. N. (2013). REMOTE DISRUPTION OF FUNCTION, PLASTICITY, AND LEARNING IN LOCOMOTOR NETWORKS AFTER SPINAL CORD INJURY [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1385716231

    APA Style (7th edition)

  • Hansen, Christopher. REMOTE DISRUPTION OF FUNCTION, PLASTICITY, AND LEARNING IN LOCOMOTOR NETWORKS AFTER SPINAL CORD INJURY. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1385716231.

    MLA Style (8th edition)

  • Hansen, Christopher. "REMOTE DISRUPTION OF FUNCTION, PLASTICITY, AND LEARNING IN LOCOMOTOR NETWORKS AFTER SPINAL CORD INJURY." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1385716231

    Chicago Manual of Style (17th edition)

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© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.