Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Dissertation
Optogenetically mediated neuromodulation paired with exercised based rehabilitation in adult transected rats enhances voluntary control of trunk muscle segments below injury leading to alterations in spinal circuitry
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2019
DOI:
https://doi.org/10.17918/00000089
Abstract
After a complete T9/T10 spinal cord injury (SCI) in adult rats, trunk control becomes very important for postural stability, and crucial for function if stepping of hindlimbs is enabled. We have developed a neuromodulatory technique aimed at promoting plasticity and motor learning in the trunk motor cortex after SCI, by using subthreshold optogenetic stimulation of cortex via virally delivered Channelrhodopsin (ChR2). Virally delivered enhanced yellow fluorescent protein (EYFP) was used as a control. When optogenetically mediated neuromodulation was paired with a 25 day robot assisted rehabilitation paradigm, motor mapping studies revealed a significant increase in cortical representation of trunk muscle segments nominally below the injury in the ChR2+robot rats, both with and without brain derived neurotrophic factor (BDNF) induced spinal stepping, but not in EYFP+robot rats with or without spinal stepping enabled by BDNF. Activation of caudal trunk enabled by these representational changes also caused plastic changes in spinal circuitry below the injury by influencing sensory input and motor output from the spinal cord caudal to injury. Frequency Dependent Depression (FDD) analysis of monosynaptic reflexes is used widely to test spinal excitability. To understand chronic spinal circuit-level changes mediating trunk reflexes below injury in external oblique and longissimus, we implanted a stimulating cuff around the T13 spinal nerve and monitored trunk muscle responses through 13 paired trunk electromyogram electrodes, spaced both above and below injury, over the course of robot rehabilitation. Due to the proximity of the stimulating cuff to the spinal cord, in ipsilateral muscle segments caudal to injury, the motor response and the reflex response overlapped. An artificial neural network was used to separate the two signals. However, we have also discovered contralateral trunk reflex responses of comparable latency, believed to be monosynaptic, which are readily analyzed. In addition, these bilateral trunk reflexes are exhibited at multiple trunk muscle segments both above and below the injury. Neuromodulation of trunk motor cortex exhibited chronic spinal excitability and FDD differences below the injury in non-stepping rats studied and above the injury in stepping rats studied. This study highlights the multisegmental innervation of trunk muscles and the potential of trunk as a rehabilitation target after SCI.
Metrics
43 File views/ downloads
37 Record Views
Details
- Title
- Optogenetically mediated neuromodulation paired with exercised based rehabilitation in adult transected rats enhances voluntary control of trunk muscle segments below injury leading to alterations in spinal circuitry
- Creators
- Kendall Ankudovich Schmidt
- Contributors
- Simon F. Giszter (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 201 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991014695545604721